@article{gawthrop_energy-based_2014, title = {Energy-based analysis of biochemical cycles using bond graphs}, volume = {470}, copyright = {© 2014 The Author(s) Published by the Royal Society. All rights reserved.}, issn = {1364-5021, 1471-2946}, url = {http://rspb.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/470/2171/20140459}, doi = {10.1098/rspa.2014.0459}, abstract = {Thermodynamic aspects of chemical reactions have a long history in the physical chemistry literature. In particular, biochemical cycles require a source of energy to function. However, although fundamental, the role of chemical potential and Gibb's free energy in the analysis of biochemical systems is often overlooked leading to models which are physically impossible. The bond graph approach was developed for modelling engineering systems, where energy generation, storage and transmission are fundamental. The method focuses on how power flows between components and how energy is stored, transmitted or dissipated within components. Based on the early ideas of network thermodynamics, we have applied this approach to biochemical systems to generate models which automatically obey the laws of thermodynamics. We illustrate the method with examples of biochemical cycles. We have found that thermodynamically compliant models of simple biochemical cycles can easily be developed using this approach. In particular, both stoichiometric information and simulation models can be developed directly from the bond graph. Furthermore, model reduction and approximation while retaining structural and thermodynamic properties is facilitated. Because the bond graph approach is also modular and scaleable, we believe that it provides a secure foundation for building thermodynamically compliant models of large biochemical networks.}, language = {en}, number = {2171}, urldate = {2015-07-02}, journal = {Proceedings of the Royal Society of London A: Mathematical, Physical and Engineering Sciences}, author = {Gawthrop, Peter J. and Crampin, Edmund J.}, month = nov, year = {2014}, keywords = {Bond graphs}, pages = {20140459}, file = {Gawthrop_Crampin (2014) - Energy-based analysis of biochemical cycles using bond graphs.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DHKA578N\\Gawthrop_Crampin (2014) - Energy-based analysis of biochemical cycles using bond graphs.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MX5834AC\\20140459.html:text/html} } @article{feinberg_chemical_1972, title = {On chemical kinetics of a certain class}, volume = {46}, issn = {0003-9527, 1432-0673}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF00251866}, doi = {10.1007/BF00251866}, language = {en}, number = {1}, urldate = {2015-08-04}, journal = {Archive for Rational Mechanics and Analysis}, author = {Feinberg, Martin}, month = jan, year = {1972}, keywords = {Electromagnetism, Optics and Lasers, Fluids, Mathematical and Computational Physics, Mechanics, Nonlinear Dynamics, Complex Systems, Chaos, Neural Networks, Physical biochemistry}, pages = {1--41}, file = {Feinberg (1972) - On chemical kinetics of a certain class.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VXRK4WX6\\Feinberg (1972) - On chemical kinetics of a certain class.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RJBQRGJV\\10.html:text/html} } @article{gunawardena_time-scale_2014, title = {Time-scale separation – {Michaelis} and {Menten}'s old idea, still bearing fruit}, volume = {281}, copyright = {© 2013 FEBS}, issn = {1742-4658}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/febs.12532/abstract}, doi = {10.1111/febs.12532}, abstract = {Michaelis and Menten introduced to biochemistry the idea of time-scale separation, in which part of a system is assumed to be operating sufficiently fast compared to the rest so that it may be taken to have reached a steady state. This allows, in principle, the fast components to be eliminated, resulting in a simplified description of the system's behaviour. Similar ideas have been widely used in different areas of biology, including enzyme kinetics, protein allostery, receptor pharmacology, gene regulation and post-translational modification. However, the methods used have been independent and ad hoc. In the present study, we review the use of time-scale separation as a means to simplify the description of molecular complexity and discuss recent work setting out a single framework that unifies these separate calculations. The framework offers new capabilities for mathematical analysis and helps to do justice to Michaelis and Menten's insights about individual enzymes in the context of multi-enzyme biological systems.}, language = {en}, number = {2}, urldate = {2015-08-05}, journal = {FEBS Journal}, author = {Gunawardena, Jeremy}, month = jan, year = {2014}, keywords = {algebraic elimination, linear framework, Matrix-Tree Theorem, Physical biochemistry, quasi-steady state assumption, time-scale separation}, pages = {473--488}, file = {Gunawardena (2014) - Time-scale separation – Michaelis and Menten's old idea, still bearing fruit.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JWSTE7VN\\Gunawardena (2014) - Time-scale separation – Michaelis and Menten's old idea, still bearing fruit.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UMVIEFVH\\full.html:text/html} } @article{tran_thermodynamic_2009, title = {A {Thermodynamic} {Model} of the {Cardiac} {Sarcoplasmic}/{Endoplasmic} {Ca}$^{2+}$ ({SERCA}) {Pump}}, volume = {96}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349509002124}, doi = {10.1016/j.bpj.2008.11.045}, abstract = {We present a biophysically based kinetic model of the cardiac SERCA pump that consolidates a range of experimental data into a consistent and thermodynamically constrained framework. The SERCA model consists of a number of sub-states with partial reactions that are sensitive to Ca2+ and pH, and to the metabolites MgATP, MgADP, and Pi. Optimization of model parameters to fit experimental data favors a fully cooperative Ca2+-binding mechanism and predicts a Ca2+/H+ counter-transport stoichiometry of 2. Moreover, the order of binding of the partial reactions, particularly the binding of MgATP, proves to be a strong determinant of the ability of the model to fit the data. A thermodynamic investigation of the model indicates that the binding of MgATP has a large inhibitory effect on the maximal reverse rate of the pump. The model is suitable for integrating into whole-cell models of cardiac electrophysiology and Ca2+ dynamics to simulate the effects on the cell of compromised metabolism arising in ischemia and hypoxia.}, number = {5}, urldate = {2015-07-02}, journal = {Biophysical Journal}, author = {Tran, Kenneth and Smith, Nicolas P. and Loiselle, Denis S. and Crampin, Edmund J.}, month = mar, year = {2009}, keywords = {SERCA}, pages = {2029--2042}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EIIJMDBK\\S0006349509002124.html:text/html;Tran et al (2009) - A Thermodynamic Model of the Cardiac Sarcoplasmic-Endoplasmic Ca2+ (SERCA) Pump.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FKN737HT\\Tran et al (2009) - A Thermodynamic Model of the Cardiac Sarcoplasmic-Endoplasmic Ca2+ (SERCA) Pump.pdf:application/pdf} } @article{smith_development_2004, series = {Modelling {Cellular} and {Tissue} {Function}}, title = {Development of models of active ion transport for whole-cell modelling: cardiac sodium–potassium pump as a case study}, volume = {85}, issn = {0079-6107}, shorttitle = {Development of models of active ion transport for whole-cell modelling}, url = {http://www.sciencedirect.com/science/article/pii/S0079610704000215}, doi = {10.1016/j.pbiomolbio.2004.01.010}, abstract = {This study presents a method for the reduction of biophysically-based kinetic models for the active transport of ions. A lumping scheme is presented which exploits the differences in timescales associated with fast and slow transitions between model states, while maintaining the thermodynamic properties of the model. The goal of this approach is to contribute to modelling of the effects of disturbances to metabolism, associated with ischaemic heart disease, on cardiac cell function. The approach is illustrated for the sodium-potassium pump in the myocyte. The lumping scheme is applied to produce a 4-state representation from the detailed 15-state model of Läuger and Apell, Eur. Biophys. J. 13 (1986) 309, for which the principles of free energy transduction are used to link the free energy released from ATP hydrolysis (ΔGATP) to the transition rates between states of the model. An iterative minimisation algorithm is implemented to determine the transition rate parameters based on the model fit to experimental data. Finally, the relationship between ΔGATP and pump cycling direction is investigated and compared with recent experimental findings.}, number = {2–3}, urldate = {2015-07-03}, journal = {Progress in Biophysics and Molecular Biology}, author = {Smith, N. P. and Crampin, E. J.}, month = jun, year = {2004}, keywords = {Cardiac myocyte metabolism, Free energy transduction, Mathematical model, Na/K-ATPase, Sodium–potassium pump}, pages = {387--405}, file = {Smith_Crampin (2004) - Development of models of active ion transport for whole-cell modelling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EZJDXQXV\\Smith_Crampin (2004) - Development of models of active ion transport for whole-cell modelling.pdf:application/pdf} } @article{gawthrop_bond-graph_2007, title = {Bond-graph modeling}, volume = {27}, issn = {1066-033X}, doi = {10.1109/MCS.2007.338279}, abstract = {The bond-graph method is a graphical approach to modeling in which component energy ports are connected by bonds that specify the transfer of energy between system components. Power, the rate of energy transport between components, is the universal currency of physical systems. Bond graphs are inherently energy based and thus related to other energy-based methods, including dissipative systems and port-Hamiltonians. This article has presented an introduction to bond graphs for control engineers. Although the notation can initially appear daunting, the bond graph method is firmly grounded in the familiar concepts of energy and power. The essential element to be grasped is that bonds represent power transactions between components}, number = {2}, journal = {IEEE Control Systems}, author = {Gawthrop, P.J. and Bevan, G.P.}, month = apr, year = {2007}, keywords = {Aerodynamics, Analog computers, bond-graph method, bond graphs, Bonding, component energy ports, control system analysis, dissipative systems, energy transport, Fluid dynamics, Fluid flow control, graphical approach, Kelvin, Maxwell equations, Nonlinear equations, port-Hamiltonians, Power system modeling, power transactions, Resistance heating}, pages = {24--45}, file = {Gawthrop_Bevan (2007) - Bond-graph modeling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\62MVFVNR\\Gawthrop_Bevan (2007) - Bond-graph modeling.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JCCTPMSZ\\abs_all.html:text/html} } @article{gawthrop_supplementary_2015, title = {Supplementary material for “{Energy}-based {Analysis} of {Biochemical} {Cycles} using {Bond} {Graphs}”}, issn = {1364-5021, 1471-2946}, url = {http://rspa.royalsocietypublishing.org/content/suppl/2014/09/24/rspa.2014.0459.DC1}, language = {en}, urldate = {2015-07-06}, journal = {Proceedings of the Royal Society of London A: Mathematical, Physical and Engineering Sciences}, author = {Gawthrop, Peter J. and Crampin, Edmund J.}, month = jul, year = {2015}, keywords = {Bond graphs}, file = {(2015) - Data Supplement.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TQHJ6Z6J\\(2015) - Data Supplement.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6FTABW6H\\rspa.2014.0459.html:text/html} } @article{hodgkin_propagation_1952, title = {Propagation of {Electrical} {Signals} {Along} {Giant} {Nerve} {Fibres}}, volume = {140}, copyright = {Copyright © 1952 The Royal Society}, issn = {0080-4649}, url = {http://www.jstor.org/stable/82686}, number = {899}, urldate = {2015-07-07}, journal = {Proceedings of the Royal Society of London. Series B, Biological Sciences}, author = {Hodgkin, A. L. and Huxley, A. F.}, month = oct, year = {1952}, keywords = {Neuron}, pages = {177--183}, file = {Hodgkin_Huxley (1952) - Propagation of Electrical Signals Along Giant Nerve Fibres.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\N7Q5VH4G\\Hodgkin_Huxley (1952) - Propagation of Electrical Signals Along Giant Nerve Fibres.pdf:application/pdf} } @article{gawthrop_mtt:_1994, title = {{MTT}: {Model} transformation tools}, volume = {27}, shorttitle = {{MTT}}, url = {http://mtt.sf.net/doc/mtt.pdf}, urldate = {2015-07-08}, journal = {SIMULATION SERIES}, author = {Gawthrop, Peter J.}, year = {1994}, keywords = {Bond graphs, Software}, pages = {197--197}, file = {Gawthrop (1994) - MTT.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UP9FJXQC\\Gawthrop (1994) - MTT.pdf:application/pdf} } @book{cellier_continuous_1991, address = {New York}, title = {Continuous system modeling}, isbn = {978-0-387-97502-3 978-3-540-97502-1}, publisher = {Springer-Verlag}, author = {Cellier, François E.}, year = {1991}, keywords = {Bond graphs, Computer simulation, Mathematical models, Simulation methods}, file = {Cellier (1991) - Continuous system modeling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DC99F5RE\\Cellier (1991) - Continuous system modeling.pdf:application/pdf} } @article{hasenstaub_metabolic_2010, title = {Metabolic cost as a unifying principle governing neuronal biophysics}, volume = {107}, issn = {0027-8424, 1091-6490}, url = {http://www.pnas.org/content/107/27/12329}, doi = {10.1073/pnas.0914886107}, abstract = {The brain contains an astonishing diversity of neurons, each expressing only one set of ion channels out of the billions of potential channel combinations. Simple organizing principles are required for us to make sense of this abundance of possibilities and wealth of related data. We suggest that energy minimization subject to functional constraints may be one such unifying principle. We compared the energy needed to produce action potentials singly and in trains for a wide range of channel densities and kinetic parameters and examined which combinations of parameters maximized spiking function while minimizing energetic cost. We confirmed these results for sodium channels using a dynamic current clamp in neocortical fast spiking interneurons. We find further evidence supporting this hypothesis in a wide range of other neurons from several species and conclude that the ion channels in these neurons minimize energy expenditure in their normal range of spiking.}, language = {en}, number = {27}, urldate = {2015-07-09}, journal = {Proceedings of the National Academy of Sciences}, author = {Hasenstaub, Andrea and Otte, Stephani and Callaway, Edward and Sejnowski, Terrence J.}, month = jul, year = {2010}, pmid = {20616090}, keywords = {action potential, energy, evolution, ion channel, Neuron, optimization}, pages = {12329--12334}, file = {Hasenstaub et al (2010) - Metabolic cost as a unifying principle governing neuronal biophysics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SNBMB9RG\\Hasenstaub et al (2010) - Metabolic cost as a unifying principle governing neuronal biophysics.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WEDHP2Z8\\12329.html:text/html} } @article{gutenkunst_universally_2007, title = {Universally {Sloppy} {Parameter} {Sensitivities} in {Systems} {Biology} {Models}}, volume = {3}, url = {http://dx.plos.org/10.1371/journal.pcbi.0030189}, doi = {10.1371/journal.pcbi.0030189}, abstract = {Author Summary{\textless}p{\textgreater}Dynamic systems biology models typically involve many kinetic parameters, the quantitative determination of which has been a serious obstacle to using these models. Previous work showed for a particular model that useful predictions could be extracted from a fit long before the experimental data constrained the parameters, even to within orders of magnitude. This was attributed to a “sloppy” pattern in the model's parameter sensitivities; the sensitivity eigenvalues were roughly evenly spaced over many decades. Consequently, the model behavior depended effectively on only a few “stiff” parameter combinations. Here we study the converse problem, showing that direct parameter measurements are very inefficient at constraining the model's behavior. To yield effective predictions, such measurements must be very precise and complete; even a single imprecise parameter often destroys predictivity. We also show here that the characteristic sloppy eigenvalue pattern is reproduced in 16 other diverse models from the systems biology literature. The apparent universality of sloppiness suggests that predictions from most models will be very fragile to single uncertain parameters and that collective parameters fits can often yield tight predictions with loose parameters. Together these results argue that focusing on parameter values may be a very inefficient route to useful models.{\textless}/p{\textgreater}{\textless}/sec{\textgreater}}, number = {10}, urldate = {2015-08-27}, journal = {PLoS Comput Biol}, author = {Gutenkunst, Ryan N and Waterfall, Joshua J and Casey, Fergal P and Brown, Kevin S and Myers, Christopher R and Sethna, James P}, month = oct, year = {2007}, keywords = {Physical biochemistry}, pages = {e189}, file = {Gutenkunst et al (2007) - Universally Sloppy Parameter Sensitivities in Systems Biology Models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QUU6AR4G\\Gutenkunst et al (2007) - Universally Sloppy Parameter Sensitivities in Systems Biology Models.pdf:application/pdf} } @article{van_der_schaft_mathematical_2013, title = {On the {Mathematical} {Structure} of {Balanced} {Chemical} {Reaction} {Networks} {Governed} by {Mass} {Action} {Kinetics}}, volume = {73}, issn = {0036-1399}, url = {http://epubs.siam.org.ezp.lib.unimelb.edu.au/doi/abs/10.1137/11085431X}, doi = {10.1137/11085431X}, abstract = {Motivated by recent progress on the interplay between graph theory, dynamics, and systems theory, we revisit the analysis of chemical reaction networks described by mass action kinetics. For reaction networks possessing a thermodynamic equilibrium we derive a compact formulation exhibiting at the same time the structure of the complex graph and the stoichiometry of the network, and which admits a direct thermodynamical interpretation. This formulation allows us to easily characterize the set of positive equilibria and their stability properties. Furthermore, we develop a framework for interconnection of chemical reaction networks, and we discuss how the formulation leads to a new approach for model reduction., Motivated by recent progress on the interplay between graph theory, dynamics, and systems theory, we revisit the analysis of chemical reaction networks described by mass action kinetics. For reaction networks possessing a thermodynamic equilibrium we derive a compact formulation exhibiting at the same time the structure of the complex graph and the stoichiometry of the network, and which admits a direct thermodynamical interpretation. This formulation allows us to easily characterize the set of positive equilibria and their stability properties. Furthermore, we develop a framework for interconnection of chemical reaction networks, and we discuss how the formulation leads to a new approach for model reduction.}, number = {2}, urldate = {2015-09-02}, journal = {SIAM Journal on Applied Mathematics}, author = {van der Schaft, A. and Rao, S. and Jayawardhana, B.}, month = jan, year = {2013}, keywords = {Physical biochemistry}, pages = {953--973}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KUJE5FFQ\\11085431X.html:text/html;van der Schaft et al (2013) - On the Mathematical Structure of Balanced Chemical Reaction Networks Governed.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EGPGQ9PA\\van der Schaft et al (2013) - On the Mathematical Structure of Balanced Chemical Reaction Networks Governed.pdf:application/pdf} } @article{hodgkin_quantitative_1952, title = {A quantitative description of membrane current and its application to conduction and excitation in nerve}, volume = {117}, copyright = {© 1952 The Physiological Society}, issn = {1469-7793}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/jphysiol.1952.sp004764/abstract}, doi = {10.1113/jphysiol.1952.sp004764}, language = {en}, number = {4}, urldate = {2015-07-08}, journal = {The Journal of Physiology}, author = {Hodgkin, A. L. and Huxley, A. F.}, month = aug, year = {1952}, keywords = {Neuron}, pages = {500--544}, file = {Hodgkin_Huxley (1952) - A quantitative description of membrane current and its application to.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TDJGMSVN\\Hodgkin_Huxley (1952) - A quantitative description of membrane current and its application to.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ENC4JIEK\\abstract.html:text/html} } @article{gawthrop_causal_1992, title = {Causal augmentation of bond graphs with algebraic loops}, volume = {329}, issn = {0016-0032}, url = {http://www.sciencedirect.com/science/article/pii/001600329290035F}, doi = {10.1016/0016-0032(92)90035-F}, abstract = {An algorithm for the causal augmentation of bond graphs with algebraic loops is given. Unlike previous algorithms, this involves bond graph—rather than equation— manipulation. A number of illustrative examples are given.}, number = {2}, urldate = {2016-05-02}, journal = {Journal of the Franklin Institute}, author = {Gawthrop, P. J. and Smith, L.}, month = mar, year = {1992}, pages = {291--303}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KAJ3QWKZ\\001600329290035F.html:text/html} } @article{lambeth_computational_2002, title = {A {Computational} {Model} for {Glycogenolysis} in {Skeletal} {Muscle}}, volume = {30}, issn = {0090-6964, 1573-9686}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1114/1.1492813}, doi = {10.1114/1.1492813}, abstract = {A dynamic model of the glycogenolytic pathway to lactate in skeletal muscle was constructed with mammalian kinetic parameters obtained from the literature. Energetic buffers relevant to muscle were included. The model design features stoichiometric constraints, mass balance, and fully reversible thermodynamics as defined by the Haldane relation. We employed a novel method of validating the thermodynamics of the model by allowing the closed system to come to equilibrium; the combined mass action ratio of the pathway equaled the product of the individual enzymes' equilibrium constants. Adding features physiologically relevant to muscle—a fixed glycogen concentration, efflux of lactate, and coupling to an ATPase—allowed for a steady-state flux far from equilibrium. The main result of our analysis is that coupling of the glycogenolytic network to the ATPase transformed the entire complex into an ATPase driven system. This steady-state system was most sensitive to the external ATPase activity and not to internal pathway mechanisms. The control distribution among the internal pathway enzymes—although small compared to control by ATPase—depended on the flux level and fraction of glycogen phosphorylase a. This model of muscle glycogenolysis thus has unique features compared to models developed for other cell types. © 2002 Biomedical Engineering Society. PAC2002: 8719Ff, 8239Fk, 8718Bb, 8714Ee}, language = {en}, number = {6}, urldate = {2015-07-15}, journal = {Annals of Biomedical Engineering}, author = {Lambeth, Melissa J. and Kushmerick, Martin J.}, month = jun, year = {2002}, keywords = {Biochemistry, general, Biomedical Engineering, Biophysics/Biomedical Physics, Enzyme kinetics, Flux analysis, Mechanics, Metabolism, Vibration, Dynamical Systems, Control}, pages = {808--827}, file = {Lambeth_Kushmerick (2002) - A Computational Model for Glycogenolysis in Skeletal Muscle.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QBZMJ5WP\\Lambeth_Kushmerick (2002) - A Computational Model for Glycogenolysis in Skeletal Muscle.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\M2M5AMF6\\1.html:text/html} } @article{james_generalised_1978, title = {The {Generalised} {Inverse}}, volume = {62}, copyright = {Copyright © 1978 The Mathematical Association}, issn = {0025-5572}, url = {http://www.jstor.org/stable/3617665}, doi = {10.2307/3617665}, number = {420}, urldate = {2015-09-02}, journal = {The Mathematical Gazette}, author = {James, M.}, month = jun, year = {1978}, pages = {109--114}, file = {James (1978) - The Generalised Inverse.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BGZN5TAC\\James (1978) - The Generalised Inverse.pdf:application/pdf} } @article{hill_studies_1966, title = {Studies in irreversible thermodynamics {IV}. diagrammatic representation of steady state fluxes for unimolecular systems}, volume = {10}, issn = {0022-5193}, url = {http://www.sciencedirect.com/science/article/pii/0022519366901378}, doi = {10.1016/0022-5193(66)90137-8}, abstract = {We consider a system of equivalent, independent units each of which can exist in n states. Transitions between pairs of states follow unimolecular kinetics. Certain models for membrane transport provide examples. The states and allowed transitions, for any given model, can be represented by a basic diagram. Rate constants for the transitions are generally chosen so that the system reaches a non-equilibrium steady state at t = ∞. The population of the different states at steady state can be calculated by a diagram method. Similarly, diagrams may be used to find the steady state net flux between pairs of states. In particular, fluxes can be related to possible cycles in the basic diagram. The difference in products of rate constants around a cycle in opposite directions is related to a thermodynamic force. Hence flux-force equations follow from the diagram approach. These equations are applicable to arbitrary steady states; linear terms exhibit reciprocal relations. Near equilibrium, the conventional flux-force equations of irreversible thermodynamics obtain. The reciprocal relations are compounded from individual cycle reciprocal relations. The latter follow directly from the properties of cycles.}, number = {3}, urldate = {2015-07-21}, journal = {Journal of Theoretical Biology}, author = {Hill, Terrell L.}, month = apr, year = {1966}, keywords = {Physical biochemistry}, pages = {442--459}, file = {Hill (1966) - Studies in irreversible thermodynamics IV.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UWAS945C\\Hill (1966) - Studies in irreversible thermodynamics IV.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2BMGZEJX\\0022519366901378.html:text/html} } @article{lauger_microscopic_1986, title = {A microscopic model for the current-voltage behaviour of the {Na},{K}-pump}, volume = {13}, issn = {0175-7571, 1432-1017}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF00254213}, doi = {10.1007/BF00254213}, abstract = {The current voltage characteristic of the Na, K pump is described on the basis of a modified Post-Albers cycle. The voltage dependence of the rate constants is derived from the elementary chargetranslocations associated with the single reaction steps. Charge displacements result from movements of the sodium- or potassium-loaded binding sites, as well as from motions of polar groups in the pump molecule. If part of the transmembrane voltage drops between the alkali-ion binding sites and the aqueous solution, the binding constants become voltage-dependent. Depending on the values of the microscopic parameters, the current-voltage characteristic may assume a variety of different shapes. Saturating behaviour results when one or more voltage-independent reaction steps become rate limiting. Non-monotonic current-voltage curves exhibiting regions of negative pump conductance are predicted when, at least in one of the transitions, charge is moved against the direction of overall charge-translocation. The theoretical predictions are compared with recent experimental studies of voltage-dependent pump currents.}, language = {en}, number = {5}, urldate = {2015-07-22}, journal = {European Biophysics Journal}, author = {Läuger, P. and Apell, H.-J.}, month = jun, year = {1986}, keywords = {active transport, Animal Physiology, Biochemistry, general, Biophysics/Biomedical Physics, Cell Biology, current-voltage behaviour, electrogenic transport, Na, K-pump, Neurobiology, Plant Physiology, Post-Albers scheme}, pages = {309--321}, file = {Läuger_Apell (1986) - A microscopic model for the current-voltage behaviour of the Na,K-pump.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R5S4EZCU\\Läuger_Apell (1986) - A microscopic model for the current-voltage behaviour of the Na,K-pump.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2KAZWB6G\\BF00254213.html:text/html} } @book{keener_mathematical_2009, address = {New York, NY}, series = {Interdisciplinary {Applied} {Mathematics}}, title = {Mathematical {Physiology}}, volume = {8/1}, isbn = {978-0-387-75846-6 978-0-387-75847-3}, urldate = {2015-07-23}, publisher = {Springer New York}, author = {Keener, James and Sneyd, James}, editor = {Antman, S.S. and Marsden, J.E. and Sirovich, L.}, year = {2009}, file = {Keener_Sneyd (2009) - Mathematical Physiology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CZB6VHHD\\Keener_Sneyd (2009) - Mathematical Physiology.pdf:application/pdf} } @book{hill_free_1989, title = {Free {Energy} {Transduction} and {Biochemical} {Cycle} {Kinetics}. [electronic resource]}, isbn = {978-1-4612-3558-3}, abstract = {Summary: With this brief and updated textbook, Dr. Hill wants to explain in much simpler language than was possible in his prior research monographs the theory of free energy transfer in biology, and finally make it accessible to students and investigators entering this field. It is designed for an upper-level class in biochemistry or biophysics and can also be used for self-study.}, publisher = {New York, NY : Springer New York, 1989.}, author = {Hill, Terrell L.}, year = {1989}, keywords = {Actin-myosin, Biochemistry, Electronic books, Physical biochemistry, Physics}, file = {Hill (1989) - Free Energy Transduction and Biochemical Cycle Kinetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HI7GCSN9\\Hill (1989) - Free Energy Transduction and Biochemical Cycle Kinetics.pdf:application/pdf} } @article{liebermeister_modular_2010, title = {Modular rate laws for enzymatic reactions: thermodynamics, elasticities and implementation}, volume = {26}, issn = {1367-4803, 1460-2059}, shorttitle = {Modular rate laws for enzymatic reactions}, url = {http://bioinformatics.oxfordjournals.org/content/26/12/1528}, doi = {10.1093/bioinformatics/btq141}, abstract = {Motivation: Standard rate laws are a key requisite for systematically turning metabolic networks into kinetic models. They should provide simple, general and biochemically plausible formulae for reaction velocities and reaction elasticities. At the same time, they need to respect thermodynamic relations between the kinetic constants and the metabolic fluxes and concentrations. Results: We present a family of reversible rate laws for reactions with arbitrary stoichiometries and various types of regulation, including mass–action, Michaelis–Menten and uni–uni reversible Hill kinetics as special cases. With a thermodynamically safe parameterization of these rate laws, parameter sets obtained by model fitting, sampling or optimization are guaranteed to lead to consistent chemical equilibrium states. A reformulation using saturation values yields simple formulae for rates and elasticities, which can be easily adjusted to the given stationary flux distributions. Furthermore, this formulation highlights the role of chemical potential differences as thermodynamic driving forces. We compare the modular rate laws to the thermodynamic–kinetic modelling formalism and discuss a simplified rate law in which the reaction rate directly depends on the reaction affinity. For automatic handling of modular rate laws, we propose a standard syntax and semantic annotations for the Systems Biology Markup Language. Availability: An online tool for inserting the rate laws into SBML models is freely available at www.semanticsbml.org Contact: wolfram.liebermeister@biologie.hu-berlin.de Supplementary Information: Supplementary data are available at Bioinformatics online.}, language = {en}, number = {12}, urldate = {2015-08-10}, journal = {Bioinformatics}, author = {Liebermeister, Wolfram and Uhlendorf, Jannis and Klipp, Edda}, month = jun, year = {2010}, pmid = {20385728}, keywords = {Physical biochemistry}, pages = {1528--1534}, file = {Liebermeister et al (2010) - Modular rate laws for enzymatic reactions.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XD7NRDX6\\Liebermeister et al (2010) - Modular rate laws for enzymatic reactions.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7HZEHDD4\\1528.html:text/html} } @book{atkins_physical_2006, address = {Oxford, UK : New York}, title = {Physical chemistry for the life sciences}, isbn = {978-0-7167-8628-3 978-0-19-928095-7}, publisher = {Oxford University Press ; W.H. Freeman}, author = {Atkins, P. W. and De Paula, Julio}, year = {2006}, keywords = {Chemistry, Physical and theoretical, Life sciences, Physical biochemistry}, file = {Atkins_De Paula (2006) - Physical chemistry for the life sciences.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\K7PRXBXI\\Atkins_De Paula (2006) - Physical chemistry for the life sciences.pdf:application/pdf} } @article{polettini_irreversible_2014, title = {Irreversible thermodynamics of open chemical networks. {I}. {Emergent} cycles and broken conservation laws}, volume = {141}, issn = {0021-9606, 1089-7690}, url = {http://scitation.aip.org.ezp.lib.unimelb.edu.au/content/aip/journal/jcp/141/2/10.1063/1.4886396}, doi = {10.1063/1.4886396}, abstract = {In this paper and Paper II, we outline a general framework for the thermodynamic description of open chemical reaction networks, with special regard to metabolic networks regulating cellular physiology and biochemical functions. We first introduce closed networks “in a box”, whose thermodynamics is subjected to strict physical constraints: the mass-action law, elementarity of processes, and detailed balance. We further digress on the role of solvents and on the seemingly unacknowledged property of network independence of free energy landscapes. We then open the system by assuming that the concentrations of certain substrate species (the chemostats) are fixed, whether because promptly regulated by the environment via contact with reservoirs, or because nearly constant in a time window. As a result, the system is driven out of equilibrium. A rich algebraic and topological structure ensues in the network of internal species: Emergent irreversible cycles are associated with nonvanishing affinities, whose symmetries are dictated by the breakage of conservation laws. These central results are resumed in the relation a + b = s Y between the number of fundamental affinities a, that of broken conservation laws b and the number of chemostats s Y . We decompose the steady state entropy production rate in terms of fundamental fluxes and affinities in the spirit of Schnakenberg\'s theory of network thermodynamics, paving the way for the forthcoming treatment of the linear regime, of efficiency and tight coupling, of free energy transduction, and of thermodynamic constraints for network reconstruction.}, number = {2}, urldate = {2015-08-24}, journal = {The Journal of Chemical Physics}, author = {Polettini, Matteo and Esposito, Massimiliano}, month = jul, year = {2014}, keywords = {Chemical potential, Chemical reactions, Conservation laws, Electron paramagnetic resonance spectroscopy, Free energy, Physical biochemistry}, pages = {024117}, file = {Polettini_Esposito (2014) - Irreversible thermodynamics of open chemical networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WHMKBA55\\Polettini_Esposito (2014) - Irreversible thermodynamics of open chemical networks.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\972TQ6RR\\1.html:text/html} } @article{hung_moore-penrose_1975, title = {The {Moore}-{Penrose} inverse of a partitioned matrix}, volume = {11}, issn = {0024-3795}, url = {http://www.sciencedirect.com/science/article/pii/0024379575901184}, doi = {10.1016/0024-3795(75)90118-4}, abstract = {We give an explicit formula for the Moore-Penrose inverse of an m × n partitioned matrix M = ( A D B C ) , and then derive some representations, which are simpler in form when conditions are placed on the blocks of the partitioning of the matrix.}, number = {1}, urldate = {2015-09-03}, journal = {Linear Algebra and its Applications}, author = {Hung, Ching-hsiang and Markham, T. L.}, year = {1975}, pages = {73--86}, file = {Hung_Markham (1975) - The Moore-Penrose inverse of a partitioned matrix.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KZV46HFR\\Hung_Markham (1975) - The Moore-Penrose inverse of a partitioned matrix.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IMAAW2VN\\0024379575901184.html:text/html} } @book{gawthrop_metamodelling:_1996, address = {London, New York}, series = {Prentice {Hall} international series in systems and control engineering}, title = {Metamodelling: for bond graphs and dynamic systems}, isbn = {978-0-13-489824-7}, shorttitle = {Metamodelling}, publisher = {Prentice Hall}, author = {Gawthrop, Peter and Smith, Lorcan}, year = {1996}, keywords = {Bond graphs, Computer simulation, Mathematical models}, file = {GawSmi96.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XN3JXMAQ\\GawSmi96.pdf:application/pdf} } @article{hasdemir_validation_2015, title = {Validation and selection of {ODE} based systems biology models: how to arrive at more reliable decisions}, volume = {9}, copyright = {2015 Hasdemir et al.}, issn = {1752-0509}, shorttitle = {Validation and selection of {ODE} based systems biology models}, url = {http://www.biomedcentral.com/1752-0509/9/32/abstract}, doi = {10.1186/s12918-015-0180-0}, abstract = {Most ordinary differential equation (ODE) based modeling studies in systems biology involve a hold-out validation step for model validation. In this framework a pre-determined part of the data is used as validation data and, therefore it is not used for estimating the parameters of the model. The model is assumed to be validated if the model predictions on the validation dataset show good agreement with the data. Model selection between alternative model structures can also be performed in the same setting, based on the predictive power of the model structures on the validation dataset. However, drawbacks associated with this approach are usually under-estimated.}, language = {en}, number = {1}, urldate = {2015-09-30}, journal = {BMC Systems Biology}, author = {Hasdemir, Dicle and Hoefsloot, Huub CJ and Smilde, Age K.}, month = jul, year = {2015}, pmid = {26152206}, keywords = {Cross validation, Differential equations, Hold-out validation, Kinetic models, Model selection, Model validation, ODE}, pages = {32}, file = {Hasdemir et al (2015) - Validation and selection of ODE based systems biology models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IC3SVPTJ\\Hasdemir et al (2015) - Validation and selection of ODE based systems biology models.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\58QB5NJW\\32.html:text/html} } @book{turanyi_analysis_2014, address = {Berlin, Heidelberg}, title = {Analysis of {Kinetic} {Reaction} {Mechanisms}}, isbn = {978-3-662-44561-7 978-3-662-44562-4}, url = {http://link.springer.com/10.1007/978-3-662-44562-4}, language = {en}, urldate = {2015-10-09}, publisher = {Springer Berlin Heidelberg}, author = {Turányi, Tamás and Tomlin, Alison S.}, year = {2014}, keywords = {Physical biochemistry}, file = {Analysis of Reaction Mechanisms.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PZP5UB47\\Analysis of Reaction Mechanisms.pdf:application/pdf} } @article{beard_thermodynamic_2004, title = {Thermodynamic constraints for biochemical networks}, volume = {228}, issn = {0022-5193}, url = {http://www.sciencedirect.com/science/article/pii/S0022519304000372}, doi = {10.1016/j.jtbi.2004.01.008}, abstract = {The constraint-based approach to analysis of biochemical systems has emerged as a useful tool for rational metabolic engineering. Flux balance analysis (FBA) is based on the constraint of mass conservation; energy balance analysis (EBA) is based on non-equilibrium thermodynamics. The power of these approaches lies in the fact that the constraints are based on physical laws, and do not make use of unknown parameters. Here, we show that the network structure (i.e. the stoichiometric matrix) alone provides a system of constraints on the fluxes in a biochemical network which are feasible according to both mass balance and the laws of thermodynamics. A realistic example shows that these constraints can be sufficient for deriving unambiguous, biologically meaningful results. The thermodynamic constraints are obtained by comparing of the sign pattern of the flux vector to the sign patterns of the cycles of the internal cycle space via connection between stoichiometric network theory (SNT) and the mathematical theory of oriented matroids.}, number = {3}, urldate = {2015-10-20}, journal = {Journal of Theoretical Biology}, author = {Beard, Daniel A. and Babson, Eric and Curtis, Edward and Qian, Hong}, month = jun, year = {2004}, keywords = {Biochemical network, Matroid, Metabolic flux analysis, Nonequilibrium thermodynamics, Physical biochemistry}, pages = {327--333}, file = {Beard et al (2004) - Thermodynamic constraints for biochemical networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HN3T2QR9\\Beard et al (2004) - Thermodynamic constraints for biochemical networks.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VSQUBMSB\\S0022519304000372.html:text/html} } @article{onsager_reciprocal_1931, title = {Reciprocal {Relations} in {Irreversible} {Processes}. {I}.}, volume = {37}, url = {http://link.aps.org/doi/10.1103/PhysRev.37.405}, doi = {10.1103/PhysRev.37.405}, abstract = {Examples of coupled irreversible processes like the thermoelectric phenomena, the transference phenomena in electrolytes and heat conduction in an anisotropic medium are considered. For certain cases of such interaction reciprocal relations have been deduced by earlier writers, e.g., Thomson's theory of thermoelectric phenomena and Helmholtz' theory for the e.m.f. of electrolytic cells with liquid junction. These earlier derivations may be classed as quasi-thermodynamic; in fact, Thomson himself pointed out that his argument was incomplete, and that his relation ought to be established on an experimental basis. A general class of such relations will be derived by a new theoretical treatment from the principle of microscopic reversibility. (§§1-2.) The analogy with a chemical monomolecular triangle reaction is discussed; in this case a a simple kinetic consideration assuming microscopic reversibility yields a reciprocal relation that is not necessary for fulfilling the requirements of thermodynamics (§3). Reciprocal relations for heat conduction in an anisotropic medium are derived from the assumption of microscopic reversibility, applied to fluctuations. (§4.) The reciprocal relations can be expressed in terms of a potential, the dissipation-function. Lord Rayleigh's "principle of the least dissipation of energy" is generalized to include the case of anisotropic heat conduction. A further generalization is announced. (§5.) The conditions for stationary flow are formulated; the connection with earlier quasi-thermodynamic theories is discussed. (§6.) The principle of dynamical reversibility does not apply when (external) magnetic fields or Coriolis forces are present, and the reciprocal relations break down. (§7.)}, number = {4}, urldate = {2015-10-23}, journal = {Physical Review}, author = {Onsager, Lars}, month = feb, year = {1931}, keywords = {Thermodynamics}, pages = {405--426}, file = {APS Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HC3GP6AU\\PhysRev.37.html:text/html;Onsager (1931) - Reciprocal Relations in Irreversible Processes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SHS9D82H\\Onsager (1931) - Reciprocal Relations in Irreversible Processes.pdf:application/pdf} } @article{chellaboina_modeling_2009, title = {Modeling and analysis of mass-action kinetics}, volume = {29}, issn = {1066-033X}, doi = {10.1109/MCS.2009.932926}, abstract = {Mass-action kinetics are used in chemistry and chemical engineering to describe the dynamics of systems of chemical reactions, that is, reaction networks. These models are a special form of compartmental systems, which involve mass- and energy-balance relations. Aside from their role in chemical engineering applications, mass-action kinetics have numerous analytical properties that are of inherent interest from a dynamical systems perspective. Because of physical considerations, however, mass- action kinetics have special properties, such as nonnegative solutions, that are useful for analyzing their behavior. With this motivation in mind, this article has several objectives. First, a general construction of the kinetic equations based on the reaction laws is provided in a state-space form. Next, the nonnegativity of solutions to the kinetic equations is considered. The realizability problem, which is concerned with the inverse problem of constructing a reaction network having specified essentially nonnegative dynamics, is also considered. In particular, an explicit construction of a reaction network for essentially nonnegative polynomial dynamics involving a scalar state is provided. Next, the reducibility of the kinetic equations is considered as well as the stability of the equilibria of the kinetic equations. Lyapunov methods are applied to the kinetic equations, and semistability is guaranteed through the convergence to a Lyapunov- stable equilibrium that depends on the initial concentrations. Semistability is the appropriate notion of stability for compartmental systems in general, and reaction networks in particular, where the limiting concentration maybe nonzero and may depend on the initial concentrations. Finally, the zero deficiency result for mass-action kinetics in standard matrix terminology is presented and semistability is proven.}, number = {4}, journal = {IEEE Control Systems}, author = {Chellaboina, V. and Bhat, S. and Haddad, M.M. and Bernstein, D.S.}, month = aug, year = {2009}, keywords = {Chemical analysis, Chemical engineering, Chemistry, Convergence, dynamical systems, energy-balance relations, Equations, essentially nonnegative polynomial dynamics, Inverse problems, kinetic equation equilibrium stability, kinetic equation reducibility, kinetic equations, Kinetic theory, Lyapunov method, Lyapunov methods, Lyapunov stable equilibrium, mass-action kinetics analysis, mass-action kinetics modeling, mass-action kinetics zero deficiency result, mass-balance relations, network theory (graphs), nonlinear dynamical systems, Nonlinear equations, nonnegative dynamics, nonnegative solutions, Physical biochemistry, polynomials, reaction kinetics theory, reaction laws, reaction network construction inverse problem, reaction network dynamics, realizability problem, semistability, solution nonnegativity, stability, state space form}, pages = {60--78}, file = {Chellaboina et al (2009) - Modeling and analysis of mass-action kinetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\J6BF9HGK\\Chellaboina et al (2009) - Modeling and analysis of mass-action kinetics.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CW3NX4H2\\abs_all.html:text/html} } @article{cropp_modelling_2013, series = {Advances in {Marine} {Ecosystem} {Modelling} {Research} {III}}, title = {Modelling plankton ecosystems and the {Library} of {Lotka}}, volume = {125}, issn = {0924-7963}, url = {http://www.sciencedirect.com/science/article/pii/S0924796312001662}, doi = {10.1016/j.jmarsys.2012.08.005}, abstract = {Predicting how change will impact ecosystems requires the development of complex models. The complexity of ecosystem models often defies the power of analytical mathematical techniques so they are commonly solved using computers. A problem with this approach is the difficulty in assessing the credibility of model simulation results. We apply ecological axioms to the construction of complex model ecologies. The axioms ensure realistic ecological properties and internal consistency of a broad class of models that encompass many theoretical and applied models. A key new analytical result for our dynamical systems in ecospace is that extinctions can be studied without knowledge of either interior equilibrium points or their stability. By looking only at boundary extinction points we can immediately comment on the extinction behaviour without solving for any of the dynamics. This is a striking simplification, and even holds when the dynamics are chaotic. We demonstrate the approach by constructing three plankton ecosystem models that we designed to have specific properties and show that the effect of change on plankton blooms and/or extinctions depends on the properties of the model chosen for the simulation.}, urldate = {2015-11-11}, journal = {Journal of Marine Systems}, author = {Cropp, Roger and Norbury, John}, month = sep, year = {2013}, keywords = {Climate change, Consistent normal ecologies, Dynamical system, Ecosystem model, Emergent properties, Library of Lotka}, pages = {3--13}, file = {Cropp_Norbury (2013) - Modelling plankton ecosystems and the Library of Lotka.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IXTAW325\\Cropp_Norbury (2013) - Modelling plankton ecosystems and the Library of Lotka.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7U6D5HEB\\S0924796312001662.html:text/html} } @article{oster_network_1973, title = {Network thermodynamics: dynamic modelling of biophysical systems}, volume = {6}, issn = {1469-8994}, shorttitle = {Network thermodynamics}, url = {http://journals.cambridge.org/article_S0033583500000081}, doi = {10.1017/S0033583500000081}, abstract = {The success of equilibrium thermodynamics in describing static phenomena has inspired many attempts to develop a rigorous thermodynamics of rate processes.}, number = {01}, urldate = {2015-11-12}, journal = {Quarterly Reviews of Biophysics}, author = {Oster, George F. and Perelson, Alan S. and Katchalsky, Aharon}, month = feb, year = {1973}, keywords = {Physical biochemistry}, pages = {1--134}, file = {Cambridge Journals Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SK5NG6RB\\displayAbstract.html:text/html;Oster et al (1973) - Network thermodynamics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MIIISUGZ\\Oster et al (1973) - Network thermodynamics.pdf:application/pdf} } @article{periasamy_serca_2007, title = {{SERCA} pump isoforms: {Their} role in calcium transport and disease}, volume = {35}, copyright = {Copyright © 2007 Wiley Periodicals, Inc.}, issn = {1097-4598}, shorttitle = {{SERCA} pump isoforms}, url = {http://onlinelibrary.wiley.com/doi/10.1002/mus.20745/abstract}, doi = {10.1002/mus.20745}, abstract = {The sarcoendoplasmic reticulum (SR) calcium transport ATPase (SERCA) is a pump that transports calcium ions from the cytoplasm into the SR. It is present in both animal and plant cells, although knowledge of SERCA in the latter is scant. The pump shares the catalytic properties of ion-motive ATPases of the P-type family, but has distinctive regulation properties. The SERCA pump is encoded by a family of three genes, SERCA1, 2, and 3, that are highly conserved but localized on different chromosomes. The SERCA isoform diversity is dramatically enhanced by alternative splicing of the transcripts, occurring mainly at the COOH-terminal. At present, more than 10 different SERCA isoforms have been detected at the protein level. These isoforms exhibit both tissue and developmental specificity, suggesting that they contribute to unique physiological properties of the tissue in which they are expressed. The function of the SERCA pump is modulated by the endogenous molecules phospholamban (PLB) and sarcolipin (SLN), expressed in cardiac and skeletal muscles. The mechanism of action of PLB on SERCA is well characterized, whereas that of SLN is only beginning to be understood. Because the SERCA pump plays a major role in muscle contraction, a number of investigations have focused on understanding its role in cardiac and skeletal muscle disease. These studies document that SERCA pump expression and activity are decreased in aging and in a variety of pathophysiological conditions including heart failure. Recently, SERCA pump gene transfer was shown to be effective in restoring contractile function in failing heart muscle, thus emphasizing its importance in muscle physiology and its potential use as a therapeutic agent. Muscle Nerve, 2007}, language = {en}, number = {4}, urldate = {2015-11-11}, journal = {Muscle \& Nerve}, author = {Periasamy, Muthu and Kalyanasundaram, Anuradha}, month = apr, year = {2007}, keywords = {calcium, endoplasmic reticulum, phospholamban, sarcolipin, sarcoplasmic reticulum, SERCA}, pages = {430--442}, file = {Periasamy_Kalyanasundaram (2007) - SERCA pump isoforms.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SPSF66FU\\Periasamy_Kalyanasundaram (2007) - SERCA pump isoforms.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4N6ARG4U\\abstract.html:text/html} } @article{gunawardena_biology_2013, title = {Biology is more theoretical than physics}, volume = {24}, issn = {1059-1524, 1939-4586}, url = {http://www.molbiolcell.org/content/24/12/1827}, doi = {10.1091/mbc.E12-03-0227}, abstract = {The word “theory” is used in at least two senses—to denote a body of widely accepted laws or principles, as in “Darwinian theory” or “quantum theory,” and to suggest a speculative hypothesis, often relying on mathematical analysis, that has not been experimentally confirmed. It is often said that there is no place for the second kind of theory in biology and that biology is not theoretical but based on interpretation of data. Here, ideas from a previous essay are expanded upon to suggest, to the contrary, that the second kind of theory has always played a critical role and that biology, therefore, is a good deal more theoretical than physics.}, language = {en}, number = {12}, urldate = {2015-11-12}, journal = {Molecular Biology of the Cell}, author = {Gunawardena, Jeremy}, month = jun, year = {2013}, pmid = {23765269}, pages = {1827--1829}, file = {Gunawardena (2013) - Biology is more theoretical than physics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VCHV4WTE\\Gunawardena (2013) - Biology is more theoretical than physics.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BVGH5CK4\\1827.html:text/html} } @article{ramnanan_regulation_2010, title = {Regulation of sarcoendoplasmic reticulum {Ca}2+-{ATPase} ({SERCA}) in turtle muscle and liver during acute exposure to anoxia}, volume = {213}, copyright = {© 2010.}, issn = {0022-0949, 1477-9145}, url = {http://jeb.biologists.org/content/213/1/17}, doi = {10.1242/jeb.036087}, language = {en}, number = {1}, urldate = {2015-11-18}, journal = {Journal of Experimental Biology}, author = {Ramnanan, C. J. and McMullen, D. C. and Bielecki, A. and Storey, K. B.}, month = jan, year = {2010}, pmid = {20008357}, keywords = {SERCA}, pages = {17--25}, file = {Ramnanan et al (2010) - Regulation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) in turtle muscle.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EN733ZZE\\Ramnanan et al (2010) - Regulation of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA) in turtle muscle.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\THXFISTC\\17.html:text/html} } @article{drager_sbmlsqueezer_2015, title = {{SBMLsqueezer} 2: context-sensitive creation of kinetic equations in biochemical networks}, volume = {9}, copyright = {2015 Dräger et al.}, issn = {1752-0509}, shorttitle = {{SBMLsqueezer} 2}, url = {http://www.biomedcentral.com/1752-0509/9/68/abstract}, doi = {10.1186/s12918-015-0212-9}, abstract = {The size and complexity of published biochemical network reconstructions are steadily increasing, expanding the potential scale of derived computational models. However, the construction of large biochemical network models is a laborious and error-prone task. Automated methods have simplified the network reconstruction process, but building kinetic models for these systems is still a manually intensive task. Appropriate kinetic equations, based upon reaction rate laws, must be constructed and parameterized for each reaction. The complex test-and-evaluation cycles that can be involved during kinetic model construction would thus benefit from automated methods for rate law assignment.}, language = {en}, number = {1}, urldate = {2015-11-25}, journal = {BMC Systems Biology}, author = {Dräger, Andreas and Zielinski, Daniel C. and Keller, Roland and Rall, Matthias and Eichner, Johannes and Palsson, Bernhard O. and Zell, Andreas}, month = oct, year = {2015}, pmid = {26452770}, keywords = {Biological networks, Information extraction, Mathematical modeling, Metabolic engineering, Physical biochemistry, Regulatory networks, Software engineering}, pages = {68}, file = {Dräger et al (2015) - SBMLsqueezer 2.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IPC8WVAH\\Dräger et al (2015) - SBMLsqueezer 2.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\A69AFS3Z\\68.html:text/html} } @article{wray_sarcoplasmic_2010, title = {Sarcoplasmic {Reticulum} {Function} in {Smooth} {Muscle}}, volume = {90}, copyright = {Copyright © 2010 the American Physiological Society}, issn = {0031-9333, 1522-1210}, url = {http://physrev.physiology.org/content/90/1/113}, doi = {10.1152/physrev.00018.2008}, abstract = {The sarcoplasmic reticulum (SR) of smooth muscles presents many intriguing facets and questions concerning its roles, especially as these change with development, disease, and modulation of physiological activity. The SR's function was originally perceived to be synthetic and then that of a Ca store for the contractile proteins, acting as a Ca amplification mechanism as it does in striated muscles. Gradually, as investigators have struggled to find a convincing role for Ca-induced Ca release in many smooth muscles, a role in controlling excitability has emerged. This is the Ca spark/spontaneous transient outward current coupling mechanism which reduces excitability and limits contraction. Release of SR Ca occurs in response to inositol 1,4,5-trisphosphate, Ca, and nicotinic acid adenine dinucleotide phosphate, and depletion of SR Ca can initiate Ca entry, the mechanism of which is being investigated but seems to involve Stim and Orai as found in nonexcitable cells. The contribution of the elemental Ca signals from the SR, sparks and puffs, to global Ca signals, i.e., Ca waves and oscillations, is becoming clearer but is far from established. The dynamics of SR Ca release and uptake mechanisms are reviewed along with the control of luminal Ca. We review the growing list of the SR's functions that still includes Ca storage, contraction, and relaxation but has been expanded to encompass Ca homeostasis, generating local and global Ca signals, and contributing to cellular microdomains and signaling in other organelles, including mitochondria, lysosomes, and the nucleus. For an integrated approach, a review of aspects of the SR in health and disease and during development and aging are also included. While the sheer versatility of smooth muscle makes it foolish to have a “one model fits all” approach to this subject, we have tried to synthesize conclusions wherever possible.}, language = {en}, number = {1}, urldate = {2015-11-25}, journal = {Physiological Reviews}, author = {Wray, Susan and Burdyga, Theodor}, month = jan, year = {2010}, pmid = {20086075}, keywords = {SERCA}, pages = {113--178}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CQKTKAB3\\113.html:text/html;Wray_Burdyga (2010) - Sarcoplasmic Reticulum Function in Smooth Muscle.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DVWWWSG9\\Wray_Burdyga (2010) - Sarcoplasmic Reticulum Function in Smooth Muscle.pdf:application/pdf} } @article{resendis-antonio_modeling_2015, series = {Cancer modeling and network {biologyAccelerating} toward personalized medicine}, title = {Modeling metabolism: {A} window toward a comprehensive interpretation of networks in cancer}, volume = {30}, issn = {1044-579X}, shorttitle = {Modeling metabolism}, url = {http://www.sciencedirect.com/science/article/pii/S1044579X14000510}, doi = {10.1016/j.semcancer.2014.04.003}, abstract = {Given the multi-factorial nature of cancer, uncovering its metabolic alterations and evaluating their implications is a major challenge in biomedical sciences that will help in the optimal design of personalized treatments. The advance of high-throughput technologies opens an invaluable opportunity to monitor the activity at diverse biological levels and elucidate how cancer originates, evolves and responds under drug treatments. To this end, researchers are confronted with two fundamental questions: how to interpret high-throughput data and how this information can contribute to the development of personalized treatment in patients. A variety of schemes in systems biology have been suggested to characterize the phenotypic states associated with cancer by utilizing computational modeling and high-throughput data. These theoretical schemes are distinguished by the level of complexity of the biological mechanisms that they represent and by the computational approaches used to simulate them. Notably, these theoretical approaches have provided a proper framework to explore some distinctive metabolic mechanisms observed in cancer cells such as the Warburg effect. In this review, we focus on presenting a general view of some of these approaches whose application and integration will be crucial in the transition from local to global conclusions in cancer studies. We are convinced that multidisciplinary approaches are required to construct the bases of an integrative and personalized medicine, which has been and remains a fundamental task in the medicine of this century.}, urldate = {2015-11-25}, journal = {Seminars in Cancer Biology}, author = {Resendis-Antonio, Osbaldo and González-Torres, Carolina and Jaime-Muñoz, Gustavo and Hernandez-Patiño, Claudia Erika and Salgado-Muñoz, Carlos Felipe}, month = feb, year = {2015}, keywords = {Cancer metabolism, Mathematical models, Metabolism, P4 medicine, Systems biology: Constraint-based modeling}, pages = {79--87}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2EB3CCW9\\S1044579X14000510.html:text/html} } @article{fearnley_calcium_2011, title = {Calcium {Signaling} in {Cardiac} {Myocytes}}, volume = {3}, issn = {, 1943-0264}, url = {http://cshperspectives.cshlp.org/content/3/11/a004242}, doi = {10.1101/cshperspect.a004242}, abstract = {Calcium (Ca2+) is a critical regulator of cardiac myocyte function. Principally, Ca2+ is the link between the electrical signals that pervade the heart and contraction of the myocytes to propel blood. In addition, Ca2+ controls numerous other myocyte activities, including gene transcription. Cardiac Ca2+ signaling essentially relies on a few critical molecular players—ryanodine receptors, voltage-operated Ca2+ channels, and Ca2+ pumps/transporters. These moieties are responsible for generating Ca2+ signals upon cellular depolarization, recovery of Ca2+ signals following cellular contraction, and setting basal conditions. Whereas these are the central players underlying cardiac Ca2+ fluxes, networks of signaling mechanisms and accessory proteins impart complex regulation on cardiac Ca2+ signals. Subtle changes in components of the cardiac Ca2+ signaling machinery, albeit through mutation, disease, or chronic alteration of hemodynamic demand, can have profound consequences for the function and phenotype of myocytes. Here, we discuss mechanisms underlying Ca2+ signaling in ventricular and atrial myocytes. In particular, we describe the roles and regulation of key participants involved in Ca2+ signal generation and reversal.}, language = {en}, number = {11}, urldate = {2015-11-26}, journal = {Cold Spring Harbor Perspectives in Biology}, author = {Fearnley, Claire J. and Roderick, H. Llewelyn and Bootman, Martin D.}, month = nov, year = {2011}, pmid = {21875987}, keywords = {Calcium signalling, SERCA}, pages = {a004242}, file = {Fearnley et al (2011) - Calcium Signaling in Cardiac Myocytes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\E8H8SZ2C\\Fearnley et al (2011) - Calcium Signaling in Cardiac Myocytes.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C3SGFNHQ\\a004242.html:text/html} } @article{rao_robustness_2011, title = {Robustness in biological systems}, url = {http://guava.physics.uiuc.edu/~nigel/courses/569/Essays_Fall2011/Files/deviprasad_rao.pdf}, urldate = {2015-11-26}, author = {Rao, Vikyath Deviprasad}, year = {2011}, keywords = {Robustness}, file = {Rao (2011) - Robustness in biological systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G8CNEPDS\\Rao (2011) - Robustness in biological systems.pdf:application/pdf} } @article{ebert_roles_2012, title = {Roles for {MicroRNAs} in {Conferring} {Robustness} to {Biological} {Processes}}, volume = {149}, issn = {0092-8674}, url = {http://www.sciencedirect.com/science/article/pii/S0092867412004643}, doi = {10.1016/j.cell.2012.04.005}, abstract = {Biological systems use a variety of mechanisms to maintain their functions in the face of environmental and genetic perturbations. Increasing evidence suggests that, among their roles as posttranscriptional repressors of gene expression, microRNAs (miRNAs) help to confer robustness to biological processes by reinforcing transcriptional programs and attenuating aberrant transcripts, and they may in some network contexts help suppress random fluctuations in transcript copy number. These activities have important consequences for normal development and physiology, disease, and evolution. Here, we will discuss examples and principles of miRNAs that contribute to robustness in animal systems.}, number = {3}, urldate = {2015-11-26}, journal = {Cell}, author = {Ebert, Margaret S. and Sharp, Phillip A.}, month = apr, year = {2012}, keywords = {miRNA}, pages = {515--524}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XPKIJH9X\\S0092867412004643.html:text/html} } @article{stelling_robustness_2004, title = {Robustness of {Cellular} {Functions}}, volume = {118}, issn = {0092-8674}, url = {http://www.sciencedirect.com/science/article/pii/S0092867404008402}, doi = {10.1016/j.cell.2004.09.008}, abstract = {Robustness, the ability to maintain performance in the face of perturbations and uncertainty, is a long-recognized key property of living systems. Owing to intimate links to cellular complexity, however, its molecular and cellular basis has only recently begun to be understood. Theoretical approaches to complex engineered systems can provide guidelines for investigating cellular robustness because biology and engineering employ a common set of basic mechanisms in different combinations. Robustness may be a key to understanding cellular complexity, elucidating design principles, and fostering closer interactions between experimentation and theory.}, number = {6}, urldate = {2015-11-30}, journal = {Cell}, author = {Stelling, Jörg and Sauer, Uwe and Szallasi, Zoltan and Doyle III, Francis J. and Doyle, John}, month = sep, year = {2004}, keywords = {Robustness}, pages = {675--685}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EEZAIAFM\\S0092867404008402.html:text/html;Stelling et al (2004) - Robustness of Cellular Functions.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V6F3TV39\\Stelling et al (2004) - Robustness of Cellular Functions.pdf:application/pdf} } @incollection{krakauer_robustness_2006, series = {Topics in {Biomedical} {Engineering} {International} {Book} {Series}}, title = {Robustness in {Biological} {Systems}: {A} {Provisional} {Taxonomy}}, copyright = {©2006 Springer Inc.}, isbn = {978-0-387-30241-6 978-0-387-33532-2}, shorttitle = {Robustness in {Biological} {Systems}}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/chapter/10.1007/978-0-387-33532-2_6}, abstract = {Biology is a domain of tension: on the one hand, biology is concerned with transformation and the generation of diversity; on the other, biology is concerned with the persistence of improbable structural regularities. The historical sciences in biology, principally evolution, have focused on change. The mechanistic sciences in biology, principally medicine, have focused on stability. Robustness, as a research program, aims to uncover those evolved mechanisms promoting the persistence of regularities. Here I organize mechanisms of robustness into a phenomenological taxonomy, grouping biological mechanisms into principles of robust organization. These include: Redundancy, Purging, Feedback, Modularity, Spatial Compartmentalization, Distributed Processing, and the Extended Phenotype. I present case studies in which mechanisms representative of each principle are described. These case studies serve to illustrate the ubiquity of specialized robustness mechanisms in all complex biosystems.}, language = {en}, urldate = {2015-11-26}, booktitle = {Complex {Systems} {Science} in {Biomedicine}}, publisher = {Springer US}, author = {Krakauer, David C.}, editor = {M.D, Thomas S. Deisboeck and F.A.C.C, J. Yasha Kresh}, year = {2006}, note = {DOI: 10.1007/978-0-387-33532-2\_6}, keywords = {Biomedical Engineering, Biomedicine general, Developmental biology, Neurosciences, Robustness}, pages = {183--205}, file = {Krakauer (2006) - Robustness in Biological Systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XTN73Z66\\Krakauer (2006) - Robustness in Biological Systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S6DZNDKE\\978-0-387-33532-2_6.html:text/html} } @article{kitano_towards_2007, title = {Towards a theory of biological robustness}, volume = {3}, issn = {1744-4292}, url = {http://msb.embopress.org/cgi/doi/10.1038/msb4100179}, doi = {10.1038/msb4100179}, urldate = {2015-12-01}, journal = {Molecular Systems Biology}, author = {Kitano, Hiroaki}, month = sep, year = {2007}, keywords = {Robustness} } @incollection{vera_microrna-regulated_2013, series = {Advances in {Experimental} {Medicine} and {Biology}}, title = {{MicroRNA}-{Regulated} {Networks}: {The} {Perfect} {Storm} for {Classical} {Molecular} {Biology}, the {Ideal} {Scenario} for {Systems} {Biology}}, copyright = {©2013 Springer Science+Business Media Dordrecht}, isbn = {978-94-007-5589-5 978-94-007-5590-1}, shorttitle = {{MicroRNA}-{Regulated} {Networks}}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/chapter/10.1007/978-94-007-5590-1_4}, abstract = {MicroRNAs (miRNAs) are involved in many regulatory pathways some of which are complex networks enriched in regulatory motifs like positive or negative feedback loops or coherent and incoherent feedforward loops. Their complexity makes the understanding of their regulation difficult and the interpretation of experimental data cumbersome. In this book chapter we claim that systems biology is the appropriate approach to investigate the regulation of these miRNA-regulated networks. Systems biology is an interdisciplinary approach by which biomedical questions on biochemical networks are addressed by integrating experiments with mathematical modelling and simulation. We here introduce the foundations of the systems biology approach, the basic theoretical and computational tools used to perform model-based analyses of miRNA-regulated networks and review the scientific literature in systems biology of miRNA regulation, with a focus on cancer.}, language = {en}, number = {774}, urldate = {2015-12-01}, booktitle = {{MicroRNA} {Cancer} {Regulation}}, publisher = {Springer Netherlands}, author = {Vera, Julio and Lai, Xin and Schmitz, Ulf and Wolkenhauer, Olaf}, editor = {Schmitz, Ulf and Wolkenhauer, Olaf and Vera, Julio}, year = {2013}, note = {DOI: 10.1007/978-94-007-5590-1\_4}, keywords = {bioinformatics, Bistability, Cancer Research, Computational Biology/Bioinformatics, Feedback loop, Feedforward loop, Gene expression, Kinetic models, miRNA, miRNA cluster, miRNA network motifs, miRNA regulated networks, miRNA target hub, Molecular Medicine, Post-transcriptional regulation, Systems Biology, Ultrasensitivity}, pages = {55--76}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8WRSVDKX\\978-94-007-5590-1_4.html:text/html;Vera et al (2013) - MicroRNA-Regulated Networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CIVPM9AV\\Vera et al (2013) - MicroRNA-Regulated Networks.pdf:application/pdf} } @book{borutzky_bond_2010, title = {Bond {Graph} {Methodology}}, publisher = {Springer}, author = {Borutzky, Wolfgang}, year = {2010}, keywords = {Bond graphs}, file = {Borutzky (2010) - Bond Graph Methodology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\68JIW3AZ\\Borutzky (2010) - Bond Graph Methodology.pdf:application/pdf} } @article{lu_tristability_2013, title = {Tristability in {Cancer}-{Associated} {MicroRNA}-{TF} {Chimera} {Toggle} {Switch}}, volume = {117}, issn = {1520-6106}, url = {http://dx.doi.org/10.1021/jp403156m}, doi = {10.1021/jp403156m}, abstract = {Cell fate decisions during embryonic development and tumorigenesis pose a major research challenge in modern developmental and cancer biology. Binary cell fate decisions are usually regulated by gene circuits incorporating either classical toggle switches with two mutually inhibiting transcription factor (TF) genes or chimera toggle switches with a mutually inhibiting pair of microRNA (miRNA) and TF gene. These circuits can explain binary cell fate decisions. Importantly, intermediate cell types can exist during the differentiation of both stem cells and cancer cells. It has been shown that TF-TF self-activating toggle switches (SATS) can have coexistence of three metastable states (tristability), yet the role of chimera toggle switches in opening these additional states remains elusive. Here we present a generalized framework for both the TF-TF SATS and miRNA-TF chimera SATS, starting from the TF-promoter and miRNA-mRNA binding/unbinding dynamics. We show that the chimera SATSs can also have tristability. We demonstrate that the dynamics of miRNA-TF SATS is qualitatively different from that of the TF-TF SATS because the nonlinear effects of translational silencing by miRNA are distinct from those of transcriptional repression. We discuss the possible relevance of these findings to fate decisions by cancer cells.}, number = {42}, urldate = {2015-12-02}, journal = {The Journal of Physical Chemistry B}, author = {Lu, Mingyang and Jolly, Mohit Kumar and Gomoto, Ryan and Huang, Bin and Onuchic, José and Ben-Jacob, Eshel}, month = oct, year = {2013}, pages = {13164--13174}, file = {ACS Full Text Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TEPQAJS3\\jp403156m.html:text/html;Lu et al (2013) - Tristability in Cancer-Associated MicroRNA-TF Chimera Toggle Switch.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\94EIA4GP\\Lu et al (2013) - Tristability in Cancer-Associated MicroRNA-TF Chimera Toggle Switch.pdf:application/pdf} } @article{hofmeyr_reversible_1997, title = {The reversible {Hill} equation: how to incorporate cooperative enzymes into metabolic models}, volume = {13}, issn = {1367-4803, 1460-2059}, shorttitle = {The reversible {Hill} equation}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/13/4/377}, doi = {10.1093/bioinformatics/13.4.377}, abstract = {Motivation: Realistic simulation of the kinetic properties of metabolic pathways requires rate equations to be expressed in reversible form, because substrate and product elasticities are drastically different in reversible and irreversible reactions. This presents no special problem for reactions that follow reversible Michaelis-Menten kinetics, but for enzymes showing cooperative kinetics the full reversible rate equations are extremely complicated, and anyway in virtually all cases the full equations are unknown because suflciently complete kinetic studies have not been carried out. There is a need, therefore, for approximate reversible equations that allow convenient simulation without violating thermodynamic constraints. Results: We show how the irreversible Hill equation can be generalized to a reversible form, including effects of modijiers. The proposed equation leads to behaviour virtually indistinguishable from that predicted by a kinetic form of the Adair equation, despite the fact that the latter is a far more complicated equation. By contrast, a reversible form of the Monod-Wyman-Changeux equation that has sometimes been used leads to predictions for the effects of modifiers at high substrate concentration that differ qualitatively from those given by the Adair equation. Contact: Email: jhsh@maties.sun.ac.za; athel@ibsm.cnrsmrs.fr}, language = {en}, number = {4}, urldate = {2015-12-03}, journal = {Computer applications in the biosciences : CABIOS}, author = {Hofmeyr, Jan-Hendrik S. and Cornish-Bowden, Hofmeyr}, month = aug, year = {1997}, pmid = {9283752}, keywords = {Physical biochemistry}, pages = {377--385}, file = {Hofmeyr_Cornish-Bowden (1997) - The reversible Hill equation.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CK6PQDM2\\Hofmeyr_Cornish-Bowden (1997) - The reversible Hill equation.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NW222KBZ\\377.html:text/html} } @article{wang_toward_2010, title = {Toward a system-level understanding of {microRNA} pathway via mathematical modeling}, volume = {100}, issn = {0303-2647}, url = {http://www.sciencedirect.com/science/article/pii/S030326470900207X}, doi = {10.1016/j.biosystems.2009.12.005}, abstract = {The microRNA (miRNA) pathway plays multiple roles in regulating mechanisms controlling both physiological and pathological processes such as the cell proliferation and cancers. But little is known about the dynamic properties, key rate-limiting steps as well as the stochastic noise in this pathway. Presently, a system-theoretic approach was presented to analyze and quantitative modeling of a generic miRNA pathway, which can be implemented deterministically and stochastically. Our results show that the inferred dynamic properties obtained from the mathematical models of the miRNA pathway are well consistent with previous experimental observations. By sensitivity analysis, the key steps in this pathway were found to be the miRNA gene transcription, RISC decay and mRNA formation. In addition, the results of quantified noise strength along the pathway demonstrate that the pathway can reduce the ingress noise and reveal the noise robustness property. Our findings also present testable hypothesis for experimental biologists to further investigate miRNA's increasing functional roles in regulating various cellular processes.}, number = {1}, urldate = {2015-12-03}, journal = {Biosystems}, author = {Wang, Xia and Li, Yan and Xu, Xue and Wang, Yong-hua}, month = apr, year = {2010}, keywords = {Deterministic models, MicroRNA pathway, miRNA, Noise, Sensitivity analysis, Stochastic models}, pages = {31--38}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZCETVP3P\\S030326470900207X.html:text/html} } @article{mavrovouniotis_estimation_1991, title = {Estimation of standard {Gibbs} energy changes of biotransformations.}, volume = {266}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/266/22/14440}, abstract = {Contributions and corrections for the estimation of standard Gibbs energies are given. The group contribution method, applicable to both cyclic and acyclic compounds, permits the approximate estimation of the standard Gibbs energy of a biotransformation, given the stoichiometry and structures of the metabolites involved. Estimated standard Gibbs energies of formation for a number of acyclic biochemical compounds are provided.}, language = {en}, number = {22}, urldate = {2015-12-06}, journal = {Journal of Biological Chemistry}, author = {Mavrovouniotis, M. L.}, month = aug, year = {1991}, pmid = {1860851}, keywords = {Physical biochemistry}, pages = {14440--14445}, file = {Mavrovouniotis (1991) - Estimation of standard Gibbs energy changes of biotransformations.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VUICKS7V\\Mavrovouniotis (1991) - Estimation of standard Gibbs energy changes of biotransformations.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IQJNB374\\14440.html:text/html} } @article{crampin_computational_2004, title = {Computational physiology and the physiome project}, volume = {89}, issn = {1469-445X}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/expphysiol.2003.026740/abstract}, doi = {10.1113/expphysiol.2003.026740}, abstract = {Bioengineering analyses of physiological systems use the computational solution of physical conservation laws on anatomically detailed geometric models to understand the physiological function of intact organs in terms of the properties and behaviour of the cells and tissues within the organ. By linking behaviour in a quantitative, mathematically defined sense across multiple scales of biological organization – from proteins to cells, tissues, organs and organ systems – these methods have the potential to link patient-specific knowledge at the two ends of these spatial scales. A genetic profile linked to cardiac ion channel mutations, for example, can be interpreted in relation to body surface ECG measurements via a mathematical model of the heart and torso, which includes the spatial distribution of cardiac ion channels throughout the myocardium and the individual kinetics for each of the approximately 50 types of ion channel, exchanger or pump known to be present in the heart. Similarly, linking molecular defects such as mutations of chloride ion channels in lung epithelial cells to the integrated function of the intact lung requires models that include the detailed anatomy of the lungs, the physics of air flow, blood flow and gas exchange, together with the large deformation mechanics of breathing. Organizing this large body of knowledge into a coherent framework for modelling requires the development of ontologies, markup languages for encoding models, and web-accessible distributed databases. In this article we review the state of the field at all the relevant levels, and the tools that are being developed to tackle such complexity. Integrative physiology is central to the interpretation of genomic and proteomic data, and is becoming a highly quantitative, computer-intensive discipline.}, language = {en}, number = {1}, urldate = {2015-12-06}, journal = {Experimental Physiology}, author = {Crampin, Edmund J. and Halstead, Matthew and Hunter, Peter and Nielsen, Poul and Noble, Denis and Smith, Nicolas and Tawhai, Merryn}, month = jan, year = {2004}, pages = {1--26}, file = {Crampin et al (2004) - Computational physiology and the physiome project.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XHM9EBFP\\Crampin et al (2004) - Computational physiology and the physiome project.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DMHG2VEP\\abstract.html:text/html} } @article{roberts_computational_2012, title = {Computational approaches to understand cardiac electrophysiology and arrhythmias}, volume = {303}, copyright = {Copyright © 2012 the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/303/7/H766}, doi = {10.1152/ajpheart.01081.2011}, abstract = {Cardiac rhythms arise from electrical activity generated by precisely timed opening and closing of ion channels in individual cardiac myocytes. These impulses spread throughout the cardiac muscle to manifest as electrical waves in the whole heart. Regularity of electrical waves is critically important since they signal the heart muscle to contract, driving the primary function of the heart to act as a pump and deliver blood to the brain and vital organs. When electrical activity goes awry during a cardiac arrhythmia, the pump does not function, the brain does not receive oxygenated blood, and death ensues. For more than 50 years, mathematically based models of cardiac electrical activity have been used to improve understanding of basic mechanisms of normal and abnormal cardiac electrical function. Computer-based modeling approaches to understand cardiac activity are uniquely helpful because they allow for distillation of complex emergent behaviors into the key contributing components underlying them. Here we review the latest advances and novel concepts in the field as they relate to understanding the complex interplay between electrical, mechanical, structural, and genetic mechanisms during arrhythmia development at the level of ion channels, cells, and tissues. We also discuss the latest computational approaches to guiding arrhythmia therapy.}, language = {en}, number = {7}, urldate = {2015-12-07}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Roberts, Byron N. and Yang, Pei-Chi and Behrens, Steven B. and Moreno, Jonathan D. and Clancy, Colleen E.}, month = oct, year = {2012}, pmid = {22886409}, keywords = {SERCA}, pages = {H766--H783}, file = {Roberts et al (2012) - Computational approaches to understand cardiac electrophysiology and arrhythmias.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4X6FTDTZ\\Roberts et al (2012) - Computational approaches to understand cardiac electrophysiology and arrhythmias.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U6UTPPFI\\H766.html:text/html} } @article{jolly_implications_2015, title = {Implications of the hybrid epithelial/mesenchymal phenotype in metastasis}, url = {http://journal.frontiersin.org/article/10.3389/fonc.2015.00155/full}, doi = {10.3389/fonc.2015.00155}, abstract = {Transitions between epithelial and mesenchymal phenotypes – the epithelial to ­mesenchymal transition (EMT) and its reverse the mesenchymal to epithelial transition (MET) – are hallmarks of cancer metastasis. While transitioning between the epithelial and mesenchymal phenotypes, cells can also attain a hybrid epithelial/mesenchymal (E/M) (i.e., partial or intermediate EMT) phenotype. Cells in this phenotype have mixed epithelial (e.g., adhesion) and mesenchymal (e.g., migration) properties, thereby allowing them to move collectively as clusters. If these clusters reach the bloodstream intact, they can give rise to clusters of circulating tumor cells (CTCs), as have often been seen experimentally. Here, we review the operating principles of the core regulatory network for EMT/MET that acts as a “three-way” switch giving rise to three distinct phenotypes – E, M and hybrid E/M – and present a theoretical framework that can elucidate the role of many other players in regulating epithelial plasticity. Furthermore, we highlight recent studies on partial EMT and its association with drug resistance and tumor-initiating potential; and discuss how cell–cell communication between cells in a partial EMT phenotype can enable the formation of clusters of CTCs. These clusters can be more apoptosis-resistant and have more tumor-initiating potential than singly moving CTCs with a wholly mesenchymal (complete EMT) phenotype. Also, more such clusters can be formed under inflammatory conditions that are often generated by various therapies. Finally, we discuss the multiple advantages that the partial EMT or hybrid E/M phenotype have as compared to a complete EMT phenotype and argue that these collectively migrating cells are the primary “bad actors” of metastasis.}, urldate = {2015-12-07}, journal = {Stem Cell Research}, author = {Jolly, Mohit Kumar and Boareto, Marcelo and Huang, Bin and Jia, Dongya and Lu, Mingyang and Ben-Jacob, Eshel and Onuchic, José N. and Levine, Herbert}, year = {2015}, keywords = {cancer stem cells, cancer systems biology, cell-fate decisions, intermediate EMT, partial EMT}, pages = {155}, file = {Jolly et al (2015) - Implications of the hybrid epithelial-mesenchymal phenotype in metastasis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8GQWCIV7\\Jolly et al (2015) - Implications of the hybrid epithelial-mesenchymal phenotype in metastasis.pdf:application/pdf} } @article{zhou_mechanisms_2012, title = {Mechanisms generating bistability and oscillations in {microRNA}-mediated motifs}, volume = {85}, url = {http://link.aps.org/doi/10.1103/PhysRevE.85.041916}, doi = {10.1103/PhysRevE.85.041916}, abstract = {The importance of post-transcriptional regulation by microRNAs (miRNAs) has recently been recognized in almost all cellular processes. When participating in cellular processes, miRNAs mainly mediate mRNA degradation or translational repression. Recently computational and experimental studies have identified an abundance of motifs involving miRNAs and transcriptional factors (TFs). The simplest motif is a two-node miRNA-mediated feedback loop (MFL) in which a TF regulates an miRNA and the TF itself is negatively regulated by the miRNA. In this paper we present a general computational model for the MFL based on biochemical regulations and explore its dynamics by using bifurcation analysis. Our results show that the MFL can behave either as switches or as oscillators, depending on the TF as a repressor or an activator. These functional features are consistent with the widespread appearance of miRNAs in fate decisions such as proliferation, differentiation, and apoptosis during development. We found that under the interplay of a TF and an miRNA, the MFL model can behave as switches for wide ranges of parameters even without cooperative binding of the TF. In addition, oscillations induced by the miRNA in the MFL model require neither an additional positive feedback loop, nor self-activation of the gene, nor cooperative binding of the TF, nor saturated degradation. Therefore, the MFL may provide a general network structure to induce bistability or oscillations. It is hoped that the results presented here will provide a new view on how gene expression is regulated by miRNAs and further guidance for experiments. Moreover, the insight gained from this study is also expected to provide a basis for the investigation of more complex networks assembled by simple building blocks.}, number = {4}, urldate = {2015-12-07}, journal = {Physical Review E}, author = {Zhou, Peipei and Cai, Shuiming and Liu, Zengrong and Wang, Ruiqi}, month = apr, year = {2012}, keywords = {miRNA}, pages = {041916}, file = {APS Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IZ3EKQSR\\PhysRevE.85.html:text/html} } @article{berndt_high_2013, title = {The {High} {Energy} {Demand} of {Neuronal} {Cells} {Caused} by {Passive} {Leak} {Currents} is {Not} a {Waste} of {Energy}}, volume = {67}, issn = {1085-9195, 1559-0283}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s12013-013-9538-3}, doi = {10.1007/s12013-013-9538-3}, abstract = {It is estimated that maintenance of the resting potential of neurons consumes between 15 \% (in gray matter) and 44 \% (in fully myelinated white matter) of the brain’s total energy budget [1]. This poses the intriguing question why evolution has not strived to lower the permeability of passive ion channels to cut the high resting-state energy budget of the brain. Based on a conceptual mathematical model of neuronal ion currents and action potential (AP) firing we demonstrate that a neuron endowed with small leak currents and correspondingly low energy consumption by the Na+/K+-ATPase in the resting state may indeed recapitulate all features of normal AP firing. However, the activation and inactivation of such a “low-energy-cost neuron” turns out to be extremely sensitive to small fluctuation of Na+ currents associated with Na+-dependent secondary-active transport that is indispensable for the metabolic integrity of the cell and neurotransmitter recycling. We provide evidence that sufficiently large leak currents function as important stabilizers of the membrane potential and thus are required to allow robust AP firing. Our simulations suggest that the energy demand of the Na+/K+-ATPase needed to counterbalance passive leak currents cannot be significantly dropped below observed values.}, language = {en}, number = {2}, urldate = {2015-12-08}, journal = {Cell Biochemistry and Biophysics}, author = {Berndt, Nikolaus and Holzhütter, Hermann-Georg}, month = mar, year = {2013}, keywords = {Biochemistry, general, Biophysics and Biological Physics, Biotechnology, Cell Biology, Information processing fidelity, Leak channels, Neuron, Neuronal energy efficiency, Pharmacology/Toxicology, Robustness}, pages = {527--535}, file = {Berndt_Holzhütter (2013) - The High Energy Demand of Neuronal Cells Caused by Passive Leak Currents is Not.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XGHMX6S6\\Berndt_Holzhütter (2013) - The High Energy Demand of Neuronal Cells Caused by Passive Leak Currents is Not.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MSKGVW8V\\s12013-013-9538-3.html:text/html} } @article{heinrich_metabolic_1978, title = {Metabolic regulation and mathematical models}, volume = {32}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/0079610778900172}, doi = {10.1016/0079-6107(78)90017-2}, urldate = {2015-12-07}, journal = {Progress in Biophysics and Molecular Biology}, author = {Heinrich, R. and Rapoport, S. M. and Rapoport, T. A.}, month = jan, year = {1978}, keywords = {Metabolism, Physical biochemistry}, pages = {1--82}, file = {Heinrich et al (1978) - Metabolic regulation and mathematical models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\86V8M2AA\\Heinrich et al (1978) - Metabolic regulation and mathematical models.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NKZZ26XW\\0079610778900172.html:text/html} } @article{cloutier_control_2009, title = {The control systems structures of energy metabolism}, copyright = {© 2009 The Royal Society}, issn = {1742-5689, 1742-5662}, url = {http://rsif.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/early/2009/10/13/rsif.2009.0371}, doi = {10.1098/rsif.2009.0371}, abstract = {The biochemical regulation of energy metabolism (EM) allows cells to modulate their energetic output depending on available substrates and requirements. To this end, numerous biomolecular mechanisms exist that allow the sensing of the energetic state and corresponding adjustment of enzymatic reaction rates. This regulation is known to induce dynamic systems properties such as oscillations or perfect adaptation. Although the various mechanisms of energy regulation have been studied in detail from many angles at the experimental and theoretical levels, no framework is available for the systematic analysis of EM from a control systems perspective. In this study, we have used principles well known in control to clarify the basic system features that govern EM. The major result is a subdivision of the biomolecular mechanisms of energy regulation in terms of widely used engineering control mechanisms: proportional, integral, derivative control, and structures: feedback, cascade and feed-forward control. Evidence for each mechanism and structure is demonstrated and the implications for systems properties are shown through simulations. As the equivalence between biological systems and control components presented here is generic, it is also hypothesized that our work could eventually have an applicability that is much wider than the focus of the current study.}, language = {en}, urldate = {2015-12-07}, journal = {Journal of The Royal Society Interface}, author = {Cloutier, Mathieu and Wellstead, Peter}, month = oct, year = {2009}, pmid = {19828503}, keywords = {Metabolism}, pages = {rsif20090371}, file = {Cloutier_Wellstead (2009) - The control systems structures of energy metabolism.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CJP6GZH7\\Cloutier_Wellstead (2009) - The control systems structures of energy metabolism.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PIN9J786\\rsif.2009.0371.html:text/html} } @article{jensen_endothelin-converting_2014, title = {Endothelin-converting {Enzyme} 1 and β-{Arrestins} {Exert} {Spatiotemporal} {Control} of {Substance} {P}-induced {Inflammatory} {Signals}}, volume = {289}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/289/29/20283}, doi = {10.1074/jbc.M114.578179}, abstract = {Although the intracellular trafficking of G protein-coupled receptors controls specific signaling events, it is unclear how the spatiotemporal control of signaling contributes to complex pathophysiological processes such as inflammation. By using bioluminescence resonance energy transfer and superresolution microscopy, we found that substance P (SP) induces the association of the neurokinin 1 receptor (NK1R) with two classes of proteins that regulate SP signaling from plasma and endosomal membranes: the scaffolding proteins β-arrestin (βARRs) 1 and 2 and the transmembrane metallopeptidases ECE-1c and ECE-1d. In HEK293 cells and non-transformed human colonocytes, we observed that G protein-coupled receptor kinase 2 and βARR1/2 terminate plasma membrane Ca2+ signaling and initiate receptor trafficking to endosomes that is necessary for sustained activation of ERKs in the nucleus. βARRs deliver the SP-NK1R endosomes, where ECE-1 associates with the complex, degrades SP, and allows the NK1R, freed from βARRs, to recycle. Thus, both ECE-1 and βARRs mediate the resensitization of NK1R Ca2+ signaling at the plasma membrane. Sustained exposure of colonocytes to SP activates NF-κB and stimulates IL-8 secretion. This proinflammatory signaling is unaffected by inhibition of the endosomal ERK pathway but is suppressed by ECE-1 inhibition or βARR2 knockdown. Inhibition of protein phosphatase 2A, which also contributes to sustained NK1R signaling at the plasma membrane, similarly attenuates IL-8 secretion. Thus, the primary function of βARRs and ECE-1 in SP-dependent inflammatory signaling is to promote resensitization, which allows the sustained NK1R signaling from the plasma membrane that drives inflammation.}, language = {en}, number = {29}, urldate = {2015-12-10}, journal = {Journal of Biological Chemistry}, author = {Jensen, Dane D. and Halls, Michelle L. and Murphy, Jane E. and Canals, Meritxell and Cattaruzza, Fiore and Poole, Daniel P. and Lieu, TinaMarie and Koon, Hon-Wai and Pothoulakis, Charalabos and Bunnett, Nigel W.}, month = jul, year = {2014}, pmid = {24898255}, keywords = {Arrestins, Cell Signaling, G Protein-coupled Receptor (GPCR), Inflammation, Intracellular Trafficking, Neuropeptide, Pain circuits, Receptor Endocytosis}, pages = {20283--20294}, file = {Jensen et al (2014) - Endothelin-converting Enzyme 1 and β-Arrestins Exert Spatiotemporal Control of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MK4ZJIWU\\Jensen et al (2014) - Endothelin-converting Enzyme 1 and β-Arrestins Exert Spatiotemporal Control of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TI482JPC\\20283.html:text/html} } @article{tran_metabolite-sensitive_2010, title = {A {Metabolite}-{Sensitive}, {Thermodynamically} {Constrained} {Model} of {Cardiac} {Cross}-{Bridge} {Cycling}: {Implications} for {Force} {Development} during {Ischemia}}, volume = {98}, issn = {0006-3495}, shorttitle = {A {Metabolite}-{Sensitive}, {Thermodynamically} {Constrained} {Model} of {Cardiac} {Cross}-{Bridge} {Cycling}}, url = {http://www.sciencedirect.com/science/article/pii/S0006349509016178}, doi = {10.1016/j.bpj.2009.10.011}, abstract = {We present a metabolically regulated model of cardiac active force generation with which we investigate the effects of ischemia on maximum force production. Our model, based on a model of cross-bridge kinetics that was developed by others, reproduces many of the observed effects of MgATP, MgADP, Pi, and H+ on force development while retaining the force/length/Ca2+ properties of the original model. We introduce three new parameters to account for the competitive binding of H+ to the Ca2+ binding site on troponin C and the binding of MgADP within the cross-bridge cycle. These parameters, along with the Pi and H+ regulatory steps within the cross-bridge cycle, were constrained using data from the literature and validated using a range of metabolic and sinusoidal length perturbation protocols. The placement of the MgADP binding step between two strongly-bound and force-generating states leads to the emergence of an unexpected effect on the force-MgADP curve, where the trend of the relationship (positive or negative) depends on the concentrations of the other metabolites and [H+]. The model is used to investigate the sensitivity of maximum force production to changes in metabolite concentrations during the development of ischemia.}, number = {2}, urldate = {2015-12-15}, journal = {Biophysical Journal}, author = {Tran, Kenneth and Smith, Nicolas P. and Loiselle, Denis S. and Crampin, Edmund J.}, month = jan, year = {2010}, keywords = {Actin-myosin}, pages = {267--276}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QEU3IEIP\\S0006349509016178.html:text/html;Tran et al (2010) - A Metabolite-Sensitive, Thermodynamically Constrained Model of Cardiac.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HSIWZKFW\\Tran et al (2010) - A Metabolite-Sensitive, Thermodynamically Constrained Model of Cardiac.pdf:application/pdf} } @article{gawthrop_energetic_2015, title = {The {Energetic} {Cost} of the {Action} {Potential}: {Bond} {Graph} {Modelling} of {Electrochemical} {Energy} {Transduction} in {Excitable} {Membranes}}, shorttitle = {The {Energetic} {Cost} of the {Action} {Potential}}, url = {http://arxiv.org/abs/1512.00956}, abstract = {The energy consumed during an action potential event must be replaced, ultimately by the metabolic system of the organism. As discussed by a number of authors, there is a trade-off between the speed of an action potential event and energy consumption and, moreover, this consumption can be optimised by adjusting ion channel density and gating time constants. The energy consumption is dependent on both species and type of neuron. The influx of Na is often taken as a proxy for energy consumption. For example, 3Na ions can be expelled using one ATP molecule within the sodium-potassium pump. Thus 1/3 of the Na can be taken as a proxy for energy consumption. In contrast, this paper presents an energy based model of action potentials and thus can be directly used to compute energy consumption in both healthy and diseased neurons. These results are illustrated by comparing the energy consumption of healthy and degenerative retinal ganglion cells using both simulated and in vitro data.}, urldate = {2015-12-17}, journal = {arXiv:1512.00956 [physics, q-bio]}, author = {Gawthrop, Peter J. and Siekmann, Ivo and Kameneva, Tatiana and Saha, Susmita and Ibbotson, Michael R. and Crampin, Edmund J.}, month = dec, year = {2015}, note = {arXiv: 1512.00956}, keywords = {Bond graphs, Physics - Biological Physics, Quantitative Biology - Quantitative Methods}, file = {arXiv.org Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RQWJTZZT\\1512.html:text/html;Gawthrop et al (2015) - The Energetic Cost of the Action Potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BFU6KC7R\\Gawthrop et al (2015) - The Energetic Cost of the Action Potential.pdf:application/pdf} } @article{kemp_amp-activated_2003, title = {{AMP}-activated protein kinase, super metabolic regulator}, volume = {31}, copyright = {Copyright 2003 Biochemical Society}, issn = {0300-5127, 1470-8752}, url = {http://www.biochemsoctrans.org/content/31/1/162}, doi = {10.1042/bst0310162}, abstract = {The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression.}, language = {en}, number = {1}, urldate = {2015-12-18}, journal = {Biochemical Society Transactions}, author = {Kemp, B. E. and Stapleton, D. and Campbell, D. J. and Chen, Z.-P. and Murthy, S. and Walter, M. and Gupta, A. and Adams, J. J. and Katsis, F. and Denderen, B. van and Jennings, I. G. and Iseli, T. and Michell, B. J. and Witters, L. A.}, month = feb, year = {2003}, pmid = {12546677}, keywords = {AMPK}, pages = {162--168}, file = {Kemp et al (2003) - AMP-activated protein kinase, super metabolic regulator.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8RVT84XK\\Kemp et al (2003) - AMP-activated protein kinase, super metabolic regulator.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KMGBX2J3\\162.html:text/html} } @article{hardie_amp-activated_1997, title = {The {AMP}-{Activated} {Protein} {Kinase}}, volume = {246}, issn = {1432-1033}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/j.1432-1033.1997.00259.x/abstract}, doi = {10.1111/j.1432-1033.1997.00259.x}, abstract = {A single entity, the AMP-activated protein kinase (AMPK), phosphorylates and regulates in vivo hydroxymethylglutraryl-CoA reductase and acetyl-CoA carboxylase (key regulatory enzymes of sterol synthesis and fatty acid synthesis, respectively), and probably many additional targets. The kinase is activated by high AMP and low ATP via a complex mechanism, which involves allosteric regulation, promotion of phosphorylation by an upstream protein kinase (AMPK kinase), and inhibition of dephosphorylation. This protein-kinase cascade represents a sensitive system, which is activated by cellular stresses that deplete ATP, and thus acts like a cellular fuel gauge. Our central hypothesis is that, when it detects a ‘low-fuel’ situation, it protects the cell by switching off ATP-consuming pathways (e.g. fatty acid synthesis and sterol synthesis) and switching on alternative pathways for ATP generation (e.g. fatty acid oxidation). Native AMP-activated protein kinase is a heterotrimer consisting of a catalytic α subunit, and β and γ subunits, which are also essential for activity. All three subunits have homologues in budding yeast, which are components of the SNF1 protein-kinase complex. SNF1 is activated by glucose starvation (which in yeast leads to ATP depletion) and genetic studies have shown that it is involved in derepression of glucose-repressed genes. This raises the intriguing possibility that AMPK may regulate gene expression in mammals. AMPK/SNF1 homologues are found in higher plants, and this protein-kinase cascade appears to be an ancient system which evolved to protect cells against the effects of nutritional or environmental stress.}, language = {en}, number = {2}, urldate = {2015-12-18}, journal = {European Journal of Biochemistry}, author = {Hardie, D. Grahame and Carling, David}, month = jun, year = {1997}, keywords = {acetyl-CoA carboxylase, AMP-activated protein kinase, AMPK, ATP levels, environmental stress, fuel gauge, hydroxymethyl-glutaryl-CoA reductase, kinase cascade, phosphorylation, SNF1}, pages = {259--273}, file = {Hardie_Carling (1997) - The AMP-Activated Protein Kinase.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V8V82MSE\\Hardie_Carling (1997) - The AMP-Activated Protein Kinase.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GEH6NMFB\\abstract.html:text/html} } @article{hardie_amp-activated_2011, title = {{AMP}-activated protein kinase—an energy sensor that regulates all aspects of cell function}, volume = {25}, issn = {0890-9369, 1549-5477}, url = {http://genesdev.cshlp.org/content/25/18/1895}, doi = {10.1101/gad.17420111}, abstract = {AMP-activated protein kinase (AMPK) is a sensor of energy status that maintains cellular energy homeostasis. It arose very early during eukaryotic evolution, and its ancestral role may have been in the response to starvation. Recent work shows that the kinase is activated by increases not only in AMP, but also in ADP. Although best known for its effects on metabolism, AMPK has many other functions, including regulation of mitochondrial biogenesis and disposal, autophagy, cell polarity, and cell growth and proliferation. Both tumor cells and viruses establish mechanisms to down-regulate AMPK, allowing them to escape its restraining influences on growth.}, language = {en}, number = {18}, urldate = {2015-12-18}, journal = {Genes \& Development}, author = {Hardie, D. Grahame}, month = sep, year = {2011}, pmid = {21937710}, keywords = {AMP-activated protein kinase, AMPK, AMPK, autophagy, cell polarity, cell proliferation, Metabolism}, pages = {1895--1908}, file = {Hardie (2011) - AMP-activated protein kinase—an energy sensor that regulates all aspects of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JQPF46CE\\Hardie (2011) - AMP-activated protein kinase—an energy sensor that regulates all aspects of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7RT8Z6RR\\1895.html:text/html} } @article{rosenfeld_influence_2014, title = {The influence of filament elasticity on transients after sudden alteration of length of muscle or load}, volume = {43}, issn = {0175-7571, 1432-1017}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s00249-014-0968-7}, doi = {10.1007/s00249-014-0968-7}, abstract = {The duration of phase 2 of a transient after sudden reduction of the length of a muscle or a load on it decreases rapidly with increasing amplitude of the jump. This is mainly due to the increasing role of the superfast relaxation processes with a characteristic time of about 0.1 ms. Mainly in order to explain this effect, Huxley and Simmons proposed their famous model of force generation in 1971. The present paper examines the effect of elasticity of filaments on relaxation processes. It is shown that if the filaments are not perfectly elastic, the superfast tension transient may result from a delay of redistribution of stresses within actin and/or myosin filaments at the beginning of phase 2. Corresponding redistribution of deformations within the actin filaments leads to non-uniform shifts of the attached myosin heads and changes in the X-ray diffraction pattern. Additionally, we discuss a change in the experimental technique that allows suppression of the elastic vibrations that obscure the contributions of other sources to the superfast tension transient.}, language = {en}, number = {8-9}, urldate = {2016-01-03}, journal = {European Biophysics Journal}, author = {Rosenfeld, E. V.}, month = jun, year = {2014}, keywords = {Actin-myosin, Biochemistry, general, Biophysics and Biological Physics, Cell Biology, Filament elasticity, Membrane Biology, Myosin head, Nanotechnology, Neurobiology, Tension transient}, pages = {367--376}, file = {Rosenfeld (2014) - The influence of filament elasticity on transients after sudden alteration of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\58VPRNEI\\Rosenfeld (2014) - The influence of filament elasticity on transients after sudden alteration of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\A42HQGCH\\s00249-014-0968-7.html:text/html} } @article{lan_mechanochemical_2012, title = {Mechanochemical models of processive molecular motors}, volume = {110}, issn = {0026-8976}, url = {http://dx.doi.org/10.1080/00268976.2012.677863}, doi = {10.1080/00268976.2012.677863}, abstract = {Motor proteins are the molecular engines powering the living cell. These nanometre-sized molecules convert chemical energy, both enthalpic and entropic, into useful mechanical work. High resolution single molecule experiments can now observe motor protein movement with increasing precision. The emerging data must be combined with structural and kinetic measurements to develop a quantitative mechanism. This article describes a modelling framework where quantitative understanding of motor behaviour can be developed based on the protein structure. The framework is applied to myosin motors, with emphasis on how synchrony between motor domains give rise to processive unidirectional movement. The modelling approach shows that the elasticity of protein domains are important in regulating motor function. Simple models of protein domain elasticity are presented. The framework can be generalized to other motor systems, or an ensemble of motors such as muscle contraction. Indeed, for hundreds of myosins, our framework can be reduced to the Huxely–Simmons description of muscle movement in the mean-field limit.}, number = {9-10}, urldate = {2016-01-03}, journal = {Molecular Physics}, author = {Lan, Ganhui and Sun, Sean X.}, month = may, year = {2012}, keywords = {molecular motors}, pages = {1017--1034}, file = {Lan_Sun (2012) - Mechanochemical models of processive molecular motors.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6NF5JCV6\\Lan_Sun (2012) - Mechanochemical models of processive molecular motors.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PJK5BFDE\\00268976.2012.html:text/html} } @article{bhattacharya-ghosh_multi-physics_2012, title = {A multi-physics and multi-scale lumped parameter model of cardiac contraction of the left ventricle: {A} conceptual model from the protein to the organ scale}, volume = {42}, issn = {0010-4825}, shorttitle = {A multi-physics and multi-scale lumped parameter model of cardiac contraction of the left ventricle}, url = {http://www.sciencedirect.com/science/article/pii/S0010482512001205}, doi = {10.1016/j.compbiomed.2012.07.010}, abstract = {In cardiovascular computational physiology the importance of understanding cardiac contraction as a multi-scale process is of paramount importance to understand causality across different scales. Within this study, a multi-scale and multi-physics model of the left ventricle that connects the process of cardiac excitation and contraction from the protein to the organ level is presented in a novel way. The model presented here includes the functional description of a cardiomyocyte (cellular scale), which explains the dynamic behaviour of the calcium concentration within the cell whilst an action potential develops. The cell domain is coupled to a domain that determines the kinetics of the sliding filament mechanism (protein level), which is at the basis of cardiac contraction. These processes are then linked to the generation of muscular force and from there to the generation of pressure inside the ventricle. This multi-scale model presents a coherent and unified way to describe cardiac contraction from the protein to the organ level.}, number = {10}, urldate = {2016-01-03}, journal = {Computers in Biology and Medicine}, author = {Bhattacharya-Ghosh, Benjamin and Schievano, Silvia and Díaz-Zuccarini, Vanessa}, month = oct, year = {2012}, keywords = {Calcium signalling, Cross-bridge kinetics, Dynamic calcium concentration, Excitation contraction coupling process, Left ventricular contraction, Multi-scale modelling and simulation, SERCA}, pages = {982--992}, file = {Bhattacharya-Ghosh et al (2012) - A multi-physics and multi-scale lumped parameter model of cardiac contraction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4RST2T59\\Bhattacharya-Ghosh et al (2012) - A multi-physics and multi-scale lumped parameter model of cardiac contraction.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\A6N8T7WG\\S0010482512001205.html:text/html} } @article{rosenfeld_interrelation_2012, title = {The interrelation between mechanical characteristics of contracting muscle, cross-bridge internal structure, and the mechanism of chemomechanical energy transduction}, volume = {41}, issn = {0175-7571, 1432-1017}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s00249-012-0849-x}, doi = {10.1007/s00249-012-0849-x}, abstract = {The cross-bridge working stroke is regarded as a continuous (without jumps) change of myosin head internal state under the action of a force exerted within the nucleotide-binding site. Involvement of a concept of continuous cross-bridge conformation enables discussion of the nature of the force propelling muscle, and the Coulomb repulsion of like-charged adenosine triphosphate (ATP) fragments ADP2− and P i 2− can quite naturally be considered as the source of this force. Two entirely different types of working stroke termination are considered. Along with the fluctuation mechanism, which controls the working stroke duration t w at isometric contraction, another interrupt mechanism is initially taken into account. It is triggered when the lever arm shift amounts to the maximal value S ≈ 11 nm, the back door opens, and Pi crashes out. As a result, t w becomes inversely proportional to the velocity v of sliding filaments t w ≈ S/v for a wide range of values of v. Principal features of the experimentally observed dependences of force, efficiency, and rate of heat production on velocity and ATP concentration can then be reproduced by fitting a single parameter: the velocity-independent time span t r between the termination of the last and beginning of the next working stroke. v becomes the principal variable of the model, and the muscle force changes under external load are determined by variations in v rather than in the tension of filaments. The Boltzmann equation for an ensemble of cross-bridges is obtained, and some collective effects are discussed.}, language = {en}, number = {9}, urldate = {2016-01-04}, journal = {European Biophysics Journal}, author = {Rosenfeld, E. V.}, month = aug, year = {2012}, keywords = {Actin-myosin, Biochemistry, general, Biophysics and Biological Physics, Cell Biology, Chemomechanical transduction, Membrane Biology, Muscle force, Nanotechnology, Neurobiology, Transient process}, pages = {733--753}, file = {Rosenfeld (2012) - The interrelation between mechanical characteristics of contracting muscle,.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NXKQAMH8\\Rosenfeld (2012) - The interrelation between mechanical characteristics of contracting muscle,.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6QWB5MA2\\s00249-012-0849-x.html:text/html} } @article{hajjar_cross-bridge_1992, title = {Cross-bridge dynamics in human ventricular myocardium. {Regulation} of contractility in the failing heart.}, volume = {86}, issn = {0009-7322, 1524-4539}, url = {http://circ.ahajournals.org.ezp.lib.unimelb.edu.au/content/86/6/1819}, doi = {10.1161/01.CIR.86.6.1819}, abstract = {BACKGROUND To investigate whether altered cross-bridge kinetics contribute to the contractile abnormalities observed in heart failure, we determined the mechanical properties of cardiac muscles from control and myopathic hearts. METHODS AND RESULTS Muscle fibers from normal (n = 5) and dilated cardiomyopathy (n = 6) hearts were obtained and chemically skinned with saponin. The muscles were then maximally activated at saturating calcium concentrations. Unloaded shortening velocities (V0) were determined in both groups. V0 in control was 0.72 +/- 0.09 Lmax/sec, whereas in myopathic muscles, V0 was 0.41 +/- 0.06 Lmax/sec at 22 degrees C. The muscles were also sinusoidally oscillated at frequencies ranging between 0.01 and 100 Hz. The dynamic stiffness of the muscles was calculated from the ratio of force response amplitude to length oscillation amplitude. At low frequencies ({\textless} 0.2 Hz) the stiffness was constant but was larger in myopathic muscles. In the range of 0.2-1 Hz, there was a drop in the magnitude of dynamic stiffness to approximately one quarter of the low-frequency baseline. This range reflects cross-bridge turnover kinetics. In control muscles, the frequency of minimum stiffness was 0.78 +/- 0.06 Hz, whereas it was 0.42 +/- 0.07 Hz in myopathic muscles. At higher frequencies, the dynamic stiffness increased and reached a plateau at 30 Hz. There were no differences in the plateau reached between control and myopathic muscles. CONCLUSIONS Because myopathic hearts have a markedly diminished energy reserve, the slowing of the cross-bridge cycling rate plays an important adaptational role in the observed contractility changes in human heart failure. Although the potential to generate maximal Ca(2+)-activated force is similar in normal and myopathic hearts, alterations in contractile protein composition could explain the diminished cross-bridge cycling rate in failing hearts.}, language = {en}, number = {6}, urldate = {2016-01-05}, journal = {Circulation}, author = {Hajjar, R. J. and Gwathmey, J. K.}, month = dec, year = {1992}, pmid = {1451254}, keywords = {Actin-myosin}, pages = {1819--1826}, file = {Hajjar_Gwathmey (1992) - Cross-bridge dynamics in human ventricular myocardium.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FTADCVFS\\Hajjar_Gwathmey (1992) - Cross-bridge dynamics in human ventricular myocardium.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TPWTRMZK\\1819.html:text/html} } @article{astumian_thermodynamics_2010, title = {Thermodynamics and {Kinetics} of {Molecular} {Motors}}, volume = {98}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349510003206}, doi = {10.1016/j.bpj.2010.02.040}, abstract = {Molecular motors are first and foremost molecules, governed by the laws of chemistry rather than of mechanics. The dynamical behavior of motors based on chemical principles can be described as a random walk on a network of states. A key insight is that any molecular motor in solution explores all possible motions and configurations at thermodynamic equilibrium. By using input energy and chemical design to prevent motion that is not wanted, what is left behind is the motion that is desired. This review is focused on two-headed motors such as kinesin and Myosin V that move on a polymeric track. By use of microscopic reversibility, it is shown that the ratio between the number of forward steps and the number of backward steps in any sufficiently long time period does not directly depend on the mechanical properties of the linker between the two heads. Instead, this ratio is governed by the relative chemical specificity of the heads in the front-versus-rear position for the fuel, adenosine triphosphate and its products, adenosine diphosphate and inorganic phosphate. These insights have been key factors in the design of biologically inspired synthetic molecular walkers constructed out of DNA or out of small organic molecules.}, number = {11}, urldate = {2016-01-04}, journal = {Biophysical Journal}, author = {Astumian, R. Dean}, month = jun, year = {2010}, keywords = {molecular motors}, pages = {2401--2409}, file = {Astumian (2010) - Thermodynamics and Kinetics of Molecular Motors.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UDD3P2HI\\Astumian (2010) - Thermodynamics and Kinetics of Molecular Motors.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\X4A8P2GU\\S0006349510003206.html:text/html} } @article{piazzesi_cross-bridge_1995, title = {A cross-bridge model that is able to explain mechanical and energetic properties of shortening muscle.}, volume = {68}, issn = {0006-3495}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1282100/}, abstract = {The responses of muscle to steady and stepwise shortening are simulated with a model in which actin-myosin cross-bridges cycle through two pathways distinct for the attachment-detachment kinetics and for the proportion of energy converted into work. Small step releases and steady shortening at low velocity (high load) favor the cycle implying approximately 5 nm sliding per cross-bridge interaction and approximately 100/s detachment-reattachment process; large step releases and steady shortening at high velocity (low load) favor the cycle implying approximately 10 nm sliding per cross-bridge interaction and approximately 20/s detachment-reattachment process. The model satisfactorily predicts specific mechanical properties of frog skeletal muscle, such as the rate of regeneration of the working stroke as measured by double-step release experiments and the transition to steady state during multiple step releases (staircase shortening). The rate of energy liberation under different mechanical conditions is correctly reproduced by the model. During steady shortening, the relation of energy liberation rate versus shortening speed attains a maximum (approximately 6 times the isometric rate) for shortening velocities lower than half the maximum velocity of shortening and declines for higher velocities. In addition, the model provides a clue for explaining how, in different muscle types, the higher the isometric maintenance heat, the higher the power output during steady shortening.}, number = {5}, urldate = {2016-01-05}, journal = {Biophysical Journal}, author = {Piazzesi, G and Lombardi, V}, month = may, year = {1995}, pmid = {7612839}, pmcid = {PMC1282100}, keywords = {Actin-myosin}, pages = {1966--1979}, file = {Piazzesi_Lombardi (1995) - A cross-bridge model that is able to explain mechanical and energetic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MHKAK4BV\\Piazzesi_Lombardi (1995) - A cross-bridge model that is able to explain mechanical and energetic.pdf:application/pdf} } @article{bustamante_mechanical_2004, title = {Mechanical {Processes} in {Biochemistry}}, volume = {73}, url = {http://dx.doi.org/10.1146/annurev.biochem.72.121801.161542}, doi = {10.1146/annurev.biochem.72.121801.161542}, abstract = {Mechanical processes are involved in nearly every facet of the cell cycle. Mechanical forces are generated in the cell during processes as diverse as chromosomal segregation, replication, transcription, translation, translocation of proteins across membranes, cell locomotion, and catalyzed protein and nucleic acid folding and unfolding, among others. Because force is a product of all these reactions, biochemists are beginning to directly apply external forces to these processes to alter the extent or even the fate of these reactions hoping to reveal their underlying molecular mechanisms. This review provides the conceptual framework to understand the role of mechanical force in biochemistry.}, number = {1}, urldate = {2016-01-08}, journal = {Annual Review of Biochemistry}, author = {Bustamante, Carlos and Chemla, Yann R. and Forde, Nancy R. and Izhaky, David}, year = {2004}, pmid = {15189157}, keywords = {enzyme catalysis, mechanical forces, mechanical unfolding, molecular motors, single-molecule manipulation}, pages = {705--748}, file = {Carlos Bustamante et al (2004) - Mechanical Processes in Biochemistry.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QQHEHNXT\\Carlos Bustamante et al (2004) - Mechanical Processes in Biochemistry.pdf:application/pdf} } @article{rice_approximate_2008, title = {Approximate {Model} of {Cooperative} {Activation} and {Crossbridge} {Cycling} in {Cardiac} {Muscle} {Using} {Ordinary} {Differential} {Equations}}, volume = {95}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S000634950878384X}, doi = {10.1529/biophysj.107.119487}, abstract = {We develop a point model of the cardiac myofilament (MF) to simulate a wide variety of experimental muscle characterizations including Force-Ca relations and twitches under isometric, isosarcometric, isotonic, and auxotonic conditions. Complex MF behaviors are difficult to model because spatial interactions cannot be directly implemented as ordinary differential equations. We therefore allow phenomenological approximations with careful consideration to the relationships with the underlying biophysical mechanisms. We describe new formulations that avoid mean-field approximations found in most existing MF models. To increase the scope and applicability of the model, we include length- and temperature-dependent effects that play important roles in MF responses. We have also included a representation of passive restoring forces to simulate isolated cell shortening protocols. Possessing both computational efficiency and the ability to simulate a wide variety of muscle responses, the MF representation is well suited for coupling to existing cardiac cell models of electrophysiology and Ca-handling mechanisms. To illustrate this suitability, the MF model is coupled to the Chicago rabbit cardiomyocyte model. The combined model generates realistic appearing action potentials, intracellular Ca transients, and cell shortening signals. The combined model also demonstrates that the feedback effects of force on Ca binding to troponin can modify the cytosolic Ca transient.}, number = {5}, urldate = {2016-01-05}, journal = {Biophysical Journal}, author = {Rice, John Jeremy and Wang, Fei and Bers, Donald M. and de Tombe, Pieter P.}, month = sep, year = {2008}, keywords = {Actin-myosin}, pages = {2368--2390}, file = {Rice et al (2008) - Approximate Model of Cooperative Activation and Crossbridge Cycling in Cardiac.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3WAMQS2H\\Rice et al (2008) - Approximate Model of Cooperative Activation and Crossbridge Cycling in Cardiac.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MVG8HPT7\\S000634950878384X.html:text/html} } @article{hill_theoretical_1974, title = {Theoretical formalism for the sliding filament model of contraction of striated muscle {Part} {I}}, volume = {28}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/0079610774900200}, doi = {10.1016/0079-6107(74)90020-0}, urldate = {2016-01-05}, journal = {Progress in Biophysics and Molecular Biology}, author = {Hill, Terrell L.}, month = jan, year = {1974}, keywords = {Actin-myosin}, pages = {267--340}, file = {Hill (1974) - Theoretical formalism for the sliding filament model of contraction of striated.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\M3N8HG9Z\\Hill (1974) - Theoretical formalism for the sliding filament model of contraction of striated.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KJDWEDZG\\0079610774900200.html:text/html} } @article{ebus_effects_2001, title = {Effects of {MgATP} on {ATP} utilization and force under normal and simulated ischaemic conditions in rat cardiac trabeculae}, volume = {443}, issn = {0031-6768, 1432-2013}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s004240100667}, doi = {10.1007/s004240100667}, abstract = {. The dependency of ATP utilization and isometric force on [MgATP] was studied in skinned rat trabeculae under normal (pH 7.0) and simulated ischaemic (pH 6.2, 30 mM added Pi) conditions at 20±1 °C. At saturating [Ca2+], mean (±SEM) ATP utilization at 5 mM MgATP (A 0) was 0.48±0.03 mM/s and force (F 0) was 37±2 kN/m2. At 10 µM MgATP under normal conditions ATP utilization decreased gradually to 66±3\% of A 0 , and force increased to 169±7\% of F 0. Under ischaemic conditions at 10 µM MgATP, ATP utilization decreased from 30±5\% to 11±2\% of A 0 whereas force increased eightfold from 12±4\% to 97±7\% of F 0. The [MgATP] at half-maximal ATP utilization (K m) under ischaemic conditions was 21±3 µM. At pH 7.0, K m was estimated to be less than 10 µM. These results show that tension cost decreases markedly with decreasing MgATP. Under ischaemic conditions parallel changes in Ca2+ sensitivity of force and ATP utilization were observed, corresponding to 1.3 pCa units. Reducing [MgATP] from 0.5 to 0.05 mM caused a modest reversal of this change in Ca2+ sensitivity. These changes in Ca2+ sensitivity are consistent with a marked reduction in active force and force-related ATP utilization during ischaemia but are insufficient to explain the ischaemic contracture on the basis of active force development.}, language = {en}, number = {1}, urldate = {2016-01-06}, journal = {Pflügers Archiv}, author = {Ebus, J. and Papp, Z. and Zaremba, R. and Stienen, G.}, month = aug, year = {2001}, keywords = {Cardiac muscle Adenosine triphosphatase ATP Ischaemia, Human Physiology, SERCA}, pages = {102--111}, file = {Ebus et al (2001) - Effects of MgATP on ATP utilization and force under normal and simulated.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\83RMI4IX\\Ebus et al (2001) - Effects of MgATP on ATP utilization and force under normal and simulated.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SREVFK8B\\s004240100667.html:text/html} } @article{loiselle_why_2010, title = {Why has reversal of the actin-myosin cross-bridge cycle not been observed experimentally?}, volume = {108}, copyright = {Copyright © 2010 the American Physiological Society}, issn = {8750-7587, 1522-1601}, url = {http://jap.physiology.org.ezp.lib.unimelb.edu.au/content/108/6/1465}, doi = {10.1152/japplphysiol.01198.2009}, abstract = {We trace the history of attempts to determine whether the experimentally observed diminution of metabolic energy expenditure when muscles lengthen during active contraction is consistent with reversibility of biochemical reactions and, in particular, with the regeneration of ATP. We note that this scientific endeavor has something of a parallel flavor to it, with both early and more recent experiments exploiting both isolated muscle preparations and exercising human subjects. In tracing this history from the late 19th century to the present, it becomes clear that energy can be (at least transiently) stored in a muscle undergoing an eccentric contraction but that this is unlikely to be due to the regeneration of ATP. A recently developed, thermodynamically constrained model of the cross-bridge cycle provides additional insight into this conclusion.}, language = {en}, number = {6}, urldate = {2016-01-06}, journal = {Journal of Applied Physiology}, author = {Loiselle, Denis S. and Tran, Kenneth and Crampin, Edmund J. and Curtin, Nancy A.}, month = jun, year = {2010}, pmid = {20133436}, keywords = {Actin-myosin}, pages = {1465--1471}, file = {Loiselle et al (2010) - Why has reversal of the actin-myosin cross-bridge cycle not been observed.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U66T8BS5\\Loiselle et al (2010) - Why has reversal of the actin-myosin cross-bridge cycle not been observed.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CK4JUM4R\\1465.html:text/html} } @article{barclay_estimation_1998, title = {Estimation of cross-bridge stiffness from maximum thermodynamic efficiency}, volume = {19}, issn = {0142-4319, 1573-2657}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1023/A%3A1005409708838}, doi = {10.1023/A:1005409708838}, abstract = {In muscle, work is performed by myosin cross-bridges during interactions with actin filaments. The amount of work performed during each interaction can be related to the mechanical properties of the cross-bridge; work is the integral of the force produced with respect to the distance that the cross-bridge moves the actin filament, and force is determined by the stiffness of the attached cross-bridge. In this paper, cross-bridge stiffness in frog sartorius muscle was estimated from thermodynamic efficiency (work/free energy change) using a two-state cross-bridge model, assuming constant stiffness over the working range and tight-coupling between cross- bridge cycles and ATP use. This model accurately predicts mechanical efficiency (work/enthalpy output). A critical review of the literature indicates that a realistic value for maximum thermodynamic efficiency of frog sartorius is 0.45 under conditions commonly used in experiments on isolated muscle. Cross-bridge stiffness was estimated for a range of power stroke amplitudes. For realistic amplitudes (10–15nm), estimated cross-bridge stiffness was between 1 and 2.2pNnm−1. These values are similar to those estimated from quick-release experiments, taking into account compliance arising from structures other than cross-bridges, but are substantially higher than those from isolated protein studies. The effects on stiffness estimates of relaxing the tight-coupling requirement and of incorporating more force-producing cross-bridge states are also considered.}, language = {en}, number = {8}, urldate = {2016-01-06}, journal = {Journal of Muscle Research \& Cell Motility}, author = {Barclay, C. J.}, month = nov, year = {1998}, keywords = {Actin-myosin, Animal Anatomy / Morphology / Histology, Cell Biology, Molecular Medicine, Proteomics}, pages = {855--864}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VT2C8JTU\\A1005409708838.html:text/html} } @article{romberg_chemomechanical_1993, title = {Chemomechanical cycle of kinesin differs from that of myosin}, volume = {361}, copyright = {© 1993 Nature Publishing Group}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v361/n6408/abs/361168a0.html}, doi = {10.1038/361168a0}, language = {en}, number = {6408}, urldate = {2016-01-15}, journal = {Nature}, author = {Romberg, Laura and Vale, Ronald D.}, month = jan, year = {1993}, keywords = {Actin-myosin, Kinesin, molecular motors}, pages = {168--170}, file = {Romberg_Vale (1993) - Chemomechanical cycle of kinesin differs from that of myosin.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NMZ5ZUVS\\Romberg_Vale (1993) - Chemomechanical cycle of kinesin differs from that of myosin.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R3M4IWX2\\361168a0.html:text/html} } @article{berridge_calcium_2003, title = {Calcium signalling: dynamics, homeostasis and remodelling}, volume = {4}, copyright = {© 2003 Nature Publishing Group}, issn = {1471-0072}, shorttitle = {Calcium signalling}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrm/journal/v4/n7/full/nrm1155.html}, doi = {10.1038/nrm1155}, abstract = {Ca2+ is a highly versatile intracellular signal that operates over a wide temporal range to regulate many different cellular processes. An extensive Ca2+-signalling toolkit is used to assemble signalling systems with very different spatial and temporal dynamics. Rapid highly localized Ca2+ spikes regulate fast responses, whereas slower responses are controlled by repetitive global Ca2+ transients or intracellular Ca2+ waves. Ca2+ has a direct role in controlling the expression patterns of its signalling systems that are constantly being remodelled in both health and disease.}, language = {en}, number = {7}, urldate = {2016-01-06}, journal = {Nature Reviews Molecular Cell Biology}, author = {Berridge, Michael J. and Bootman, Martin D. and Roderick, H. Llewelyn}, month = jul, year = {2003}, keywords = {Calcium signalling}, pages = {517--529}, file = {Berridge et al (2003) - Calcium signalling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QS6J9PS8\\Berridge et al (2003) - Calcium signalling.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TRU73ZRM\\nrm1155.html:text/html} } @article{meyer_calcium_1991, title = {Calcium {Spiking}}, volume = {20}, url = {http://dx.doi.org/10.1146/annurev.bb.20.060191.001101}, doi = {10.1146/annurev.bb.20.060191.001101}, number = {1}, urldate = {2016-01-06}, journal = {Annual Review of Biophysics and Biophysical Chemistry}, author = {Meyer, T and Stryer, L.}, year = {1991}, pmid = {1867714}, keywords = {Calcium signalling}, pages = {153--174} } @article{scoote_myocardial_2004, title = {Myocardial calcium signalling and arrhythmia pathogenesis}, volume = {322}, issn = {0006-291X}, url = {http://www.sciencedirect.com/science/article/pii/S0006291X04017723}, doi = {10.1016/j.bbrc.2004.08.034}, abstract = {Myocardial calcium signalling is a vital component of the normal physiological function of the heart. Key amongst the many roles calcium plays is its use as the primary signalling component of excitation–contraction coupling, the intracellular process that links cardiomyocyte depolarisation to contraction. Defective cellular calcium handling, due to abnormalities of the various components which mediate and control excitation–contraction coupling, is widely recognised as a significant patho-physiological event in the contractile dysfunction of the failing heart. In addition, similar defects also appear to be increasingly recognised as mediators of certain forms of cardiac arrhythmias. Such defects include single gene defects in excitation–contraction coupling components that lead to inherited sudden death arrhythmia syndromes. Alternatively, arrhythmogenesis occurring within the context of acquired cardiac disease, in particular heart failure, also appears to be highly dependent on abnormal calcium homeostasis. In this article we review the defects in cardiomyocyte calcium homeostasis that lead to particular pro-arrhythmogenic phenomena and discuss recent insights gained into a variety of inherited and acquired arrhythmia syndromes that appear to involve defective calcium signalling as a central component of their patho-physiology. Potential opportunities for new anti arrhythmic therapeutic strategies based on these recent insights are also discussed.}, number = {4}, urldate = {2016-01-06}, journal = {Biochemical and Biophysical Research Communications}, author = {Scoote, Mark and Williams, Alan J.}, month = oct, year = {2004}, keywords = {SERCA}, pages = {1286--1309}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VIWDCREP\\S0006291X04017723.html:text/html} } @article{cooling_sensitivity_2009, title = {Sensitivity of {NFAT} {Cycling} to {Cytosolic} {Calcium} {Concentration}: {Implications} for {Hypertrophic} {Signals} in {Cardiac} {Myocytes}}, volume = {96}, issn = {0006-3495}, shorttitle = {Sensitivity of {NFAT} {Cycling} to {Cytosolic} {Calcium} {Concentration}}, url = {http://www.sciencedirect.com/science/article/pii/S0006349509003099}, doi = {10.1016/j.bpj.2008.11.064}, abstract = {The nuclear factor of activated T-cell (NFAT) transcription factors play an important role in many biological processes, including pathological cardiac hypertrophy. Stimulated by calcium signals, NFAT is translocated to the nucleus where it can regulate hypertrophic genes (excitation-transcription coupling). In excitable cells, such as myocytes, calcium is a key second messenger for multiple signaling events, including excitation-contraction coupling. Whether the calcium signals due to excitation-contraction and excitation-transcription coupling coincide or how they can be differentiated is currently unclear. Here we construct a mathematical model of NFAT cycling fitted to skeletal myocyte and baby hamster kidney cell data. The model replicates key behavior with respect to sensitivity to calcineurin overexpression and to calcium oscillations. Finally, we measure the sensitivity of the system to a simulated hypertrophic calcium signal, against a background excitation-contraction coupling calcium oscillation. We find that NFAT cycling is sensitive to excitation-transcription coupling even when both calcium signals are in the same cellular compartment, thus showing that separation of the signals may not be necessary in vitro.}, number = {6}, urldate = {2016-01-06}, journal = {Biophysical Journal}, author = {Cooling, Michael T. and Hunter, Peter and Crampin, Edmund J.}, month = mar, year = {2009}, keywords = {Calcium signalling}, pages = {2095--2104}, file = {Cooling et al (2009) - Sensitivity of NFAT Cycling to Cytosolic Calcium Concentration.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QNCCES67\\Cooling et al (2009) - Sensitivity of NFAT Cycling to Cytosolic Calcium Concentration.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U7HJRU99\\S0006349509003099.html:text/html} } @article{roberts_functions_2013, title = {Functions and mechanics of dynein motor proteins}, volume = {14}, copyright = {© 2013 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, issn = {1471-0072}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrm/journal/v14/n11/abs/nrm3667.html}, doi = {10.1038/nrm3667}, abstract = {Fuelled by ATP hydrolysis, dyneins generate force and movement on microtubules in a wealth of biological processes, including ciliary beating, cell division and intracellular transport. The large mass and complexity of dynein motors have made elucidating their mechanisms a sizable task. Yet, through a combination of approaches, including X-ray crystallography, cryo-electron microscopy, single-molecule assays and biochemical experiments, important progress has been made towards understanding how these giant motor proteins work. From these studies, a model for the mechanochemical cycle of dynein is emerging, in which nucleotide-driven flexing motions within the AAA+ ring of dynein alter the affinity of its microtubule-binding stalk and reshape its mechanical element to generate movement. View full text}, language = {en}, number = {11}, urldate = {2016-01-15}, journal = {Nature Reviews Molecular Cell Biology}, author = {Roberts, Anthony J. and Kon, Takahide and Knight, Peter J. and Sutoh, Kazuo and Burgess, Stan A.}, month = nov, year = {2013}, keywords = {Cilia, Dynein, molecular motors, Structural biology}, pages = {713--726}, file = {Roberts et al (2013) - Functions and mechanics of dynein motor proteins.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6B7U4GA3\\Roberts et al (2013) - Functions and mechanics of dynein motor proteins.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2H5KE98H\\nrm3667.html:text/html} } @article{chowdhury_stochastic_2013, series = {Stochastic mechano-chemical kinetics of molecular motors: {A} multidisciplinary enterprise from a physicist’s perspective}, title = {Stochastic mechano-chemical kinetics of molecular motors: {A} multidisciplinary enterprise from a physicist’s perspective}, volume = {529}, issn = {0370-1573}, shorttitle = {Stochastic mechano-chemical kinetics of molecular motors}, url = {http://www.sciencedirect.com/science/article/pii/S0370157313001099}, doi = {10.1016/j.physrep.2013.03.005}, abstract = {A molecular motor is made of either a single macromolecule or a macromolecular complex. Just like their macroscopic counterparts, molecular motors “transduce” input energy into mechanical work. All the nano-motors considered here operate under isothermal conditions far from equilibrium. Moreover, one of the possible mechanisms of energy transduction, called Brownian ratchet, does not even have any macroscopic counterpart. But, molecular motor is not synonymous with Brownian ratchet; a large number of molecular motors execute a noisy power stroke, rather than operating as Brownian ratchet. We review not only the structural design and stochastic kinetics of individual single motors, but also their coordination, cooperation and competition as well as the assembly of multi-module motors in various intracellular kinetic processes. Although all the motors considered here execute mechanical movements, efficiency and power output are not necessarily good measures of performance of some motors. Among the intracellular nano-motors, we consider the porters, sliders and rowers, pistons and hooks, exporters, importers, packers and movers as well as those that also synthesize, manipulate and degrade “macromolecules of life”. We review mostly the quantitative models for the kinetics of these motors. We also describe several of those motor-driven intracellular stochastic processes for which quantitative models are yet to be developed. In part I, we discuss mainly the methodology and the generic models of various important classes of molecular motors. In part II, we review many specific examples emphasizing the unity of the basic mechanisms as well as diversity of operations arising from the differences in their detailed structure and kinetics. Multi-disciplinary research is presented here from the perspective of physicists.}, number = {1}, urldate = {2016-01-17}, journal = {Physics Reports}, author = {Chowdhury, Debashish}, month = aug, year = {2013}, keywords = {ATP, ATP synthase, Bacterial flagellar motor, Dynein, Enzyme, F-actin, Helicase, Ion-motive force, Kinesin, Microtubule, molecular motors, Motor protein, Myosin, Polymerase, Ribosome, Translocase}, pages = {1--197}, file = {Chowdhury (2013) - Stochastic mechano-chemical kinetics of molecular motors.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DAEPJ5TM\\Chowdhury (2013) - Stochastic mechano-chemical kinetics of molecular motors.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CCS9KAVN\\S0370157313001099.html:text/html} } @article{chowdhury_michaelismenten_2014, title = {Michaelis–{Menten} at 100 and allosterism at 50: driving molecular motors in a hailstorm with noisy {ATPase} engines and allosteric transmission}, volume = {281}, issn = {1742-4658}, shorttitle = {Michaelis–{Menten} at 100 and allosterism at 50}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/febs.12596/abstract}, doi = {10.1111/febs.12596}, abstract = {Cytoskeletal motor proteins move on filamentous tracks by converting input chemical energy that they derive by catalyzing the hydrolysis of ATP. The ATPase site is the analogue of an engine and hydrolysis of ATP is the analogue of burning of chemical fuel. Moreover, the functional role of a segment of the motor is analogous to that of the transmission system of an automobile, which consists of a shaft, gear, clutch, etc. The operation of the engine is intrinsically ‘noisy’ and the motor faces a molecular ‘hailstorm’ in the aqueous medium. In this commemorative review, we celebrate the centenary of Michaelis and Menten's landmark paper of 1913 and the golden jubilee of Monod and colleagues classic paper of 1963 by highlighting their relevance with respect to explaining the operational mechanisms of the engine and the transmission system, respectively, of cytoskeletal motors.}, language = {en}, number = {2}, urldate = {2016-01-18}, journal = {FEBS Journal}, author = {Chowdhury, Debashish}, month = jan, year = {2014}, keywords = {actin, allostery, ATP, cytoskeleton, dwell time, Enzyme, Michaelis-Menten, Microtubule, molecular motors, Motor protein, turnover time}, pages = {601--611}, file = {Chowdhury (2014) - Michaelis–Menten at 100 and allosterism at 50.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IDGEGW4W\\Chowdhury (2014) - Michaelis–Menten at 100 and allosterism at 50.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W57P98DP\\abstract.html:text/html} } @article{pinz_compromised_2011, title = {Compromised {Myocardial} {Energetics} in {Hypertrophied} {Mouse} {Hearts} {Diminish} the {Beneficial} {Effect} of {Overexpressing} {SERCA}2a}, volume = {286}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/286/12/10163}, doi = {10.1074/jbc.M110.210757}, abstract = {The sarcoplasmic reticulum calcium ATPase (SERCA) plays a central role in regulating intracellular Ca2+ homeostasis and myocardial contractility. Several studies show that improving Ca2+ handling in hypertrophied rodent hearts by increasing SERCA activity results in enhanced contractile function. This suggests that SERCA is a potential target for gene therapy in cardiac hypertrophy and failure. However, it raises the issue of increased energy cost resulting from a higher ATPase activity. In this study, we determined whether SERCA overexpression alters the energy cost of increasing myocardial contraction in mouse hearts with pressure-overload hypertrophy using 31P NMR spectroscopy. We isolated and perfused mouse hearts from wild-type (WT) and transgenic (TG) mice overexpressing the cardiac isoform of SERCA (SERCA2a) 8 weeks after ascending aortic constriction (left ventricular hypertrophy (LVH)) or sham operation. We found that overexpressing SERCA2a enhances myocardial contraction and relaxation in normal mouse hearts during inotropic stimulation with isoproterenol. Energy consumption was proportionate to the increase in contractile function. Thus, increasing SERCA2a expression in the normal heart allows an enhanced inotropic response with no compromise in energy supply and demand. However, this advantage was not sustained in LVH hearts in which the energetic status was compromised. Although the overexpression of SERCA2a prevented the down-regulation of SERCA protein in LVH hearts, TG-LVH hearts showed no increase in inotropic response when compared with WT-LVH hearts. Our results suggest that energy supply may be a limiting factor for the benefit of SERCA overexpression in hypertrophied hearts. Thus, strategies combining energetic support with increasing SERCA activity may improve the therapeutic effectiveness for heart failure.}, language = {en}, number = {12}, urldate = {2016-01-18}, journal = {Journal of Biological Chemistry}, author = {Pinz, Ilka and Tian, Rong and Belke, Darrell and Swanson, Eric and Dillmann, Wolfgang and Ingwall, Joanne S.}, month = mar, year = {2011}, pmid = {21278384}, keywords = {calcium, Calcium ATPase, Cardiac Hypertrophy, Cardiac Muscle, Energetics, Myocardial Contraction, NMR, SERCA, SERCA2a}, pages = {10163--10168}, file = {Pinz et al (2011) - Compromised Myocardial Energetics in Hypertrophied Mouse Hearts Diminish the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZZ3GR8Z5\\Pinz et al (2011) - Compromised Myocardial Energetics in Hypertrophied Mouse Hearts Diminish the.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4RR5KG2C\\10163.html:text/html} } @article{kawase_cardiac_2008, title = {The cardiac sarcoplasmic/endoplasmic reticulum calcium {ATPase}: a potent target for cardiovascular diseases}, volume = {5}, copyright = {© 2008 Nature Publishing Group}, issn = {1743-4297}, shorttitle = {The cardiac sarcoplasmic/endoplasmic reticulum calcium {ATPase}}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrcardio/journal/v5/n9/full/ncpcardio1301.html}, doi = {10.1038/ncpcardio1301}, abstract = {The cardiac isoform of the sarcoplasmic/endoplasmic reticulum calcium ATPase (SERCA2a) is a calcium ion (Ca2+) pump powered by ATP hydrolysis. SERCA2a transfers Ca2+ from the cytosol of the cardiomyocyte to the lumen of the sarcoplasmic reticulum during muscle relaxation. As such, this transporter has a key role in cardiomyocyte Ca2+ regulation. In both experimental models and human heart failure, SERCA2a expression is significantly decreased, which leads to abnormal Ca2+ handling and a deficient contractile state. Following a long line of investigations in isolated cardiac myocytes and small and large animal models, a clinical trial is underway that is restoring SERCA2a expression in patients with heart failure by use of adeno-associated virus type 1. Beyond its role in contractile abnormalities in heart failure, SERCA2a overexpression has beneficial effects in a host of other cardiovascular diseases. Here we describe the mechanism of Ca2+ regulation by SERCA2a, examine the beneficial effects as well as the failures, risks and complexities associated with SERCA2a overexpression, and discuss the potential of SERCA2a as a target for the treatment of cardiovascular disease.}, language = {en}, number = {9}, urldate = {2016-01-18}, journal = {Nature Clinical Practice Cardiovascular Medicine}, author = {Kawase, Yoshiaki and Hajjar, Roger J.}, year = {2008}, keywords = {arrhythmia, heart failure, mechanoenergetics, sarcoplasmic reticulum ATPase, SERCA, vascular smooth muscle cells}, pages = {554--565}, file = {Kawase_Hajjar (2008) - The cardiac sarcoplasmic-endoplasmic reticulum calcium ATPase.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\43W625R9\\Kawase_Hajjar (2008) - The cardiac sarcoplasmic-endoplasmic reticulum calcium ATPase.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\B3D4JA4I\\ncpcardio1301.html:text/html} } @article{bers_sarcoplasmic_2003, title = {Sarcoplasmic {Reticulum} {Ca}2+ and {Heart} {Failure} {Roles} of {Diastolic} {Leak} and {Ca}2+ {Transport}}, volume = {93}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/93/6/487}, doi = {10.1161/01.RES.0000091871.54907.6B}, language = {en}, number = {6}, urldate = {2016-01-18}, journal = {Circulation Research}, author = {Bers, Donald M. and Eisner, David A. and Valdivia, Héctor H.}, month = sep, year = {2003}, pmid = {14500331}, keywords = {calcium sparks, heart failure, ryanodine receptors, SERCA}, pages = {487--490}, file = {Bers et al (2003) - Sarcoplasmic Reticulum Ca2+ and Heart Failure Roles of Diastolic Leak and Ca2+.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G76CJXEU\\Bers et al (2003) - Sarcoplasmic Reticulum Ca2+ and Heart Failure Roles of Diastolic Leak and Ca2+.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SCBPHQWR\\487.html:text/html} } @article{arai_sarcoplasmic_1994, title = {Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.}, volume = {74}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/74/4/555}, doi = {10.1161/01.RES.74.4.555}, language = {en}, number = {4}, urldate = {2016-01-18}, journal = {Circulation Research}, author = {Arai, M. and Matsui, H. and Periasamy, M.}, month = apr, year = {1994}, pmid = {8137493}, keywords = {SERCA}, pages = {555--564}, file = {Arai et al (1994) - Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D3IJ76SG\\Arai et al (1994) - Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.pdf:application/pdf;Arai et al (1994) - Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V4XZRDSF\\Arai et al (1994) - Sarcoplasmic reticulum gene expression in cardiac hypertrophy and heart failure.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MGQ2TAKX\\555.html:text/html;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\38VX6KCT\\555.html:text/html} } @article{gould_kinetic_1986, title = {A kinetic model for the {Ca}2+ + {Mg}2+-activated {ATPase} of sarcoplasmic reticulum.}, volume = {237}, issn = {0264-6021}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1146968/}, abstract = {The Ca2+ + Mg2+-activated ATPase of sarcoplasmic reticulum exhibits complex kinetics of activation with respect to ATP. ATPase activity is pH-dependent, with similar pH-activity profiles at high and low concentrations of ATP. Low concentrations of Ca2+ in the micromolar range activate the ATPase, whereas activity is inhibited by Ca2+ at millimolar concentrations. The pH-dependence of this Ca2+ inhibition and the effect of the detergent C12E8 (dodecyl octaethylene glycol monoether) on Ca2+ inhibition are similar to those observed on activation by low concentrations of Ca2+. On the basis of these and other studies we present a kinetic model for the ATPase. The ATPase is postulated to exist in one of two conformations: a conformation (E1) of high affinity for Ca2+ and MgATP and a conformation (E2) of low affinity for Ca2+ and MgATP. Ca2+ binding to E2 and to the phosphorylated form E2P are equal. Proton binding at the Ca2+-binding sites in the E1 and E2 conformations explains the pH-dependence of Ca2+ effects. Binding of MgATP to the phosphorylated intermediate E1'PCa2 and to E2 modulate the rates of the transport step E1'PCa-E2'PCa2 and the return of the empty Ca2+ sites to the outside surface of the sarcoplasmic reticulum, as well as the rate of dephosphorylation of E2P. Only a single binding site for MgATP is postulated.}, number = {1}, urldate = {2016-01-18}, journal = {Biochemical Journal}, author = {Gould, G W and East, J M and Froud, R J and McWhirter, J M and Stefanova, H I and Lee, A G}, month = jul, year = {1986}, pmid = {2948490}, pmcid = {PMC1146968}, keywords = {SERCA}, pages = {217--227} } @article{haynes_computer_1987, title = {Computer modeling of {Ca} 2+ pump function of {Ca} 2+- {Mg} 2+-{ATPase} of sarcoplasmic reticulum}, volume = {67}, url = {http://physrev.physiology.org.ezp.lib.unimelb.edu.au/content/physrev/67/1/244.full.pdf}, urldate = {2016-01-18}, journal = {Physiol. Rev}, author = {Haynes, DUNCAN H. and Mandveno, ALAN}, year = {1987}, keywords = {SERCA}, pages = {244--284}, file = {Haynes_Mandveno (1987) - Computer modeling of Ca 2+ pump function of Ca 2+- Mg 2+-ATPase of sarcoplasmic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JX8K4T9S\\Haynes_Mandveno (1987) - Computer modeling of Ca 2+ pump function of Ca 2+- Mg 2+-ATPase of sarcoplasmic.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I3JCU64E\\obrareq.html:text/html} } @article{lytton_functional_1992, title = {Functional comparisons between isoforms of the sarcoplasmic or endoplasmic reticulum family of calcium pumps.}, volume = {267}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/267/20/14483}, abstract = {ATP-dependent calcium pumps that reside in intracellular organelles are encoded by a family of structurally related enzymes, termed the sarcoplasmic or endoplasmic reticulum Ca(2+)-ATPases (SERCA), which each have a distinct pattern of tissue-specific and developmentally regulated expression. A COS-1 cell expression system was used to examine the biochemical properties of the isoforms: SERCA1 (fast-twitch skeletal muscle). SERCA2a (cardiac/slow-twitch skeletal muscle), SERCA2b (ubiquitous smooth- and non-muscle), and SERCA3 (non-muscle). Each isoform was expressed efficiently and appeared to be targeted to the endoplasmic reticulum. All isoforms displayed qualitatively similar enzymatic properties and were activated by calcium in a cooperative manner with a Hill coefficient of 2. The quantitative properties of SERCA1 and SERCA2a (the muscle isoforms) were identical in all respects. SERCA2b, however, appeared to have a lower turnover rate for both calcium transport and ATP hydrolysis. SERCA3 displayed a reduced apparent affinity for calcium, an increased apparent affinity for vanadate, and an altered pH dependence when compared with the other isoforms. These properties are consistent with an enzyme in which the equilibrium between the E1 and E2 conformations is shifted toward the E2 state.}, language = {en}, number = {20}, urldate = {2016-01-18}, journal = {Journal of Biological Chemistry}, author = {Lytton, J. and Westlin, M. and Burk, S. E. and Shull, G. E. and MacLennan, D. H.}, month = jul, year = {1992}, pmid = {1385815}, keywords = {SERCA}, pages = {14483--14489}, file = {Lytton et al (1992) - Functional comparisons between isoforms of the sarcoplasmic or endoplasmic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\27T75EZ5\\Lytton et al (1992) - Functional comparisons between isoforms of the sarcoplasmic or endoplasmic.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7CBQRQEQ\\14483.html:text/html} } @article{soh_network_2010, series = {Ecology and industrial microbiology • {Special} section: {Systems} biology}, title = {Network thermodynamics in the post-genomic era}, volume = {13}, issn = {1369-5274}, url = {http://www.sciencedirect.com/science/article/pii/S1369527410000421}, doi = {10.1016/j.mib.2010.03.001}, abstract = {Network models have been used to study the underlying processes and principles of biological systems for decades, providing many insights into the complexity of life. Biological systems require a constant flow of free energy to drive these processes that operate away from thermodynamic equilibrium. With the advent of high-throughput omics technologies, more and more thermodynamic knowledge about the biological components, processes and their interactions are surfacing that we can integrate using large-scale biological network models. This allows us to ask many fundamental questions about these networks, such as, how far away from equilibrium must the reactions in a network be displaced in order to allow growth, or what are the possible thermodynamic objectives of the cell.}, number = {3}, urldate = {2016-01-18}, journal = {Current Opinion in Microbiology}, author = {Soh, Keng Cher and Hatzimanikatis, Vassily}, month = jun, year = {2010}, keywords = {Physical biochemistry}, pages = {350--357}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I3Q467CJ\\S1369527410000421.html:text/html;Soh_Hatzimanikatis (2010) - Network thermodynamics in the post-genomic era.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9VCI93IB\\Soh_Hatzimanikatis (2010) - Network thermodynamics in the post-genomic era.pdf:application/pdf} } @article{price_candidate_2006, title = {Candidate {States} of {Helicobacter} pylori’s {Genome}-{Scale} {Metabolic} {Network} upon {Application} of “{Loop} {Law}” {Thermodynamic} {Constraints}}, volume = {90}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349506725759}, doi = {10.1529/biophysj.105.072645}, abstract = {Constraint-based modeling has proven to be a useful tool in the analysis of biochemical networks. To date, most studies in this field have focused on the use of linear constraints, resulting from mass balance and capacity constraints, which lead to the definition of convex solution spaces. One additional constraint arising out of thermodynamics is known as the “loop law” for reaction fluxes, which states that the net flux around a closed biochemical loop must be zero because no net thermodynamic driving force exists. The imposition of the loop-law can lead to nonconvex solution spaces making the analysis of the consequences of its imposition challenging. A four-step approach is developed here to apply the loop-law to study metabolic network properties: 1), determine linear equality constraints that are necessary (but not necessarily sufficient) for thermodynamic feasibility; 2), tighten Vmax and Vmin constraints to enclose the remaining nonconvex space; 3), uniformly sample the convex space that encloses the nonconvex space using standard Monte Carlo techniques; and 4), eliminate from the resulting set all solutions that violate the loop-law, leaving a subset of steady-state solutions. This subset of solutions represents a uniform random sample of the space that is defined by the additional imposition of the loop-law. This approach is used to evaluate the effect of imposing the loop-law on predicted candidate states of the genome-scale metabolic network of Helicobacter pylori.}, number = {11}, urldate = {2016-01-18}, journal = {Biophysical Journal}, author = {Price, Nathan D. and Thiele, Ines and Palsson, Bernhard Ø.}, month = jun, year = {2006}, keywords = {Physical biochemistry}, pages = {3919--3928}, file = {Price et al (2006) - Candidate States of Helicobacter pylori’s Genome-Scale Metabolic Network upon.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JIISVQ8F\\Price et al (2006) - Candidate States of Helicobacter pylori’s Genome-Scale Metabolic Network upon.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WR3XVVZB\\S0006349506725759.html:text/html} } @article{kural_kinesin_2005, title = {Kinesin and {Dynein} {Move} a {Peroxisome} in {Vivo}: {A} {Tug}-of-{War} or {Coordinated} {Movement}?}, volume = {308}, copyright = {American Association for the Advancement of Science}, issn = {0036-8075, 1095-9203}, shorttitle = {Kinesin and {Dynein} {Move} a {Peroxisome} in {Vivo}}, url = {http://science.sciencemag.org.ezp.lib.unimelb.edu.au/content/308/5727/1469}, doi = {10.1126/science.1108408}, abstract = {We used fluorescence imaging with one nanometer accuracy (FIONA) to analyze organelle movement by conventional kinesin and cytoplasmic dynein in a cell. We located a green fluorescence protein (GFP)–tagged peroxisome in cultured Drosophila S2 cells to within 1.5 nanometers in 1.1 milliseconds, a 400-fold improvement in temporal resolution, sufficient to determine the average step size to be ∼8 nanometers for both dynein and kinesin. Furthermore, we found that dynein and kinesin do not work against each other in vivo during peroxisome transport. Rather, multiple kinesins or multiple dyneins work together, producing up to 10 times the in vitro speed. High-resolution images of organelles moving along cytoskeletal tracks in living cells show that different motors drive the forward and backward motion, with only one type operating at a time. High-resolution images of organelles moving along cytoskeletal tracks in living cells show that different motors drive the forward and backward motion, with only one type operating at a time.}, language = {en}, number = {5727}, urldate = {2016-01-18}, journal = {Science}, author = {Kural, Comert and Kim, Hwajin and Syed, Sheyum and Goshima, Gohta and Gelfand, Vladimir I. and Selvin, Paul R.}, month = jun, year = {2005}, pmid = {15817813}, keywords = {molecular motors}, pages = {1469--1472}, file = {Kural et al (2005) - Kinesin and Dynein Move a Peroxisome in Vivo.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V24D5FXV\\Kural et al (2005) - Kinesin and Dynein Move a Peroxisome in Vivo.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7GFV5AXF\\1469.html:text/html} } @article{hoffman_dynamic_2011, title = {Dynamic molecular processes mediate cellular mechanotransduction}, volume = {475}, copyright = {© 2011 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, issn = {0028-0836}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v475/n7356/abs/nature10316.html}, doi = {10.1038/nature10316}, abstract = {Cellular responses to mechanical forces are crucial in embryonic development and adult physiology, and are involved in numerous diseases, including atherosclerosis, hypertension, osteoporosis, muscular dystrophy, myopathies and cancer. These responses are mediated by load-bearing subcellular structures, such as the plasma membrane, cell-adhesion complexes and the cytoskeleton. Recent work has demonstrated that these structures are dynamic, undergoing assembly, disassembly and movement, even when ostensibly stable. An emerging insight is that transduction of forces into biochemical signals occurs within the context of these processes. This framework helps to explain how forces of varying strengths or dynamic characteristics regulate distinct signalling pathways. View full text}, language = {en}, number = {7356}, urldate = {2016-01-20}, journal = {Nature}, author = {Hoffman, Brenton D. and Grashoff, Carsten and Schwartz, Martin A.}, month = jul, year = {2011}, keywords = {Biophysics, Cell Biology, Chemomechanical transduction}, pages = {316--323}, file = {Hoffman et al (2011) - Dynamic molecular processes mediate cellular mechanotransduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IBA8JXT3\\Hoffman et al (2011) - Dynamic molecular processes mediate cellular mechanotransduction.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EXSR558B\\nature10316.html:text/html} } @article{tewari_computational_2015, title = {Computational {Model} of {Cross}-{Bridge} {Cycling} and {Force} {Generation} to {Explain} the {Effect} of {Metabolites} on {Cardiac} {Muscle} {Mechanics}}, volume = {108}, issn = {0006-3495}, url = {http://www.cell.com/article/S0006349514036376/abstract}, doi = {10.1016/j.bpj.2014.11.2425}, language = {English}, number = {2}, urldate = {2016-01-20}, journal = {Biophysical Journal}, author = {Tewari, Shivendra and Bugenhagen, Scott and Palmer, Bradley and Beard, Daniel}, month = jan, year = {2015}, keywords = {Actin-myosin}, pages = {444a}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VWUPR6ZW\\S0006-3495(14)03637-6.html:text/html;Tewari et al (2015) - Computational Model of Cross-Bridge Cycling and Force Generation to Explain the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AH48K4U2\\Tewari et al (2015) - Computational Model of Cross-Bridge Cycling and Force Generation to Explain the.pdf:application/pdf} } @article{tewari_dynamics_2015, title = {Dynamics of cross-bridge cycling, {ATP} hydrolysis, force generation, and deformation in cardiac muscle}, issn = {0022-2828}, url = {http://www.sciencedirect.com/science/article/pii/S0022282815000437}, doi = {10.1016/j.yjmcc.2015.02.006}, abstract = {Despite extensive study over the past six decades the coupling of chemical reaction and mechanical processes in muscle dynamics is not well understood. We lack a theoretical description of how chemical processes (metabolite binding, ATP hydrolysis) influence and are influenced by mechanical processes (deformation and force generation). To address this need, a mathematical model of the muscle cross-bridge (XB) cycle based on Huxley's sliding filament theory is developed that explicitly accounts for the chemical transformation events and the influence of strain on state transitions. The model is identified based on elastic and viscous moduli data from mouse and rat myocardial strips over a range of perturbation frequencies, and MgATP and inorganic phosphate (Pi) concentrations. Simulations of the identified model reproduce the observed effects of MgATP and MgADP on the rate of force development. Furthermore, simulations reveal that the rate of force re-development measured in slack–restretch experiments is not directly proportional to the rate of XB cycling. For these experiments, the model predicts that the observed increase in the rate of force generation with increased Pi concentration is due to inhibition of cycle turnover by Pi. Finally, the model captures the observed phenomena of force yielding suggesting that it is a result of rapid detachment of stretched attached myosin heads.}, urldate = {2016-01-20}, journal = {Journal of Molecular and Cellular Cardiology}, author = {Tewari, Shivendra G. and Bugenhagen, Scott M. and Palmer, Bradley M. and Beard, Daniel A.}, year = {2015}, keywords = {Actin-myosin, Cardiac Muscle, Cross-bridge cycle, Force generation, Metabolites, Sinusoidal perturbation analysis, Viscoelasticity}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6WUN2SK8\\S0022282815000437.html:text/html;Tewari et al - Dynamics of cross-bridge cycling, ATP hydrolysis, force generation, and.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\T6RRM69Q\\Tewari et al - Dynamics of cross-bridge cycling, ATP hydrolysis, force generation, and.pdf:application/pdf} } @article{ingber_integrins_1991, title = {Integrins as mechanochemical transducers}, volume = {3}, issn = {0955-0674}, url = {http://www.sciencedirect.com/science/article/pii/0955067491900587}, doi = {10.1016/0955-0674(91)90058-7}, abstract = {A recent resurgence of interest in mechanical forces and cell shape as biological regulators has revealed extracellular matrix as the site at which forces are transmitted both to and from cells. At the same time, great advances have been made in terms of defining cell-surface integrin receptors as transmembrane molecules that mediate cell attachment and physically interlink extracellular matrix with the intracellular cytoskeleton. Convergence of these two lines of research has begun to elucidate the molecular mechanism by which cells sense physical forces and transduce mechanical signals into a biochemical response.}, number = {5}, urldate = {2016-01-21}, journal = {Current Opinion in Cell Biology}, author = {Ingber, Donald}, month = oct, year = {1991}, keywords = {Chemomechanical transduction}, pages = {841--848}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FJ9NFNR5\\0955067491900587.html:text/html} } @article{le_rolle_bond_2005, title = {A {Bond} {Graph} {Model} of the {Cardiovascular} {System}}, volume = {53}, issn = {0001-5342, 1572-8358}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s10441-005-4881-4}, doi = {10.1007/s10441-005-4881-4}, abstract = {The study of the autonomic nervous system (ANS) function has shown to provide useful indicators for risk stratification and early detection on a variety of cardiovascular pathologies. However, data gathered during different tests of the ANS are difficult to analyse, mainly due to the complex mechanisms involved in the autonomic regulation of the cardiovascular system (CVS). Although model-based analysis of ANS data has been already proposed as a way to cope with this complexity, only a few models coupling the main elements involved have been presented in the literature. In this paper, a new model of the CVS, representing the ventricles, the circulatory system and the regulation of the CVS activity by the ANS, is presented. The models of the vascular system and the ventricular activity have been developed using the Bond Graph formalism, as it proposes a unified representation for all energetic domains, facilitating the integration of mechanic and hydraulic phenomena. In order to take into account the electro-mechanical behaviour of both ventricles, an electrophysiologic model of the cardiac action potential, represented by a set of ordinary differential equations, has been integrated. The short-term ANS regulation of heart rate, cardiac contractility and peripheral vasoconstriction is represented by means of continuous transfer functions. These models, represented in different continuous formalisms, are coupled by using a multi-formalism simulation library. Results are presented for two different autonomic tests, namely the Tilt Test and the Valsalva Manoeuvre, by comparing real and simulated signals.}, language = {en}, number = {4}, urldate = {2016-01-21}, journal = {Acta Biotheoretica}, author = {Le Rolle, V. and Hernandez, A. I. and Richard, P. Y. and Buisson, J. and Carrault, G.}, month = dec, year = {2005}, keywords = {biomedical systems, bond graphs, cardiovascular system, Evolutionary Biology, multi-formalism modelling, Philosophy of Biology}, pages = {295--312}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DMB8V6GP\\s10441-005-4881-4.html:text/html} } @article{ishida_fluid_1997, title = {Fluid {Shear} {Stress}-{Mediated} {Signal} {Transduction}: {How} {Do} {Endothelial} {Cells} {Transduce} {Mechanical} {Force} into {Biological} {Responses}?}, volume = {811}, issn = {1749-6632}, shorttitle = {Fluid {Shear} {Stress}-{Mediated} {Signal} {Transduction}}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/j.1749-6632.1997.tb51984.x/abstract}, doi = {10.1111/j.1749-6632.1997.tb51984.x}, language = {en}, number = {1}, urldate = {2016-01-21}, journal = {Annals of the New York Academy of Sciences}, author = {Ishida, Takafumi and Takahashi, Masafumi and Corson, Marshall A. and Berk, Bradford C.}, month = apr, year = {1997}, keywords = {Chemomechanical transduction}, pages = {12--24}, file = {Ishida et al (1997) - Fluid Shear Stress-Mediated Signal Transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\K4H68W6J\\Ishida et al (1997) - Fluid Shear Stress-Mediated Signal Transduction.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SJBGI7J4\\abstract.html:text/html} } @article{sachs_mechanical_1991, title = {Mechanical transduction by membrane ion channels: a mini review}, volume = {104}, issn = {0300-8177, 1573-4919}, shorttitle = {Mechanical transduction by membrane ion channels}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF00229804}, doi = {10.1007/BF00229804}, abstract = {There are ion channels in the cell membrane that are sensitive to stress in the membrane cytoskeleton. Some channels turn on with stress, others turn off. In specialized receptors such as those involved in hearing, touch, etc. the role of the channels is clear. However, virtually all cells have these channels, and we don't yet know the physiological role of the channels although it is reasonable to suppose that they are involved in the control of cell size, either acutely as in volume regulation, or trophically as in the control of cell division.}, language = {en}, number = {1-2}, urldate = {2016-01-21}, journal = {Molecular and Cellular Biochemistry}, author = {Sachs, F.}, month = may, year = {1991}, keywords = {Biochemistry, general, Cardiology, Chemomechanical transduction, ion channels, mechanical, Medical Biochemistry, membrane, Oncology, stress, transduction, volume}, pages = {57--60}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZXQIDTPK\\BF00229804.html:text/html} } @article{ji_serca1a_1999, title = {{SERCA}1a can functionally substitute for {SERCA}2a in the heart}, volume = {276}, copyright = {Copyright © 1999 the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/276/1/H89}, abstract = {We recently generated a transgenic (TG) mouse model in which the fast-twitch skeletal muscle sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA1a) is overexpressed in the heart. Ectopic overexpression of SERCA1a results in remodeling of the cardiac SR containing 80\% SERCA1a and 20\% endogenous SERCA2a with an ∼2.5-fold increase in the total amount of SERCA protein (E. Loukianov et al. Circ. Res. 83: 889–897, 1998). We have analyzed the Ca2+ transport properties of membranes from SERCA1a TG hearts in comparison to control hearts. Our data show that the maximal velocity of SR Ca2+ transport was significantly increased (∼1.9-fold) in TG hearts, whereas the apparent affinity of the SERCA pump for Ca2+ was not changed. Addition of phospholamban antibody in the Ca2+ uptake assays increased the apparent affinity for Ca2+ to the same extent in TG and non-TG (NTG) hearts, suggesting that phospholamban regulates the SERCA1a pump in TG hearts. Analysis of SERCA enzymatic properties in TG hearts revealed that the SERCA pump affinity for ATP, the Hill coefficient, the pH dependence of Ca2+ uptake, and the effect of acidic pH on Ca2+ transport were similar to those of NTG hearts. Interestingly, the rate constant of phosphoenzyme decay (turnover rate of SERCA enzyme) was also very similar between TG and NTG hearts. Together these findings suggest that1) the SERCA1a pump can functionally substitute for SERCA2a and is regulated by endogenous phospholamban in the heart and 2) SERCA1a exhibits several enzymatic properties similar to those of SERCA2a when expressed in a cardiac setting.}, language = {en}, number = {1}, urldate = {2016-01-22}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Ji, Yong and Loukianov, Evgeny and Loukianova, Tanya and Jones, Larry R. and Periasamy, Muthu}, month = jan, year = {1999}, pmid = {9887021}, keywords = {SERCA}, pages = {H89--H97}, file = {Ji et al (1999) - SERCA1a can functionally substitute for SERCA2a in the heart.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZTIKKQ37\\Ji et al (1999) - SERCA1a can functionally substitute for SERCA2a in the heart.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\54PX6HJS\\H89.html:text/html} } @article{gillespie_molecular_2001, title = {Molecular basis of mechanosensory transduction}, volume = {413}, copyright = {© 2001 Nature Publishing Group}, issn = {0028-0836}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v413/n6852/full/413194a0.html}, doi = {10.1038/35093011}, abstract = {Mechanotransduction — a cell's conversion of a mechanical stimulus into an electrical signal — reveals vital features of an organism's environment. From hair cells and skin mechanoreceptors in vertebrates, to bristle receptors in flies and touch receptors in worms, mechanically sensitive cells are essential in the life of an organism. The scarcity of these cells and the uniqueness of their transduction mechanisms have conspired to slow molecular characterization of the ensembles that carry out mechanotransduction. But recent progress in both invertebrates and vertebrates is beginning to reveal the identities of proteins essential for transduction.}, language = {en}, number = {6852}, urldate = {2016-01-21}, journal = {Nature}, author = {Gillespie, Peter G. and Walker, Richard G.}, month = sep, year = {2001}, keywords = {Chemomechanical transduction}, pages = {194--202}, file = {Gillespie_Walker (2001) - Molecular basis of mechanosensory transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IAFNA83X\\Gillespie_Walker (2001) - Molecular basis of mechanosensory transduction.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6CCTUG4E\\413194a0.html:text/html} } @article{cowin_candidates_1991, title = {Candidates for the {Mechanosensory} {System} in {Bone}}, volume = {113}, issn = {0148-0731}, url = {http://dx.doi.org/10.1115/1.2891234}, doi = {10.1115/1.2891234}, abstract = {Some potential mechanisms by which bone cells sense mechanical loads are described and hypotheses concerning the functioning of these mechanisms are explored. It is well known that bone tissue adapts its structure to its mechanical load environment. Recent research has illuminated the biological response of bone to mechanical loading at the cellular level, but the precise mechanosensory system that signals bone cells to deposit or resorb tissue has not been identifed. The purpose of this paper is to describe the current status of this research and to suggest some possible mechanosensory systems by which bone cells might sense environmental loads.}, number = {2}, urldate = {2016-01-21}, journal = {Journal of Biomechanical Engineering}, author = {Cowin, S. C. and Moss-Salentijn, L. and Moss, M. L.}, month = may, year = {1991}, keywords = {Chemomechanical transduction}, pages = {191--197}, file = {Cowin et al (1991) - Candidates for the Mechanosensory System in Bone.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6AFG3T62\\Cowin et al (1991) - Candidates for the Mechanosensory System in Bone.pdf:application/pdf} } @inproceedings{zadpoor_bond_2005, title = {A {Bond} {Graph} {Approach} to the {Modeling} of {Fluid}-{Solid} {Interaction} in {Cardiovascuular} {System}'s {Pulsatile} {Flow}}, doi = {10.1109/IEMBS.2005.1616930}, abstract = {A bond graph model of entire cardiovascular system is developed in this paper. Although relying on the concepts of previously developed lumped-parameter models, this new model benefits from some advantages of general system theory which allows the modeler to include as many details as necessary. Specifically, inclusion of pace making mechanism has become much easier. The pace making mechanism is not, however, included in this stage of model development. Modular sources of effort are, instead, predicted in the model to generate synthetic signals close to what occurs in reality. The model is simulated and results of simulation are compared with widely available data of normal cardiovascular system's pressure-flow performance. It has been shown that they are of a good agreement and the model could successfully simulate performance of the human cardiovascular system}, booktitle = {Engineering in {Medicine} and {Biology} {Society}, 2005. {IEEE}-{EMBS} 2005. 27th {Annual} {International} {Conference} of the}, author = {Zadpoor, A.A. and Arshi, A.R. and Nikooyan, A.A.}, month = jan, year = {2005}, keywords = {Biological system modeling, Biomedical Engineering, bond graph model, bond graphs, Bonding, Cardiology, cardiovascular system, cardiovascular system pulsatile flow, fluid-solid interaction, general system theory, haemodynamics, lumped-parameter models, pace making mechanism, physiological models, pressure-flow performance, pulsatile flow}, pages = {2319--2322}, file = {IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VHGKSAWC\\abs_all.html:text/html;Zadpoor et al (2005) - A Bond Graph Approach to the Modeling of Fluid-Solid Interaction in.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6H262C7V\\Zadpoor et al (2005) - A Bond Graph Approach to the Modeling of Fluid-Solid Interaction in.pdf:application/pdf} } @article{ishijima_simultaneous_1998, title = {Simultaneous {Observation} of {Individual} {ATPase} and {Mechanical} {Events} by a {Single} {Myosin} {Molecule} during {Interaction} with {Actin}}, volume = {92}, issn = {0092-8674}, url = {http://www.sciencedirect.com/science/article/pii/S0092867400809113}, doi = {10.1016/S0092-8674(00)80911-3}, abstract = {We have developed a technique that allows mechanical and ligand-binding events in a single myosin molecule to be monitored simultaneously. We describe how steps in the ATPase reaction are temporally related to mechanical events at the single molecule level. The results show that the force generation does not always coincide with the release of bound nucleotide, presumably ADP. Instead the myosin head produces force several hundreds of milliseconds after bound nucleotide is released. This finding does not support the widely accepted view that force generation is directly coupled to the release of bound ligands. It suggests that myosin has a hysteresis or memory state, which stores chemical energy from ATP hydrolysis.}, number = {2}, urldate = {2016-01-24}, journal = {Cell}, author = {Ishijima, Akihiko and Kojima, Hiroaki and Funatsu, Takashi and Tokunaga, Makio and Higuchi, Hideo and Tanaka, Hiroto and Yanagida, Toshio}, month = jan, year = {1998}, keywords = {Actin-myosin}, pages = {161--171}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3AVJPAXV\\S0092867400809113.html:text/html} } @article{luo_mechanisms_2013, title = {Mechanisms of {Altered} {Ca}2+ {Handling} in {Heart} {Failure}}, volume = {113}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/113/6/690}, doi = {10.1161/CIRCRESAHA.113.301651}, abstract = {Ca2+ plays a crucial role in connecting membrane excitability with contraction in myocardium. The hallmark features of heart failure are mechanical dysfunction and arrhythmias; defective intracellular Ca2+ homeostasis is a central cause of contractile dysfunction and arrhythmias in failing myocardium. Defective Ca2+ homeostasis in heart failure can result from pathological alteration in the expression and activity of an increasingly understood collection of Ca2+ homeostatic and structural proteins, ion channels, and enzymes. This review focuses on the molecular mechanisms of defective Ca2+ cycling in heart failure and considers how fundamental understanding of these pathways may translate into novel and innovative therapies.}, language = {en}, number = {6}, urldate = {2016-01-27}, journal = {Circulation Research}, author = {Luo, Min and Anderson, Mark E.}, month = aug, year = {2013}, pmid = {23989713}, keywords = {calcium, CaMKII, excitation-contraction coupling, heart failure, mitochondria, SERCA}, pages = {690--708}, file = {Luo_Anderson (2013) - Mechanisms of Altered Ca2+ Handling in Heart Failure.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D5W3Z48A\\Luo_Anderson (2013) - Mechanisms of Altered Ca2+ Handling in Heart Failure.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\79URBSFE\\690.html:text/html} } @article{geeves_dynamics_1991, title = {The dynamics of actin and myosin association and the crossbridge model of muscle contraction}, volume = {274}, copyright = {© 1991 The Biochemical Society, London}, issn = {0264-6021, 1470-8728}, url = {http://www.biochemj.org.ezp.lib.unimelb.edu.au/content/274/1/1}, doi = {10.1042/bj2740001}, language = {en}, number = {1}, urldate = {2016-01-24}, journal = {Biochemical Journal}, author = {Geeves, M. A.}, month = feb, year = {1991}, pmid = {1825780}, keywords = {Actin-myosin}, pages = {1--14}, file = {Geeves (1991) - The dynamics of actin and myosin association and the crossbridge model of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\635QM3WK\\Geeves (1991) - The dynamics of actin and myosin association and the crossbridge model of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PPPBVGDX\\1.html:text/html} } @article{morris_mechanosensitive_1990, title = {Mechanosensitive ion channels}, volume = {113}, issn = {0022-2631, 1432-1424}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF01872883}, doi = {10.1007/BF01872883}, language = {en}, number = {2}, urldate = {2016-01-24}, journal = {The Journal of Membrane Biology}, author = {Morris, Catherine E.}, month = feb, year = {1990}, keywords = {Biochemistry, general, Chemomechanical transduction, Human Physiology, ion channel, mechanotransduction, single channel recording, stretch-sensitive}, pages = {93--107}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UTEBER9P\\10.html:text/html} } @article{martinac_mechanosensitive_2004, title = {Mechanosensitive ion channels: molecules of mechanotransduction}, volume = {117}, copyright = {© The Company of Biologists Limited 2004}, issn = {0021-9533, 1477-9137}, shorttitle = {Mechanosensitive ion channels}, url = {http://jcs.biologists.org/content/117/12/2449}, doi = {10.1242/jcs.01232}, language = {en}, number = {12}, urldate = {2016-01-24}, journal = {Journal of Cell Science}, author = {Martinac, Boris}, month = may, year = {2004}, pmid = {15159450}, keywords = {Archaea, Bacteria, Chemomechanical transduction, ion channels, Mechanosensitivity, Osmoregulation, Patch clamp}, pages = {2449--2460}, file = {Martinac (2004) - Mechanosensitive ion channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U4T7EMFW\\Martinac (2004) - Mechanosensitive ion channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C4RPJ47Z\\2449.html:text/html} } @article{stossel_filamins_2001, title = {Filamins as integrators of cell mechanics and signalling}, volume = {2}, copyright = {© 2001 Nature Publishing Group}, issn = {1471-0072}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrm/journal/v2/n2/abs/nrm0201_138a.html}, doi = {10.1038/35052082}, abstract = {Filamins are large actin-binding proteins that stabilize delicate three-dimensional actin webs and link them to cellular membranes. They integrate cellular architectural and signalling functions and are essential for fetal development and cell locomotion. Here, we describe the history, structure and function of this group of proteins.}, language = {en}, number = {2}, urldate = {2016-01-24}, journal = {Nature Reviews Molecular Cell Biology}, author = {Stossel, Thomas P. and Condeelis, John and Cooley, Lynn and Hartwig, John H. and Noegel, Angelika and Schleicher, Michael and Shapiro, Sandor S.}, month = feb, year = {2001}, keywords = {Chemomechanical transduction}, pages = {138--145}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UFDFUGCA\\nrm0201_138a.html:text/html;Stossel et al (2001) - Filamins as integrators of cell mechanics and signalling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XAEB8DFE\\Stossel et al (2001) - Filamins as integrators of cell mechanics and signalling.pdf:application/pdf} } @article{karsenti_modelling_2006, title = {Modelling microtubule patterns}, volume = {8}, copyright = {© 2006 Nature Publishing Group}, issn = {1465-7392}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/ncb/journal/v8/n11/abs/ncb1498.html}, doi = {10.1038/ncb1498}, abstract = {The cellular cytoskeleton is well studied in terms of its biological and physical properties, making it an attractive subject for systems approaches. Here, we describe the experimental and theoretical strategies used to study the collective behaviour of microtubules and motors. We illustrate how this led to the beginning of an understanding of dynamic cellular patterns that have precise functions.}, language = {en}, number = {11}, urldate = {2016-01-24}, journal = {Nature Cell Biology}, author = {Karsenti, Eric and Nédélec, François and Surrey, Thomas}, month = nov, year = {2006}, keywords = {molecular motors}, pages = {1204--1211}, file = {Karsenti et al (2006) - Modelling microtubule patterns.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FAPEMNQK\\Karsenti et al (2006) - Modelling microtubule patterns.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\J5HMU6FH\\ncb1498.html:text/html} } @article{peskin_coordinated_1995, title = {Coordinated hydrolysis explains the mechanical behavior of kinesin.}, volume = {68}, issn = {0006-3495}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1281917/}, abstract = {The two-headed motor protein kinesin hydrolyzes nucleotide to move unidirectionally along its microtubule track at speeds up to 1000 nm/s (Saxton et al., 1988) and develops forces in excess of 5 pN (Hunt et al., 1994; Svoboda et al., 1994a). Individual kinesin molecules have been studied recently in vitro, and their behavior has been characterized in terms of force-velocity curves and variance measurements (Svoboda and Block, 1994a; Svoboda et al., 1994b). We present a model for force generation in kinesin in which the ATP hydrolysis reactions are coordinated with the relative positions of the two heads. The model explains the experimental data and permits us to study the relative roles of Brownian motion and elastic deformation in the motor mechanism of kinesin.}, number = {4 Suppl}, urldate = {2016-01-25}, journal = {Biophysical Journal}, author = {Peskin, C S and Oster, G}, month = apr, year = {1995}, pmid = {7787069}, pmcid = {PMC1281917}, keywords = {molecular motors}, pages = {202S--211S}, file = {Peskin_Oster (1995) - Coordinated hydrolysis explains the mechanical behavior of kinesin.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NMWGABRX\\Peskin_Oster (1995) - Coordinated hydrolysis explains the mechanical behavior of kinesin.pdf:application/pdf} } @article{thomas_kinesin:_2002, title = {Kinesin: a molecular motor with a spring in its step}, volume = {269}, issn = {0962-8452, 1471-2954}, shorttitle = {Kinesin}, url = {http://rspb.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/269/1507/2363}, doi = {10.1098/rspb.2002.2117}, abstract = {A key step in the processive motion of two–headed kinesin along a microtubule is the ‘docking’ of the neck linker that joins each kinesin head to the motor's dimerized coiled–coil neck. This process is similar to the folding of a protein β–hairpin, which starts in a highly mobile unfolded state that has significant entropic elasticity and finishes in a more rigid folded state. We therefore suggest that neck–linker docking is mechanically equivalent to the thermally activated shortening of a spring that has been stretched by an applied load. This critical tension–dependent step utilizes Brownian motion and it immediately follows the binding of ATP, the hydrolysis of which provides the free energy that drives the kinesin cycle. A simple three–state model incorporating neck–linker docking can account quantitatively for both the kinesin force–velocity relation and the unusual tension–dependence of its Michaelis constant. However, we find that the observed randomness of the kinesin motor requires a more detailed four–state model. Monte Carlo simulations of single–molecule stepping with this model illustrate the possibility of sub–8 nm steps, the size of which is predicted to vary linearly with the applied load.}, language = {en}, number = {1507}, urldate = {2016-01-25}, journal = {Proceedings of the Royal Society of London B: Biological Sciences}, author = {Thomas, Neil and Imafuku, Yasuhiro and Kamiya, Tsutomu and Tawada, Katsuhisa}, month = nov, year = {2002}, pmid = {12495505}, keywords = {molecular motors}, pages = {2363--2371}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KAVS2IRD\\2363.html:text/html;Thomas et al (2002) - Kinesin.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WS3UT3BV\\Thomas et al (2002) - Kinesin.pdf:application/pdf} } @article{julicher_modeling_1997, title = {Modeling molecular motors}, volume = {69}, url = {http://link.aps.org/doi/10.1103/RevModPhys.69.1269}, doi = {10.1103/RevModPhys.69.1269}, abstract = {The authors present general considerations and simple models for the operation of isothermal motors at small scales, in asymmetric environments. Their work is inspired by recent observations on the behavior of molecular motors in the biological realm, where chemical energy is converted into mechanical energy. A generic Onsager-like description of the linear (close to equilibrium) regime is presented, which exhibits structural differences from the usual Carnot engines. Turning to more explicit models for a single motor, the authors show the importance of the time scales involved and of the spatial dependence of the motor’s chemical activity. Considering the situation in which a large collection of such motors operates together. The authors exhibit new features among which are dynamical phase transitions formally similar to paramagnetic-ferromagnetic and liquid-vapor transitions.}, number = {4}, urldate = {2016-01-25}, journal = {Reviews of Modern Physics}, author = {Jülicher, Frank and Ajdari, Armand and Prost, Jacques}, month = oct, year = {1997}, keywords = {molecular motors}, pages = {1269--1282}, file = {APS Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\44WD5G82\\RevModPhys.69.html:text/html;Jülicher et al (1997) - Modeling molecular motors.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UV6N5IT9\\Jülicher et al (1997) - Modeling molecular motors.pdf:application/pdf} } @article{astumian_role_2000, title = {The role of thermal activation in motion and force generation by molecular motors}, volume = {355}, issn = {0962-8436, 1471-2970}, url = {http://rstb.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/355/1396/511}, doi = {10.1098/rstb.2000.0592}, abstract = {The currently accepted mechanism for ATP–driven motion of kinesin is called the hand–over–hand model, where some chemical transition during the ATP hydrolysis cycle stretches a spring, and motion and force production result from the subsequent relaxation. It is essential in this mechanism for the moving head of kinesin to dissociate, while the other head remains firmly attached to the microtubule. Here we propose an alternative Brownian motor model where the action of ATP modulates the interaction potential between kinesin and the microtubule rather than a spring internal to the kinesin molecule alone. In this model neither head need dissociate (which predicts that under some circumstances a single–headed kinesin can display processive motion) and the transitions by which the motor moves are best described as thermally activated steps. This model is consistent with a wide range of experimental data on the force–velocity curves, the one ATP to one–step stoichiometry observed at small load, and the stochastic properties of the stepping.}, language = {en}, number = {1396}, urldate = {2016-01-25}, journal = {Philosophical Transactions of the Royal Society of London B: Biological Sciences}, author = {Astumian, R. Dean}, month = apr, year = {2000}, pmid = {10836504}, keywords = {molecular motors}, pages = {511--522}, file = {Astumian (2000) - The role of thermal activation in motion and force generation by molecular.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IJGTPBNN\\Astumian (2000) - The role of thermal activation in motion and force generation by molecular.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R4D8DEGV\\511.html:text/html} } @article{coutu_genetic_2005, title = {Genetic manipulation of calcium-handling proteins in cardiac myocytes. {I}. {Experimental} studies}, volume = {288}, copyright = {Copyright © 2005 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/288/2/H601}, doi = {10.1152/ajpheart.00424.2004}, abstract = {Two genetic experimental approaches, de novo expression of parvalbumin (Parv) and overexpression of sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA2a), have been shown to increase relaxation rates in myocardial tissue. However, the relative effect of Parv and SERCA2a on systolic function and on β-adrenergic responsiveness at varied pacing rates is unknown. We used gene transfer in isolated rat adult cardiac myocytes to gain a fuller understanding of Parv/SERCA2a function. As demonstrated previously, when Parv is expressed in elevated concentration ({\textgreater}0.1 mM), the transduced myocytes showed a reduction in sarcomere-shortening amplitude: 129 ± 17, 81 ± 8, and 149 ± 14 nm for control, Parv, and SERCA2a, respectively. At physiological temperature, shortening amplitude responses of Parv and SERCA2a myocytes to the β-adrenergic agonist isoproterenol (Iso) were not statistically different from that of control myocytes. However, in SERCA2a myocytes, in which baseline was slightly elevated and the Iso-stimulated value was slightly lower, the increase in shortening was slightly less than in Parv or control myocytes: 108 ± 14, 169 ± 39, and 34 ± 12\% for control, Parv, and SERCA2a, respectively. In another test set, Parv myocytes had the strongest early postrest potentiation among all groups studied (rest time = 2–10 s), and SERCA2a myocytes were the least sensitive to variations in stimulation rhythm. To replicate the deficient Ca2+ removal observed in heart failure, we used 150 nM thapsigargin. Under these conditions, control myocytes exhibited slowed relaxation, whereas Parv myocytes retained their rapid kinetics, showing that Parv is still able to control relaxation, even when SERCA2a function is impaired.}, language = {en}, number = {2}, urldate = {2016-01-27}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Coutu, Pierre and Metzger, Joseph M.}, month = feb, year = {2005}, pmid = {15331372}, keywords = {SERCA}, pages = {H601--H612}, file = {Coutu_Metzger (2005) - Genetic manipulation of calcium-handling proteins in cardiac myocytes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MPQBF8UX\\Coutu_Metzger (2005) - Genetic manipulation of calcium-handling proteins in cardiac myocytes.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HUM4457M\\H601.html:text/html} } @article{lervik_thermodynamic_2012, title = {On the {Thermodynamic} {Efficiency} of {Ca}2+-{ATPase} {Molecular} {Machines}}, volume = {103}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349512009253}, doi = {10.1016/j.bpj.2012.07.057}, abstract = {Experimental studies have shown that the activity of the reconstituted molecular pump Ca2+-ATPase strongly depends on the thickness of the supporting bilayer. It is thus expected that the bilayer structure will have an impact on the thermodynamic efficiency of this nanomachine. Here, we introduce a nonequilibrium-thermodynamics theoretical approach to estimate the thermodynamic efficiency of the Ca2+-ATPase from analysis of available experimental data about ATP hydrolysis and Ca2+ transport. We find that the entropy production, i.e., the heat released to the surroundings under working conditions, is approximately constant for bilayers containing phospholipids with hydrocarbon chains of 18–22 carbon atoms. Our estimates for the heat released during the pump operation agree with results obtained from separate calorimetric experiments on the Ca2+-ATPase derived from sarcoplasmic reticulum. We show that the thermodynamic efficiency of the reconstituted Ca2+-ATPase reaches a maximum for bilayer thicknesses corresponding to maximum activity. Surprisingly, the estimated thermodynamic efficiency is very low, ∼12\%. We discuss the significance of this result as representative of the efficiency of other nanomachines, and we address the influence of the experimental set-up on such a low efficiency. Overall, our approach provides a general route to estimate thermodynamic efficiencies and heat dissipation in experimental studies of nanomachines.}, number = {6}, urldate = {2016-01-27}, journal = {Biophysical Journal}, author = {Lervik, Anders and Bresme, Fernando and Kjelstrup, Signe and Rubí, J. Miguel}, month = sep, year = {2012}, keywords = {SERCA}, pages = {1218--1226}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WFQMV5J9\\S0006349512009253.html:text/html} } @article{hill_theoretical_1976, title = {Theoretical formalism for the sliding filament model of contraction of striated muscle part {II}}, volume = {29}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/0079610776900213}, doi = {10.1016/0079-6107(76)90021-3}, urldate = {2016-01-28}, journal = {Progress in Biophysics and Molecular Biology}, author = {Hill, Terrell L.}, month = jan, year = {1976}, keywords = {Actin-myosin}, pages = {105--159}, file = {Hill (1976) - Theoretical formalism for the sliding filament model of contraction of striated.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W7U4422N\\Hill (1976) - Theoretical formalism for the sliding filament model of contraction of striated.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7UPDXNGD\\0079610776900213.html:text/html} } @article{worden_cesa_2015, title = {{CESA} {TRAFFICKING} {INHIBITOR} {Inhibits} {Cellulose} {Deposition} and {Interferes} with the {Trafficking} of {Cellulose} {Synthase} {Complexes} and {Their} {Associated} {Proteins} {KORRIGAN}1 and {POM}2/{CELLULOSE} {SYNTHASE} {INTERACTIVE} {PROTEIN}1}, volume = {167}, issn = {, 1532-2548}, url = {http://www.plantphysiol.org/content/167/2/381}, doi = {10.1104/pp.114.249003}, abstract = {Cellulose synthase complexes (CSCs) at the plasma membrane (PM) are aligned with cortical microtubules (MTs) and direct the biosynthesis of cellulose. The mechanism of the interaction between CSCs and MTs, and the cellular determinants that control the delivery of CSCs at the PM, are not yet well understood. We identified a unique small molecule, CESA TRAFFICKING INHIBITOR (CESTRIN), which reduces cellulose content and alters the anisotropic growth of Arabidopsis (Arabidopsis thaliana) hypocotyls. We monitored the distribution and mobility of fluorescently labeled cellulose synthases (CESAs) in live Arabidopsis cells under chemical exposure to characterize their subcellular effects. CESTRIN reduces the velocity of PM CSCs and causes their accumulation in the cell cortex. The CSC-associated proteins KORRIGAN1 (KOR1) and POM2/CELLULOSE SYNTHASE INTERACTIVE PROTEIN1 (CSI1) were differentially affected by CESTRIN treatment, indicating different forms of association with the PM CSCs. KOR1 accumulated in bodies similar to CESA; however, POM2/CSI1 dissociated into the cytoplasm. In addition, MT stability was altered without direct inhibition of MT polymerization, suggesting a feedback mechanism caused by cellulose interference. The selectivity of CESTRIN was assessed using a variety of subcellular markers for which no morphological effect was observed. The association of CESAs with vesicles decorated by the trans-Golgi network-localized protein SYNTAXIN OF PLANTS61 (SYP61) was increased under CESTRIN treatment, implicating SYP61 compartments in CESA trafficking. The properties of CESTRIN compared with known CESA inhibitors afford unique avenues to study and understand the mechanism under which PM-associated CSCs are maintained and interact with MTs and to dissect their trafficking routes in etiolated hypocotyls.}, language = {en}, number = {2}, urldate = {2016-01-28}, journal = {Plant Physiology}, author = {Worden, Natasha and Wilkop, Thomas E. and Esteve, Victor Esteva and Jeannotte, Richard and Lathe, Rahul and Vernhettes, Samantha and Weimer, Bart and Hicks, Glenn and Alonso, Jose and Labavitch, John and Persson, Staffan and Ehrhardt, David and Drakakaki, Georgia}, month = feb, year = {2015}, pmid = {25535279}, keywords = {Plant biology}, pages = {381--393}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QSHZDU9J\\381.html:text/html;Worden et al (2015) - CESA TRAFFICKING INHIBITOR Inhibits Cellulose Deposition and Interferes with.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7FEP3ADT\\Worden et al (2015) - CESA TRAFFICKING INHIBITOR Inhibits Cellulose Deposition and Interferes with.pdf:application/pdf} } @article{schneider_connecting_2015, title = {Connecting two arrays: the emerging role of actin-microtubule cross-linking motor proteins}, shorttitle = {Connecting two arrays}, url = {http://journal.frontiersin.org/article/10.3389/fpls.2015.00415/abstract}, doi = {10.3389/fpls.2015.00415}, abstract = {The cytoskeleton of plant cells, consisting of actin filaments (AFs) and microtubules (MTs), is a central structure for various intracellular processes, such as cell division, isotropic and polar growth, vesicle transport, cell shape, and morphogenesis. Pharmaceutical and genetic studies have provided indications for interdependent cross-talk between the cytoskeletal components. Recent live-cell imaging studies have cemented this notion, in particular when the cytoskeleton rearranges. However, the proteins that directly mediate this cross-talk have remained largely elusive. Recent data indicate that certain proteins can interact with both cytoskeletal arrays at the same time, and hence connecting them. In this review, we summarize the recent literature of the AF- and MT-interactors, mainly focusing on a plant-specific mediator of cytoskeletal cross-talk: the calponin homology (CH) domain-containing kinesin-14 motor proteins (KCHs).}, urldate = {2016-01-28}, journal = {Plant Cell Biology}, author = {Schneider, René and Persson, Staffan}, year = {2015}, keywords = {actin filaments, calponin homology domain, Dynein, kinesin-14, microtubules, Plant biology}, pages = {415}, file = {Schneider_Persson (2015) - Connecting two arrays.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DTCT9PS6\\Schneider_Persson (2015) - Connecting two arrays.pdf:application/pdf} } @article{luo_v-atpase_2015, title = {V-{ATPase} activity in the {TGN}/{EE} is required for exocytosis and recycling in {Arabidopsis}}, volume = {1}, issn = {2055-026X, 2055-0278}, url = {http://www.nature.com/articles/nplants201594}, doi = {10.1038/nplants.2015.94}, number = {7}, urldate = {2016-01-28}, journal = {Nature Plants}, author = {Luo, Yu and Scholl, Stefan and Doering, Anett and Zhang, Yi and Irani, Niloufer G. and Di Rubbo, Simone and Neumetzler, Lutz and Krishnamoorthy, Praveen and Van Houtte, Isabelle and Mylle, Evelien and Bischoff, Volker and Vernhettes, Samantha and Winne, Johan and Friml, Jiří and Stierhof, York-Dieter and Schumacher, Karin and Persson, Staffan and Russinova, Eugenia}, month = jul, year = {2015}, keywords = {Plant biology}, pages = {15094}, file = {Luo et al (2015) - V-ATPase activity in the TGN-EE is required for exocytosis and recycling in.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KPMH4ST6\\Luo et al (2015) - V-ATPase activity in the TGN-EE is required for exocytosis and recycling in.pdf:application/pdf} } @article{liu_connection_2015, title = {The connection of cytoskeletal network with plasma membrane and the cell wall}, volume = {57}, copyright = {© 2015 The Authors. Journal of Integrative Plant Biology published by Wiley Publishing Asia Pty Ltd on behalf of Institute of Botany, The Chinese Academy of Sciences., This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.}, issn = {1744-7909}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/jipb.12342/abstract}, doi = {10.1111/jipb.12342}, abstract = {The cell wall provides external support of the plant cells, while the cytoskeletons including the microtubules and the actin filaments constitute an internal framework. The cytoskeletons contribute to the cell wall biosynthesis by spatially and temporarily regulating the transportation and deposition of cell wall components. This tight control is achieved by the dynamic behavior of the cytoskeletons, but also through the tethering of these structures to the plasma membrane. This tethering may also extend beyond the plasma membrane and impact on the cell wall, possibly in the form of a feedback loop. In this review, we discuss the linking components between the cytoskeletons and the plasma membrane, and/or the cell wall. We also discuss the prospective roles of these components in cell wall biosynthesis and modifications, and aim to provide a platform for further studies in this field.}, language = {en}, number = {4}, urldate = {2016-01-28}, journal = {Journal of Integrative Plant Biology}, author = {Liu, Zengyu and Persson, Staffan and Zhang, Yi}, month = apr, year = {2015}, keywords = {cytoskeleton, Plant biology, plant cell wall, plasma membrane}, pages = {330--340}, file = {Liu et al (2015) - The connection of cytoskeletal network with plasma membrane and the cell wall.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3C7G7MJB\\Liu et al (2015) - The connection of cytoskeletal network with plasma membrane and the cell wall.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NJVE5JF6\\abstract.html:text/html} } @article{breuer_quantitative_2014, title = {Quantitative analyses of the plant cytoskeleton reveal underlying organizational principles}, volume = {11}, copyright = {© 2014 The Author(s) Published by the Royal Society. All rights reserved.}, issn = {1742-5689, 1742-5662}, url = {http://rsif.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/11/97/20140362}, doi = {10.1098/rsif.2014.0362}, abstract = {The actin and microtubule (MT) cytoskeletons are vital structures for cell growth and development across all species. While individual molecular mechanisms underpinning actin and MT dynamics have been intensively studied, principles that govern the cytoskeleton organization remain largely unexplored. Here, we captured biologically relevant characteristics of the plant cytoskeleton through a network-driven imaging-based approach allowing us to quantitatively assess dynamic features of the cytoskeleton. By introducing suitable null models, we demonstrate that the plant cytoskeletal networks exhibit properties required for efficient transport, namely, short average path lengths and high robustness. We further show that these advantageous features are maintained during temporal cytoskeletal rearrangements. Interestingly, man-made transportation networks exhibit similar properties, suggesting general laws of network organization supporting diverse transport processes. The proposed network-driven analysis can be readily used to identify organizational principles of cytoskeletons in other organisms.}, language = {en}, number = {97}, urldate = {2016-02-01}, journal = {Journal of The Royal Society Interface}, author = {Breuer, David and Ivakov, Alexander and Sampathkumar, Arun and Hollandt, Florian and Persson, Staffan and Nikoloski, Zoran}, month = aug, year = {2014}, pmid = {24920110}, keywords = {Plant biology}, pages = {20140362}, file = {Breuer et al (2014) - Quantitative analyses of the plant cytoskeleton reveal underlying.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KXCDK5PP\\Breuer et al (2014) - Quantitative analyses of the plant cytoskeleton reveal underlying.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W7P8M4Z5\\20140362.html:text/html} } @article{mcfarlane_cell_2014, title = {The {Cell} {Biology} of {Cellulose} {Synthesis}}, volume = {65}, url = {http://dx.doi.org/10.1146/annurev-arplant-050213-040240}, doi = {10.1146/annurev-arplant-050213-040240}, abstract = {Plant stature and development are governed by cell proliferation and directed cell growth. These parameters are determined largely by cell wall characteristics. Cellulose microfibrils, composed of hydrogen-bonded β-1,4 glucans, are key components for anisotropic growth in plants. Cellulose is synthesized by plasma membrane–localized cellulose synthase complexes. In higher plants, these complexes are assembled into hexameric rosettes in intracellular compartments and secreted to the plasma membrane. Here, the complexes typically track along cortical microtubules, which may guide cellulose synthesis, until the complexes are inactivated and/or internalized. Determining the regulatory aspects that control the behavior of cellulose synthase complexes is vital to understanding directed cell and plant growth and to tailoring cell wall content for industrial products, including paper, textiles, and fuel. In this review, we summarize and discuss cellulose synthesis and regulatory aspects of the cellulose synthase complex, focusing on Arabidopsis thaliana.}, number = {1}, urldate = {2016-02-01}, journal = {Annual Review of Plant Biology}, author = {McFarlane, Heather E. and Döring, Anett and Persson, Staffan}, year = {2014}, pmid = {24579997}, keywords = {Arabidopsis thaliana, cell wall, extracellular matrix, Plant biology, plant growth and development, secretion}, pages = {69--94}, file = {McFarlane et al (2014) - The Cell Biology of Cellulose Synthesis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RAGPI7AQ\\McFarlane et al (2014) - The Cell Biology of Cellulose Synthesis.pdf:application/pdf} } @article{block_fifty_1996, title = {Fifty {Ways} to {Love} {Your} {Lever}: {Myosin} {Motors}}, volume = {87}, issn = {0092-8674}, shorttitle = {Fifty {Ways} to {Love} {Your} {Lever}}, url = {http://www.sciencedirect.com/science/article/pii/S009286740081332X}, doi = {10.1016/S0092-8674(00)81332-X}, number = {2}, urldate = {2016-02-02}, journal = {Cell}, author = {Block, Steven M}, month = oct, year = {1996}, keywords = {molecular motors}, pages = {151--157}, file = {Block (1996) - Fifty Ways to Love Your Lever.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TNIR3T6U\\Block (1996) - Fifty Ways to Love Your Lever.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NINZAG5V\\S009286740081332X.html:text/html} } @article{bringmann_cracking_2012, title = {Cracking the elusive alignment hypothesis: the microtubule–cellulose synthase nexus unraveled}, volume = {17}, issn = {1360-1385}, shorttitle = {Cracking the elusive alignment hypothesis}, url = {http://www.sciencedirect.com/science/article/pii/S136013851200129X}, doi = {10.1016/j.tplants.2012.06.003}, abstract = {Directed plant cell growth is governed by deposition and alterations of cell wall components under turgor pressure. A key regulatory element of anisotropic growth, and hence cell shape, is the directional deposition of cellulose microfibrils. The microfibrils are synthesized by plasma membrane-located cellulose synthase complexes that co-align with and move along cortical microtubules. That the parallel relation between cortical microtubules and extracellular microfibrils is causal has been named the alignment hypothesis. Three recent studies revealed that the previously identified pom2 mutant codes for a large cellulose synthases interacting (CSI1) protein which also binds cortical microtubules. This review summarizes these findings, provides structure–function models and discusses the inferred mechanisms in the context of plant growth.}, number = {11}, urldate = {2016-02-03}, journal = {Trends in Plant Science}, author = {Bringmann, Martin and Landrein, Benoit and Schudoma, Christian and Hamant, Olivier and Hauser, Marie-Theres and Persson, Staffan}, month = nov, year = {2012}, keywords = {Plant biology}, pages = {666--674}, file = {Bringmann et al (2012) - Cracking the elusive alignment hypothesis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CJ8VD5HH\\Bringmann et al (2012) - Cracking the elusive alignment hypothesis.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C6HMXSAK\\S136013851200129X.html:text/html} } @article{meyhofer_force_1995, title = {The force generated by a single kinesin molecule against an elastic load.}, volume = {92}, issn = {0027-8424, 1091-6490}, url = {http://www.pnas.org/content/92/2/574}, doi = {10.1073/pnas.92.2.574}, abstract = {To probe the mechanism by which the motor protein kinesin moves along microtubules, we have developed a highly sensitive technique for measuring the force exerted by a single motor molecule. In this technique, one end of a microtubule is attached to the tip of a flexible glass fiber of calibrated stiffness. The other end of the microtubule makes contact with a surface sparsely coated with kinesin. By imaging the tip of the glass fiber on a photodiode detector, displacement of the microtubule by kinesin through as little as 1 nm can be detected and forces as small as 1 pN resolved. Using this force-fiber apparatus we have characterized the mechanical output of this molecular motor. The speed at which a molecule of kinesin moved along the surface of a microtubule decreased linearly as the elastic force was increased. The force required to stop a single kinesin molecule was 5.4 +/- 1.0 pN (mean +/- SD; n = 16), independent of the stiffness of the fiber, the damping from the fluid, and whether the ATP concentration was high or low.}, language = {en}, number = {2}, urldate = {2016-02-04}, journal = {Proceedings of the National Academy of Sciences}, author = {Meyhöfer, E. and Howard, J.}, month = jan, year = {1995}, pmid = {7831332}, pages = {574--578}, file = {Meyhöfer_Howard (1995) - The force generated by a single kinesin molecule against an elastic load.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZDDNRJTI\\Meyhöfer_Howard (1995) - The force generated by a single kinesin molecule against an elastic load.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IVCVBC87\\574.html:text/html} } @article{paredez_visualization_2006, title = {Visualization of {Cellulose} {Synthase} {Demonstrates} {Functional} {Association} with {Microtubules}}, volume = {312}, copyright = {American Association for the Advancement of Science}, issn = {0036-8075, 1095-9203}, url = {http://science.sciencemag.org.ezp.lib.unimelb.edu.au/content/312/5779/1491}, doi = {10.1126/science.1126551}, abstract = {Expression of a functional yellow fluorescent protein fusion to cellulose synthase (CESA) in transgenic Arabidopsis plants allowed the process of cellulose deposition to be visualized in living cells. Spinning disk confocal microscopy revealed that CESA complexes in the plasma membrane moved at constant rates in linear tracks that were aligned and were coincident with cortical microtubules. Within each observed linear track, complex movement was bidirectional. Inhibition of microtubule polymerization changed the fine-scale distribution and pattern of moving CESA complexes in the membrane, indicating a relatively direct mechanism for guidance of cellulose deposition by the cytoskeleton. Cellulose synthase makes and deposits cellulose along plant cell walls as it is carried along microtubules. Cellulose synthase makes and deposits cellulose along plant cell walls as it is carried along microtubules.}, language = {en}, number = {5779}, urldate = {2016-02-03}, journal = {Science}, author = {Paredez, Alexander R. and Somerville, Christopher R. and Ehrhardt, David W.}, month = jun, year = {2006}, pmid = {16627697}, keywords = {Plant biology}, pages = {1491--1495}, file = {Paredez et al (2006) - Visualization of Cellulose Synthase Demonstrates Functional Association with.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZRFWDAEB\\Paredez et al (2006) - Visualization of Cellulose Synthase Demonstrates Functional Association with.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QEWE2V88\\1491.full.html:text/html} } @article{diotallevi_cellulose_2007, title = {The {Cellulose} {Synthase} {Complex}: {A} {Polymerization} {Driven} {Supramolecular} {Motor}}, volume = {92}, issn = {0006-3495}, shorttitle = {The {Cellulose} {Synthase} {Complex}}, url = {http://www.sciencedirect.com/science/article/pii/S000634950771072X}, doi = {10.1529/biophysj.106.099473}, abstract = {We present a biophysical model for the propulsion of the cellulose synthase complex, the motile transmembrane protein complex responsible for the biosynthesis of cellulose microfibrils, the dominant architectural component of the cell walls of higher plants. Our model identifies the polymerization and the crystallization of the cellulose chains as the combined driving forces and elucidates the role of polymer flexibility and membrane elasticity as force transducers. The model is elaborated using both stochastic simulations and a simplified analytical treatment. On the basis of the model and approximate values for the relevant physical constants, we estimate the speed of the cellulose synthase complex to be in the range vp ≈ 10−9–10−8 m/s, consistent with the recently reported experimental value of 5.8 × 10−9 m/s.}, number = {8}, urldate = {2016-02-03}, journal = {Biophysical Journal}, author = {Diotallevi, Fabiana and Mulder, Bela}, month = apr, year = {2007}, keywords = {Plant biology}, pages = {2666--2673}, file = {Diotallevi_Mulder (2007) - The Cellulose Synthase Complex.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XR76GITF\\Diotallevi_Mulder (2007) - The Cellulose Synthase Complex.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8FXRE4GF\\S000634950771072X.html:text/html} } @article{somerville_cellulose_2006, title = {Cellulose {Synthesis} in {Higher} {Plants}}, volume = {22}, url = {http://dx.doi.org/10.1146/annurev.cellbio.22.022206.160206}, doi = {10.1146/annurev.cellbio.22.022206.160206}, abstract = {AbstractCellulose microfibrils play essential roles in the organization of plant cell walls, thereby allowing a growth habit based on turgor. The fibrils are made by 30 nm diameter plasma membrane complexes composed of approximately 36 subunits representing at least three types of related CESA proteins. The complexes assemble in the Golgi, where they are inactive, and move to the plasma membrane, where they become activated. The complexes move through the plasma membrane during cellulose synthesis in directions that coincide with the orientation of microtubules. Recent, simultaneous, live-cell imaging of cellulose synthase and microtubules indicates that the microtubules exert a direct influence on the orientation of cellulose deposition. Genetic studies in Arabidopsis have identified a number of genes that contribute to the overall process of cellulose synthesis, but the role of these proteins is not yet known.}, number = {1}, urldate = {2016-02-08}, journal = {Annual Review of Cell and Developmental Biology}, author = {Somerville, Chris}, year = {2006}, pmid = {16824006}, keywords = {cellulose synthase, cell wall, microtubules, mutant, regulation, transcription}, pages = {53--78}, file = {Somerville (2006) - Cellulose Synthesis in Higher Plants.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EMIMJC62\\Somerville (2006) - Cellulose Synthesis in Higher Plants.pdf:application/pdf} } @article{kawagoe_thermodynamics_2006, title = {Thermodynamics in cellulose biosynthesis: {Entropy}-driven synthesis of cellulose microfibrils}, shorttitle = {Thermodynamics in cellulose biosynthesis}, author = {Kawagoe, Yasushi}, year = {2006}, pages = {106--113}, file = {Kawagoe (2006) - Thermodynamics in cellulose biosynthesis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5W3FHS3K\\Kawagoe (2006) - Thermodynamics in cellulose biosynthesis.pdf:application/pdf;Thermodynamics in cellulose biosynthesis\: Entropy-driven synthesis of cellulose microfibrils (PDF Download Available):C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BTGQV8GA\\236147622_Thermodynamics_in_cellulose_biosynthesis_Entropy-driven_synthesis_of_cellulose_microf.html:text/html} } @article{kumar_plant_2015, series = {In {Memory} of {G}. {Paul} {Bolwell}: {Plant} {Cell} {Wall} {Dynamics}}, title = {Plant cellulose synthesis: {CESA} proteins crossing kingdoms}, volume = {112}, issn = {0031-9422}, shorttitle = {Plant cellulose synthesis}, url = {http://www.sciencedirect.com/science/article/pii/S0031942214002799}, doi = {10.1016/j.phytochem.2014.07.009}, abstract = {Cellulose is a biopolymer of considerable economic importance. It is synthesised by the cellulose synthase complex (CSC) in species ranging from bacteria to higher plants. Enormous progress in our understanding of bacterial cellulose synthesis has come with the recent publication of both the crystal structure and biochemical characterisation of a purified complex able to synthesis cellulose in vitro. A model structure of a plant CESA protein suggests considerable similarity between the bacterial and plant cellulose synthesis. In this review article we will cover current knowledge of how plant CESA proteins synthesise cellulose. In particular the focus will be on the lessons learned from the recent work on the catalytic mechanism and the implications that new data on cellulose structure has for the assembly of CESA proteins into the large complex that synthesis plant cellulose microfibrils.}, urldate = {2016-02-08}, journal = {Phytochemistry}, author = {Kumar, Manoj and Turner, Simon}, month = apr, year = {2015}, keywords = {BcsA structure, Catalytic subunit, Cellulose biosynthesis, Cellulose microfibril, CESA proteins model}, pages = {91--99}, file = {Kumar_Turner (2015) - Plant cellulose synthesis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\557MSIBA\\Kumar_Turner (2015) - Plant cellulose synthesis.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DI4TQN9M\\S0031942214002799.html:text/html} } @article{endler_glycobiology:_2010, title = {Glycobiology: {Cellulose} squeezes through}, volume = {6}, copyright = {© 2010 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, issn = {1552-4450}, shorttitle = {Glycobiology}, url = {http://www.nature.com/nchembio/journal/v6/n12/full/nchembio.480.html}, doi = {10.1038/nchembio.480}, abstract = {The glucose-based polymer cellulose is of great biological and economical importance; however, little is known about how cellulose is synthesized. Now, structural estimates of one of the cellulose-synthesizing subunits in the bacterium Acetobacter xylinum help to explain the extrusion of the newly synthesized glucan chains.}, language = {en}, number = {12}, urldate = {2016-02-08}, journal = {Nature Chemical Biology}, author = {Endler, Anne and Sánchez-Rodríguez, Clara and Persson, Staffan}, month = dec, year = {2010}, keywords = {Bacteria, Biopolymers, Biosynthesis, Glycobiology}, pages = {883--884}, file = {Endler et al (2010) - Glycobiology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TCXU696K\\Endler et al (2010) - Glycobiology.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I2R33BV3\\nchembio.480.html:text/html} } @incollection{saxena_biochemistry_2008, series = {Bioengineering and {Molecular} {Biology} of {Plant} {Pathways}}, title = {Biochemistry and {Molecular} {Biology} of {Cellulose} {Biosynthesis} in {Plants}: {Prospects} for {Genetic} {Engineering}}, volume = {1}, shorttitle = {Biochemistry and {Molecular} {Biology} of {Cellulose} {Biosynthesis} in {Plants}}, url = {http://www.sciencedirect.com/science/article/pii/S1755040807010065}, abstract = {Cellulose is a major component of the plant cell wall, and understanding the mechanism of synthesis of this polysaccharide is a major challenge for plant biologists. Cellulose microfibrils are synthesized and assembled by membrane‐localized protein complexes that are visualized as rosettes by freeze‐fracture electron microscopy. Cellulose synthase is required for cellulose synthesis. So far only this enzyme has been localized to these cellulose‐synthesizing complexes. Although it has not been possible to purify and fully characterize cellulose synthase activity from plants, it has been possible to obtain cellulose synthesis in vitro using membranes and detergent‐solubilized membrane fractions. Cellulose synthase uses uridine 5′‐diphosphate (UDP)‐glucose as a substrate and polymerizes glucose residues into long β‐1,4‐linked glucan chains in a single‐step reaction. Cellulose synthases are encoded by genes belonging to a superfamily, and each plant synthesizes a number of different cellulose synthases. Genetic analysis suggests that each cellulose‐synthesizing complex contains at least three nonredundant cellulose synthases and mutation in any one of these cellulose synthases results in cellulose deficiency. More interestingly, different cellulose synthases perform cellulose synthesis in the primary cell wall and the secondary cell wall. Apart from the cellulose synthases, a number of other proteins have been suggested to play a role in cellulose synthesis, but so far their functions are not clearly understood. Genetic manipulation of cellulose synthesis in plants will therefore require not only a complete understanding of the different cellulose synthases but also other proteins that regulate the temporal and spatial synthesis and assembly of this very important polysaccharide.}, urldate = {2016-02-08}, publisher = {Pergamon}, author = {Saxena, Inder M. and Brown Jr., Malcolm R.}, editor = {Biology, BT - Advances in Plant Biochemistry {and} Molecular}, year = {2008}, keywords = {Acetobacter xylinum, Arabidopsis, Cellulose, Cellulose biosynthesis, cellulose synthase, Cellulose synthase‐like, CesA, Cotton, Csl, Genetic manipulations}, pages = {135--160}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9XFAU29W\\S1755040807010065.html:text/html} } @article{hariadi_mechanical_2015, title = {Mechanical coordination in motor ensembles revealed using engineered artificial myosin filaments}, volume = {10}, copyright = {© 2015 Nature Publishing Group}, issn = {1748-3387}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nnano/journal/v10/n8/abs/nnano.2015.132.html}, doi = {10.1038/nnano.2015.132}, abstract = {The sarcomere of muscle is composed of tens of thousands of myosin motors that self-assemble into thick filaments and interact with surrounding actin-based thin filaments in a dense, near-crystalline hexagonal lattice. Together, these actin–myosin interactions enable large-scale movement and force generation, two primary attributes of muscle. Research on isolated fibres has provided considerable insight into the collective properties of muscle, but how actin–myosin interactions are coordinated in an ensemble remains poorly understood. Here, we show that artificial myosin filaments, engineered using a DNA nanotube scaffold, provide precise control over motor number, type and spacing. Using both dimeric myosin V- and myosin VI-labelled nanotubes, we find that neither myosin density nor spacing has a significant effect on the gliding speed of actin filaments. This observation supports a simple model of myosin ensembles as energy reservoirs that buffer individual stochastic events to bring about smooth, continuous motion. Furthermore, gliding speed increases with cross-bridge compliance, but is limited by Brownian effects. As a first step to reconstituting muscle motility, we demonstrate human β-cardiac myosin-driven gliding of actin filaments on DNA nanotubes.}, language = {en}, number = {8}, urldate = {2016-02-09}, journal = {Nature Nanotechnology}, author = {Hariadi, R. F. and Sommese, R. F. and Adhikari, A. S. and Taylor, R. E. and Sutton, S. and Spudich, J. A. and Sivaramakrishnan, S.}, month = aug, year = {2015}, keywords = {DNA nanostructures, Nanostructures}, pages = {696--700}, file = {Hariadi et al (2015) - Mechanical coordination in motor ensembles revealed using engineered artificial.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZSRXG2ZD\\Hariadi et al (2015) - Mechanical coordination in motor ensembles revealed using engineered artificial.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FUHERQMV\\nnano.2015.132.html:text/html} } @article{walcott_mechanical_2012, title = {Mechanical {Coupling} between {Myosin} {Molecules} {Causes} {Differences} between {Ensemble} and {Single}-{Molecule} {Measurements}}, volume = {103}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349512007205}, doi = {10.1016/j.bpj.2012.06.031}, abstract = {In contracting muscle, individual myosin molecules function as part of a large ensemble, hydrolyzing ATP to power the relative sliding of actin filaments. The technological advances that have enabled direct observation and manipulation of single molecules, including recent experiments that have explored myosin’s force-dependent properties, provide detailed insight into the kinetics of myosin’s mechanochemical interaction with actin. However, it has been difficult to reconcile these single-molecule observations with the behavior of myosin in an ensemble. Here, using a combination of simulations and theory, we show that the kinetic mechanism derived from single-molecule experiments describes ensemble behavior; but the connection between single molecule and ensemble is complex. In particular, even in the absence of external force, internal forces generated between myosin molecules in a large ensemble accelerate ADP release and increase how far actin moves during a single myosin attachment. These myosin-induced changes in strong binding lifetime and attachment distance cause measurable properties, such as actin speed in the motility assay, to vary depending on the number of myosin molecules interacting with an actin filament. This ensemble-size effect challenges the simple detachment limited model of motility, because even when motility speed is limited by ADP release, increasing attachment rate can increase motility speed.}, number = {3}, urldate = {2016-02-09}, journal = {Biophysical Journal}, author = {Walcott, Sam and Warshaw, David M. and Debold, Edward P.}, month = aug, year = {2012}, pages = {501--510}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IBMFB8I5\\S0006349512007205.html:text/html;Walcott et al (2012) - Mechanical Coupling between Myosin Molecules Causes Differences between.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6PHPVX33\\Walcott et al (2012) - Mechanical Coupling between Myosin Molecules Causes Differences between.pdf:application/pdf} } @article{wang_salt-related_2015, title = {Salt-{Related} {MYB}1 ({SRM}1) {Coordinates} {Abscisic} {Acid} {Biosynthesis} and {Signaling} {During} {Salt} {Stress} in {Arabidopsis}}, issn = {, 1532-2548}, url = {http://www.plantphysiol.org/content/early/2015/08/04/pp.15.00962}, doi = {10.1104/pp.15.00962}, abstract = {Abiotic stress, such as salinity, cause global yield loss of all major crop plants. Factors and mechanisms that can aid in plant breeding for salt stress tolerance are therefore of great importance for food and feed production. Here, we identified a MYB-like transcription factor, Salt-Related MYB1 (SRM1), that negatively affects Arabidopsis seed germination under saline conditions by regulating the levels of the stress hormone abscisic acid (ABA). Accordingly, several ABA biosynthesis and signaling genes act directly downstream of SRM1, including STO1/NINE-CIS-EPOXYCAROTENOID DIOXYGENASE3 (NCED3), RESPONSIVE TO DESICCATION 26 (RD26) and ANAC019. Furthermore, SRM1 impacts on vegetative growth and leaf shape. We show that SRM1 is an important transcriptional regulator that directly targets ABA biosynthesis and signaling-related genes and therefore may be regarded as an important regulator of ABA mediated salt stress tolerance.}, language = {en}, urldate = {2016-02-15}, journal = {Plant Physiology}, author = {Wang, Ting and Tohge, Takayaki and Ivakov, Alexander A. and Mueller-Roeber, Bernd and Fernie, Alisdair R. and Mutwil, Marek and Schippers, Jos H. M. and Persson, Staffan}, month = aug, year = {2015}, pmid = {26243618}, pages = {pp.00962.2015}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\55QNA3WE\\pp.15.00962.html:text/html;Wang et al (2015) - Salt-Related MYB1 (SRM1) Coordinates Abscisic Acid Biosynthesis and Signaling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IUA3S24N\\Wang et al (2015) - Salt-Related MYB1 (SRM1) Coordinates Abscisic Acid Biosynthesis and Signaling.pdf:application/pdf} } @article{egan_emergent_2015, title = {Emergent {Systems} {Energy} {Laws} for {Predicting} {Myosin} {Ensemble} {Processivity}}, volume = {11}, url = {http://dx.doi.org/10.1371/journal.pcbi.1004177}, doi = {10.1371/journal.pcbi.1004177}, abstract = {Author Summary Complex biological systems consist of many parts that interact in non-obvious ways. In these systems, levels of organization often emerge, as evidenced by cases where cells form tissues, tissues form organs, and organs interact to form complete organisms. We hypothesized that that laws exist that describe system functioning at one level, independently of the configuration at other levels. The hypothesis was tested using simulations of motor protein systems, and demonstrated that patterns in their behavior emerge at a systems level. Results demonstrated a law concerning energy utilization predicts the lifetime of these systems before dissociation, regardless of the components present in the system. These findings reveal organizational laws that simplify complex systems analysis and can facilitate engineering design approaches for bio-based technologies.}, number = {4}, urldate = {2016-02-09}, journal = {PLoS Comput Biol}, author = {Egan, Paul and Moore, Jeffrey and Schunn, Christian and Cagan, Jonathan and LeDuc, Philip}, month = apr, year = {2015}, pages = {e1004177}, file = {Egan et al (2015) - Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XIC4WER7\\Egan et al (2015) - Emergent Systems Energy Laws for Predicting Myosin Ensemble Processivity.pdf:application/pdf} } @article{guerin_coordination_2010, series = {Cell structure and dynamics}, title = {Coordination and collective properties of molecular motors: theory}, volume = {22}, issn = {0955-0674}, shorttitle = {Coordination and collective properties of molecular motors}, url = {http://www.sciencedirect.com/science/article/pii/S0955067409002415}, doi = {10.1016/j.ceb.2009.12.012}, abstract = {Many cellular processes require molecular motors to produce motion and forces. Single molecule experiments have led to a precise description of how a motor works. Under most physiological conditions, however, molecular motors operate in groups. Interactions between motors yield collective behaviors that cannot be explained only from single molecule properties. The aim of this paper is to review the various theoretical descriptions that explain the emergence of collective effects in molecular motor assemblies. These include bidirectional motion, hysteretic behavior, spontaneous oscillations, and self-organization into dynamical structures. We discuss motors acting on the cytoskeleton both in a prescribed geometry such as in muscles or flagella and in the cytoplasm.}, number = {1}, urldate = {2016-02-09}, journal = {Current Opinion in Cell Biology}, author = {Guérin, Thomas and Prost, Jacques and Martin, Pascal and Joanny, Jean-François}, month = feb, year = {2010}, pages = {14--20}, file = {Guérin et al (2010) - Coordination and collective properties of molecular motors.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\39BAKJ7A\\Guérin et al (2010) - Coordination and collective properties of molecular motors.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\X7PZ3BPH\\S0955067409002415.html:text/html} } @article{taylor_cellulose_2008, title = {Cellulose biosynthesis and deposition in higher plants}, volume = {178}, issn = {1469-8137}, url = {http://onlinelibrary.wiley.com/doi/10.1111/j.1469-8137.2008.02385.x/abstract}, doi = {10.1111/j.1469-8137.2008.02385.x}, abstract = {Contents Summary1I.Introduction2II.Structure of cellulose2III.Cellulose synthase2IV.Mutations affecting cellulose synthesis4V.Cellulose synthase complex assembly6VI.Transcriptomic approaches to identify genes involved in cellulose synthesis7VII.Purification of the cellulose synthase complex8VIII.Regulation of cellulose synthesis8IX.Feedback responses to cell wall defects9X.Regulation of orientation of cellulose deposition10XI.Cellulose as a source of renewable energy10XII.Conclusions11Acknowledgements11References11 Summary The plant cell wall is central to plant development. Cellulose is a major component of plant cell walls, and is the world's most abundant biopolymer. Cellulose contains apparently simple linear chains of glucose residues, but these chains aggregate to form immensely strong microfibrils. It is the physical properties of these microfibrils that, when laid down in an organized manner, are responsible for both oriented cell elongation during plant growth and the strength required to maintain an upright growth habit. Despite the importance of cellulose, only recently have we started to unravel details of its synthesis. Mutational analysis has allowed us to identify some of the proteins involved in its synthesis at the plasma membrane, and to define a set of cellulose synthase enzymes essential for cellulose synthesis. These proteins are organized into a very large plasma membrane-localized protein complex. The way in which this protein complex is regulated and directed is central in depositing cellulose microfibrils in the wall in the correct orientation, which is essential for directional cell growth. Recent developments have given us clues as to how cellulose synthesis and deposition is regulated, an understanding of which is essential if we are to manipulate cell wall composition.}, language = {en}, number = {2}, urldate = {2016-02-09}, journal = {New Phytologist}, author = {Taylor, Neil G.}, month = apr, year = {2008}, keywords = {Cellulose, cellulose synthase, cell wall, Microtubule, plant development}, pages = {239--252}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8I6HBUW9\\abstract.html:text/html;Taylor (2008) - Cellulose biosynthesis and deposition in higher plants.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PJXP2EJV\\Taylor (2008) - Cellulose biosynthesis and deposition in higher plants.pdf:application/pdf} } @article{smith_efficiency_2005, title = {The efficiency of muscle contraction}, volume = {88}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/S0079610703001081}, doi = {10.1016/j.pbiomolbio.2003.11.014}, abstract = {When a muscle contracts and shortens against a load, it performs work. The performance of work is fuelled by the expenditure of metabolic energy, more properly quantified as enthalpy (i.e., heat plus work). The ratio of work performed to enthalpy produced provides one measure of efficiency. However, if the primary interest is in the efficiency of the actomyosin cross-bridges, then the metabolic overheads associated with basal metabolism and excitation–contraction coupling, together with those of subsequent metabolic recovery process, must be subtracted from the total heat and work observed. By comparing the cross-bridge work component of the remainder to the Gibbs free energy of hydrolysis of ATP, a measure of thermodynamic efficiency is achieved. We describe and quantify this partitioning process, providing estimates of the efficiencies of selected steps, while discussing the errors that can arise in the process of quantification. The dependence of efficiency on animal species, fibre-type, temperature, and contractile velocity is considered. The effect of contractile velocity on energetics is further examined using a two-state, Huxley-style, mathematical model of cross-bridge cycling that incorporates filament compliance. Simulations suggest only a modest effect of filament compliance on peak efficiency, but progressively larger gains (vis-à-vis the rigid filament case) as contractile velocity approaches Vmax. This effect is attributed primarily to a reduction in the component of energy loss arising from detachment of cross-bridge heads at non-zero strain.}, number = {1}, urldate = {2016-02-16}, journal = {Progress in Biophysics and Molecular Biology}, author = {Smith, Nicholas P. and Barclay, Christopher J. and Loiselle, Denis S.}, month = may, year = {2005}, keywords = {Cross-bridges, Efficiency, energy, Enthalpy, Fibre-type, Species-differences}, pages = {1--58}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V286C7FB\\S0079610703001081.html:text/html;Smith et al (2005) - The efficiency of muscle contraction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\N2PHT28D\\Smith et al (2005) - The efficiency of muscle contraction.pdf:application/pdf} } @article{endler_mechanism_2015, title = {A {Mechanism} for {Sustained} {Cellulose} {Synthesis} during {Salt} {Stress}}, volume = {162}, issn = {0092-8674}, url = {http://www.sciencedirect.com/science/article/pii/S0092867415010429}, doi = {10.1016/j.cell.2015.08.028}, abstract = {Summary Abiotic stress, such as salinity, drought, and cold, causes detrimental yield losses for all major plant crop species. Understanding mechanisms that improve plants’ ability to produce biomass, which largely is constituted by the plant cell wall, is therefore of upmost importance for agricultural activities. Cellulose is a principal component of the cell wall and is synthesized by microtubule-guided cellulose synthase enzymes at the plasma membrane. Here, we identified two components of the cellulose synthase complex, which we call companion of cellulose synthase (CC) proteins. The cytoplasmic tails of these membrane proteins bind to microtubules and promote microtubule dynamics. This activity supports microtubule organization, cellulose synthase localization at the plasma membrane, and renders seedlings less sensitive to stress. Our findings offer a mechanistic model for how two molecular components, the CC proteins, sustain microtubule organization and cellulose synthase localization and thus aid plant biomass production during salt stress. Video Abstract}, number = {6}, urldate = {2016-02-26}, journal = {Cell}, author = {Endler, Anne and Kesten, Christopher and Schneider, René and Zhang, Yi and Ivakov, Alexander and Froehlich, Anja and Funke, Norma and Persson, Staffan}, month = sep, year = {2015}, pages = {1353--1364}, file = {Endler et al (2015) - A Mechanism for Sustained Cellulose Synthesis during Salt Stress.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ICFAGGNB\\Endler et al (2015) - A Mechanism for Sustained Cellulose Synthesis during Salt Stress.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CTUKA3J3\\S0092867415010429.html:text/html} } @article{nickerson_human_2016, title = {The {Human} {Physiome}: how standards, software and innovative service infrastructures are providing the building blocks to make it achievable}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, shorttitle = {The {Human} {Physiome}}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150103}, doi = {10.1098/rsfs.2015.0103}, abstract = {Reconstructing and understanding the Human Physiome virtually is a complex mathematical problem, and a highly demanding computational challenge. Mathematical models spanning from the molecular level through to whole populations of individuals must be integrated, then personalized. This requires interoperability with multiple disparate and geographically separated data sources, and myriad computational software tools. Extracting and producing knowledge from such sources, even when the databases and software are readily available, is a challenging task. Despite the difficulties, researchers must frequently perform these tasks so that available knowledge can be continually integrated into the common framework required to realize the Human Physiome. Software and infrastructures that support the communities that generate these, together with their underlying standards to format, describe and interlink the corresponding data and computer models, are pivotal to the Human Physiome being realized. They provide the foundations for integrating, exchanging and re-using data and models efficiently, and correctly, while also supporting the dissemination of growing knowledge in these forms. In this paper, we explore the standards, software tooling, repositories and infrastructures that support this work, and detail what makes them vital to realizing the Human Physiome.}, language = {en}, number = {2}, urldate = {2016-03-03}, journal = {Interface Focus}, author = {Nickerson, David and Atalag, Koray and Bono, Bernard de and Geiger, Jörg and Goble, Carole and Hollmann, Susanne and Lonien, Joachim and Müller, Wolfgang and Regierer, Babette and Stanford, Natalie J. and Golebiewski, Martin and Hunter, Peter}, month = apr, year = {2016}, pages = {20150103}, file = {Nickerson et al (2016) - The Human Physiome.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C5IXRSQC\\Nickerson et al (2016) - The Human Physiome.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BNNXK34D\\20150103.html:text/html} } @article{robinson_extension_1994, title = {Extension of bond graphs to probability distribution functions}, volume = {331}, issn = {0016-0032}, url = {http://www.sciencedirect.com/science/article/pii/0016003294900817}, doi = {10.1016/0016-0032(94)90081-7}, abstract = {The modeling of a broad class of probability density functions using bond graphs is discussed. The specific class of density functions considered is referred to as phase distribution. Extensive use of these distributions has been made in the area of queuing theory and the modeling of communication systems. Recently, these distributions have been finding wider use in the modeling of reliability, maintainability and availability characteristics of many complex systems. On the other hand, bond graphs have been extremely useful as a deterministic modeling tool for the concurrent, multidisciplinary conceptual design of complex systems. By introducing this extension of bond graph theory it is hoped that a more concerted effort will begin to consider the stochastic nature of system performance during conceptual design.}, number = {1}, urldate = {2016-02-26}, journal = {Journal of the Franklin Institute}, author = {Robinson, David G.}, month = jan, year = {1994}, pages = {101--108}, file = {Robinson (1994) - Extension of bond graphs to probability distribution functions.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JM3GX4FX\\Robinson (1994) - Extension of bond graphs to probability distribution functions.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\Q246DCZI\\0016003294900817.html:text/html} } @article{viceconti_virtual_2016, title = {The {Virtual} {Physiological} {Human}: {Ten} {Years} {After}}, volume = {18}, shorttitle = {The {Virtual} {Physiological} {Human}}, url = {http://www.annualreviews.org/doi/abs/10.1146/annurev-bioeng-110915-114742}, doi = {10.1146/annurev-bioeng-110915-114742}, abstract = {Biomedical research and clinical practice are struggling to cope with the growing complexity that the progress of healthcare involves. The most challenging diseases, those with the largest socioeconomic impact (cardiovascular conditions, musculoskeletal conditions, cancer, metabolic, immunity and neurodegenerative conditions) are all characterised by a complex genotype/phenotype interaction, and in general by a “systemic” nature that the traditional reductionist approach struggle to cope with. In May 2005 a small group of researchers with different backgrounds met in Barcelona to discuss how the vision of computational physiology promoted by the Physiome Project could be translated into the clinical practice. In that meeting the term Virtual Physiological Human was formally proposed. We know a lot about these diseases, but our knowledge is fragmentary as it is associated with molecular and cellular processes on the one hand, and with tissue and organ phenotype changes (related to clinical symptoms of disease conditions) on the other. The problem could be solved if we could capture all these fragments of knowledge into predictive models and then compose them into hypermodels that help us to tame the complexity that such systemic behaviour involves. In 2005 this was simply not possible - the necessary methods and technologies were not available. Now, ten years later, it seems the right time to reflect on the original vision, the results achieved so far, and what remains to be done. Expected final online publication date for the Annual Review of Biomedical Engineering Volume 18 is July 11, 2016. Please see http://www.annualreviews.org/catalog/pubdates.aspx for revised estimates.}, number = {1}, urldate = {2016-03-03}, journal = {Annual Review of Biomedical Engineering}, author = {Viceconti, Marco and Hunter, Peter}, year = {2016}, pages = {null} } @article{tran_regulation_2015, title = {Regulation of cardiac cellular bioenergetics: mechanisms and consequences}, volume = {3}, copyright = {© 2015 The Authors. Physiological Reports published by Wiley Periodicals, Inc. on behalf of the American Physiological Society and The Physiological Society.. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.}, issn = {2051-817X, 2051-817X}, shorttitle = {Regulation of cardiac cellular bioenergetics}, url = {http://physreports.physiology.org.ezp.lib.unimelb.edu.au/content/3/7/e12464}, doi = {10.14814/phy2.12464}, abstract = {The regulation of cardiac cellular bioenergetics is critical for maintaining normal cell function, yet the nature of this regulation is not fully understood. Different mechanisms have been proposed to explain how mitochondrial ATP production is regulated to match changing cellular energy demand while metabolite concentrations are maintained. We have developed an integrated mathematical model of cardiac cellular bioenergetics, electrophysiology, and mechanics to test whether stimulation of the dehydrogenase flux by Ca2+ or Pi, or stimulation of complex III by Pi can increase the rate of mitochondrial ATP production above that determined by substrate availability (ADP and Pi). Using the model, we show that, under physiological conditions the rate of mitochondrial ATP production can match varying demand through substrate availability alone; that ATP production rate is not limited by the supply of reducing equivalents in the form of NADH, as a result of Ca2+ or Pi activation of the dehydrogenases; and that ATP production rate is sensitive to feedback activation of complex III by Pi. We then investigate the mechanistic implications on cytosolic ion homeostasis and force production by simulating the concentrations of cytosolic Ca2+, Na+ and K+, and activity of the key ATPases, SERCA pump, Na+/K+ pump and actin‐myosin ATPase, in response to increasing cellular energy demand. We find that feedback regulation of mitochondrial complex III by Pi improves the coupling between energy demand and mitochondrial ATP production and stabilizes cytosolic ADP and Pi concentrations. This subsequently leads to stabilized cytosolic ionic concentrations and consequentially reduced energetic cost from cellular ATPases.}, language = {en}, number = {7}, urldate = {2016-03-03}, journal = {Physiological Reports}, author = {Tran, Kenneth and Loiselle, Denis S. and Crampin, Edmund J.}, month = jul, year = {2015}, pmid = {26229005}, pages = {e12464}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\N9MHZFRS\\e12464.html:text/html;Tran et al (2015) - Regulation of cardiac cellular bioenergetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\Z6XA6P8Q\\Tran et al (2015) - Regulation of cardiac cellular bioenergetics.pdf:application/pdf} } @article{goncalves_bridging_2013, title = {Bridging the layers: towards integration of signal transduction, regulation and metabolism into mathematical models}, volume = {9}, issn = {1742-206X, 1742-2051}, shorttitle = {Bridging the layers}, url = {http://xlink.rsc.org/?DOI=c3mb25489e}, doi = {10.1039/c3mb25489e}, language = {en}, number = {7}, urldate = {2016-03-06}, journal = {Molecular BioSystems}, author = {Gonçalves, Emanuel and Bucher, Joachim and Ryll, Anke and Niklas, Jens and Mauch, Klaus and Klamt, Steffen and Rocha, Miguel and Saez-Rodriguez, Julio}, year = {2013}, pages = {1576}, file = {Gonçalves et al (2013) - Bridging the layers.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TKFCH93Z\\Gonçalves et al (2013) - Bridging the layers.pdf:application/pdf} } @article{noble_modeling_2002, title = {Modeling the {Heart}--from {Genes} to {Cells} to the {Whole} {Organ}}, volume = {295}, issn = {0036-8075, 1095-9203}, url = {http://science.sciencemag.org.ezp.lib.unimelb.edu.au/content/295/5560/1678}, doi = {10.1126/science.1069881}, abstract = {Successful physiological analysis requires an understanding of the functional interactions between the key components of cells, organs, and systems, as well as how these interactions change in disease states. This information resides neither in the genome nor even in the individual proteins that genes code for. It lies at the level of protein interactions within the context of subcellular, cellular, tissue, organ, and system structures. There is therefore no alternative to copying nature and computing these interactions to determine the logic of healthy and diseased states. The rapid growth in biological databases; models of cells, tissues, and organs; and the development of powerful computing hardware and algorithms have made it possible to explore functionality in a quantitative manner all the way from the level of genes to the physiological function of whole organs and regulatory systems. This review illustrates this development in the case of the heart. Systems physiology of the 21st century is set to become highly quantitative and, therefore, one of the most computer-intensive disciplines.}, language = {en}, number = {5560}, urldate = {2016-03-08}, journal = {Science}, author = {Noble, Denis}, month = mar, year = {2002}, pmid = {11872832}, pages = {1678--1682}, file = {Noble (2002) - Modeling the Heart--from Genes to Cells to the Whole Organ.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\F474UBRC\\Noble (2002) - Modeling the Heart--from Genes to Cells to the Whole Organ.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EJDWJV4G\\1678.html:text/html} } @article{omholt_human_2016, title = {The {Human} {Physiome}: a necessary key for the creative destruction of medicine}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, shorttitle = {The {Human} {Physiome}}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20160003}, doi = {10.1098/rsfs.2016.0003}, language = {en}, number = {2}, urldate = {2016-03-08}, journal = {Interface Focus}, author = {Omholt, Stig W. and Hunter, Peter J.}, month = apr, year = {2016}, pages = {20160003}, file = {Omholt_Hunter (2016) - The Human Physiome.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G5VKFCGJ\\Omholt_Hunter (2016) - The Human Physiome.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VV6B2IHA\\20160003.html:text/html} } @article{neal_reappraisal_2014, title = {A {Reappraisal} of {How} to {Build} {Modular}, {Reusable} {Models} of {Biological} {Systems}}, volume = {10}, issn = {1553-7358}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1003849}, doi = {10.1371/journal.pcbi.1003849}, number = {10}, urldate = {2016-03-08}, journal = {PLOS Comput Biol}, author = {Neal, Maxwell L. and Cooling, Michael T. and Smith, Lucian P. and Thompson, Christopher T. and Sauro, Herbert M. and Carlson, Brian E. and Cook, Daniel L. and Gennari, John H.}, month = oct, year = {2014}, keywords = {Chemical elements, Glucose, Glycolysis, Ontologies, Pyruvate, Simulation and modeling, Software tools, Systems Biology}, pages = {e1003849}, file = {Neal et al (2014) - A Reappraisal of How to Build Modular, Reusable Models of Biological Systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WU2P2H2C\\Neal et al (2014) - A Reappraisal of How to Build Modular, Reusable Models of Biological Systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\743GFBW5\\article.html:text/html} } @article{van_leeuwen_integrative_2009, title = {An integrative computational model for intestinal tissue renewal}, volume = {42}, copyright = {© 2009 Blackwell Publishing Ltd}, issn = {1365-2184}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/j.1365-2184.2009.00627.x/abstract}, doi = {10.1111/j.1365-2184.2009.00627.x}, abstract = {Objectives:  The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation. Methods:  At the subcellular level, deterministic models characterise molecular networks, such as cell-cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra-, inter- and extracellular cues. The modular nature of the model enables us to easily modify individual assumptions and analyse their effects on the system as a whole. Results:  We perform virtual microdissection and labelling-index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mitochondrial DNA mutation data. Conclusions:  We demonstrate that relaxing the assumption that stem-cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta-catenin levels along the crypt axis.}, language = {en}, number = {5}, urldate = {2016-03-09}, journal = {Cell Proliferation}, author = {Van Leeuwen, I. M. M. and Mirams, G. R. and Walter, A. and Fletcher, A. and Murray, P. and Osborne, J. and Varma, S. and Young, S. J. and Cooper, J. and Doyle, B. and Pitt-Francis, J. and Momtahan, L. and Pathmanathan, P. and Whiteley, J. P. and Chapman, S. J. and Gavaghan, D. J. and Jensen, O. E. and King, J. R. and Maini, P. K. and Waters, S. L. and Byrne, H. M.}, month = oct, year = {2009}, pages = {617--636}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5GJEKF6Q\\full.html:text/html;Van Leeuwen et al (2009) - An integrative computational model for intestinal tissue renewal.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5IR84F86\\Van Leeuwen et al (2009) - An integrative computational model for intestinal tissue renewal.pdf:application/pdf} } @article{christopher_data-driven_2004, title = {Data-{Driven} {Computer} {Simulation} of {Human} {Cancer} {Cell}}, volume = {1020}, issn = {1749-6632}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1196/annals.1310.014/abstract}, doi = {10.1196/annals.1310.014}, abstract = {Abstract: Using the Diagrammatic Cell Language™, Gene Network Sciences (GNS) has created a network model of interconnected signal transduction pathways and gene expression networks that control human cell proliferation and apoptosis. It includes receptor activation and mitogenic signaling, initiation of cell cycle, and passage of checkpoints and apoptosis. Time-course experiments measuring mRNA abundance and protein activity are conducted on Caco-2 and HCT 116 colon cell lines. These data were used to constrain unknown regulatory interactions and kinetic parameters via sensitivity analysis and parameter optimization methods contained in the DigitalCell™ computer simulation platform. FACS, RNA knockdown, cell growth, and apoptosis data are also used to constrain the model and to identify unknown pathways, and cross talk between known pathways will also be discussed. Using the cell simulation, GNS tested the efficacy of various drug targets and performed validation experiments to test computer simulation predictions. The simulation is a powerful tool that can in principle incorporate patient-specific data on the DNA, RNA, and protein levels for assessing efficacy of therapeutics in specific patient populations and can greatly impact success of a given therapeutic strategy.}, language = {en}, number = {1}, urldate = {2016-03-09}, journal = {Annals of the New York Academy of Sciences}, author = {Christopher, R and Dhiman, A and Fox, J and Gendelman, R and Haberitcher, T and Kagle, D and Spizz, G and Khalil, I G. and Hill, C}, month = may, year = {2004}, keywords = {Cancer, cell, computer, data, Diagrammatic Cell Language (DCL), DigitalCell, drug, Gene Network Sciences (GNS), model, simulation}, pages = {132--153}, file = {Christopher et al (2004) - Data-Driven Computer Simulation of Human Cancer Cell.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BQ2SQATG\\Christopher et al (2004) - Data-Driven Computer Simulation of Human Cancer Cell.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JRK5XN2U\\full.html:text/html} } @article{walker_models_2016, title = {Models and {Simulations} as a {Service}: {Exploring} the {Use} of {Galaxy} for {Delivering} {Computational} {Models}}, volume = {110}, issn = {0006-3495}, shorttitle = {Models and {Simulations} as a {Service}}, url = {http://www.cell.com/article/S0006349516000886/abstract}, doi = {10.1016/j.bpj.2015.12.041}, language = {English}, number = {5}, urldate = {2016-03-09}, journal = {Biophysical Journal}, author = {Walker, Mark A. and Madduri, Ravi and Rodriguez, Alex and Greenstein, Joseph L. and Winslow, Raimond L.}, month = mar, year = {2016}, pages = {1038--1043}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S96KIGNT\\S0006-3495(16)00088-6.html:text/html;Walker et al (2016) - Models and Simulations as a Service.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8TBIHBTC\\Walker et al (2016) - Models and Simulations as a Service.pdf:application/pdf} } @article{greenstein_mechanisms_2006, title = {Mechanisms of {Excitation}-{Contraction} {Coupling} in an {Integrative} {Model} of the {Cardiac} {Ventricular} {Myocyte}}, volume = {90}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349506721920}, doi = {10.1529/biophysj.105.065169}, abstract = {It is now well established that characteristic properties of excitation-contraction (EC) coupling in cardiac myocytes, such as high gain and graded Ca2+ release, arise from the interactions that occur between L-type Ca2+ channels (LCCs) and nearby ryanodine-sensitive Ca2+ release channels (RyRs) in localized microdomains. Descriptions of Ca2+-induced Ca2+ release (CICR) that account for these local mechanisms are lacking from many previous models of the cardiac action potential, and those that do include local control of CICR are able to reconstruct properties of EC coupling, but require computationally demanding stochastic simulations of ∼105 individual ion channels. In this study, we generalize a recently developed analytical approach for deriving simplified mechanistic models of CICR to formulate an integrative model of the canine cardiac myocyte which is computationally efficient. The resulting model faithfully reproduces experimentally measured properties of EC coupling and whole cell phenomena. The model is used to study the role of local redundancy in L-type Ca2+ channel gating and the role of dyad configuration on EC coupling. Simulations suggest that the characteristic steep rise in EC coupling gain observed at hyperpolarized potentials is a result of increased functional coupling between LCCs and RyRs. We also demonstrate mechanisms by which alterations in the early repolarization phase of the action potential, resulting from reduction of the transient outward potassium current, alters properties of EC coupling.}, number = {1}, urldate = {2016-03-09}, journal = {Biophysical Journal}, author = {Greenstein, Joseph L. and Hinch, Robert and Winslow, Raimond L.}, month = jan, year = {2006}, pages = {77--91}, file = {Greenstein et al (2006) - Mechanisms of Excitation-Contraction Coupling in an Integrative Model of the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U2F6V3UQ\\Greenstein et al (2006) - Mechanisms of Excitation-Contraction Coupling in an Integrative Model of the.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SJ697796\\S0006349506721920.html:text/html} } @article{kellen_integrative_2003, title = {An integrative model of coupled water and solute exchange in the heart}, volume = {285}, copyright = {Copyright © 2003 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/285/3/H1303}, doi = {10.1152/ajpheart.00933.2001}, abstract = {Physiologists have devised many models for interpreting water and solute exchange data in whole organs, but the models have typically neglected key aspects of the underlying physiology to present the simplest possible model for a given experimental situation. We have developed a physiologically realistic model of microcirculatory water and solute exchange and applied it to diverse observations of water and solute exchange in the heart. Model simulations are consistent with the results of osmotic weight transient, tracer indicator dilution, and steady-state lymph sampling experiments. The key model features that permit this unification are the use of an axially distributed blood-tissue exchange region, inclusion of a lymphatic drain in the interstitium, and the independent computation of transcapillary solute and solvent fluxes through three different pathways.}, language = {en}, number = {3}, urldate = {2016-03-09}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Kellen, Michael R. and Bassingthwaighte, James B.}, month = sep, year = {2003}, pmid = {12388252}, pages = {H1303--H1316}, file = {Kellen_Bassingthwaighte (2003) - An integrative model of coupled water and solute exchange in the heart.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KMU48NNK\\Kellen_Bassingthwaighte (2003) - An integrative model of coupled water and solute exchange in the heart.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KI5R2GVW\\H1303.html:text/html} } @article{palsson_challenges_2000, title = {The challenges of in silico biology}, volume = {18}, url = {http://www.lmbe.seu.edu.cn/biology/BESS/biology/pdf/1098.pdf}, number = {11}, urldate = {2016-03-09}, journal = {Nature biotechnology}, author = {Palsson, Bernhard and {others}}, year = {2000}, pages = {1147--1150}, file = {Palsson_others (2000) - The challenges of in silico biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XUAFQ77U\\Palsson_others (2000) - The challenges of in silico biology.pdf:application/pdf} } @article{villaverde_reverse_2014, title = {Reverse engineering and identification in systems biology: strategies, perspectives and challenges}, volume = {11}, copyright = {. © 2013 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/3.0/, which permits unrestricted use, provided the original author and source are credited.}, issn = {1742-5689, 1742-5662}, shorttitle = {Reverse engineering and identification in systems biology}, url = {http://rsif.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/11/91/20130505}, doi = {10.1098/rsif.2013.0505}, abstract = {The interplay of mathematical modelling with experiments is one of the central elements in systems biology. The aim of reverse engineering is to infer, analyse and understand, through this interplay, the functional and regulatory mechanisms of biological systems. Reverse engineering is not exclusive of systems biology and has been studied in different areas, such as inverse problem theory, machine learning, nonlinear physics, (bio)chemical kinetics, control theory and optimization, among others. However, it seems that many of these areas have been relatively closed to outsiders. In this contribution, we aim to compare and highlight the different perspectives and contributions from these fields, with emphasis on two key questions: (i) why are reverse engineering problems so hard to solve, and (ii) what methods are available for the particular problems arising from systems biology?}, language = {en}, number = {91}, urldate = {2016-03-09}, journal = {Journal of The Royal Society Interface}, author = {Villaverde, Alejandro F. and Banga, Julio R.}, month = feb, year = {2014}, pmid = {24307566}, pages = {20130505}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IA9V5FA8\\20130505.html:text/html;Villaverde_Banga (2014) - Reverse engineering and identification in systems biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VT8FMART\\Villaverde_Banga (2014) - Reverse engineering and identification in systems biology.pdf:application/pdf} } @article{machado_modeling_2011, title = {Modeling formalisms in systems biology}, volume = {1}, url = {http://www.biomedcentral.com.ezp.lib.unimelb.edu.au/content/pdf/2191-0855-1-45.pdf}, number = {1}, urldate = {2016-03-09}, journal = {AMB express}, author = {Machado, Daniel and Costa, Rafael S. and Rocha, Miguel and Ferreira, Eugénio C. and Tidor, Bruce and Rocha, Isabel}, year = {2011}, pages = {1--14}, file = {Machado et al (2011) - Modeling formalisms in systems biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VQRAEV98\\Machado et al (2011) - Modeling formalisms in systems biology.pdf:application/pdf} } @article{kauffman_advances_2003, title = {Advances in flux balance analysis}, volume = {14}, issn = {0958-1669}, url = {http://www.sciencedirect.com/science/article/pii/S0958166903001174}, doi = {10.1016/j.copbio.2003.08.001}, abstract = {Biology is going through a paradigm shift from reductionist to holistic, systems-based approaches. The complete genome sequence for a number of organisms is available and the analysis of genome sequence data is proving very useful. Thus, genome sequencing projects and bioinformatic analyses are leading to a complete ‘parts catalog’ of the molecular components in many organisms. The next challenge will be to reconstruct and simulate overall cellular functions based on the extensive reductionist information. Recent advances have been made in the area of flux balance analysis, a mathematical modeling approach often utilized by metabolic engineers to quantitatively simulate microbial metabolism.}, number = {5}, urldate = {2016-03-09}, journal = {Current Opinion in Biotechnology}, author = {Kauffman, Kenneth J and Prakash, Purusharth and Edwards, Jeremy S}, month = oct, year = {2003}, pages = {491--496}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NMI5EBX9\\S0958166903001174.html:text/html} } @article{karr_whole-cell_2012, title = {A {Whole}-{Cell} {Computational} {Model} {Predicts} {Phenotype} from {Genotype}}, volume = {150}, issn = {0092-8674}, url = {http://www.sciencedirect.com/science/article/pii/S0092867412007763}, doi = {10.1016/j.cell.2012.05.044}, abstract = {Summary Understanding how complex phenotypes arise from individual molecules and their interactions is a primary challenge in biology that computational approaches are poised to tackle. We report a whole-cell computational model of the life cycle of the human pathogen Mycoplasma genitalium that includes all of its molecular components and their interactions. An integrative approach to modeling that combines diverse mathematics enabled the simultaneous inclusion of fundamentally different cellular processes and experimental measurements. Our whole-cell model accounts for all annotated gene functions and was validated against a broad range of data. The model provides insights into many previously unobserved cellular behaviors, including in vivo rates of protein-DNA association and an inverse relationship between the durations of DNA replication initiation and replication. In addition, experimental analysis directed by model predictions identified previously undetected kinetic parameters and biological functions. We conclude that comprehensive whole-cell models can be used to facilitate biological discovery.}, number = {2}, urldate = {2016-03-09}, journal = {Cell}, author = {Karr, Jonathan R. and Sanghvi, Jayodita C. and Macklin, Derek N. and Gutschow, Miriam V. and Jacobs, Jared M. and Bolival Jr., Benjamin and Assad-Garcia, Nacyra and Glass, John I. and Covert, Markus W.}, month = jul, year = {2012}, pages = {389--401}, file = {Karr et al (2012) - A Whole-Cell Computational Model Predicts Phenotype from Genotype.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UQTFWTFK\\Karr et al (2012) - A Whole-Cell Computational Model Predicts Phenotype from Genotype.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HBHNHE96\\S0092867412007763.html:text/html} } @article{cornish-bowden_understanding_2004, title = {Understanding the parts in terms of the whole}, volume = {96}, copyright = {2004 Société Française des Microscopies and Société Biologie Cellulaire de France}, issn = {1768-322X}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1016/j.biolcel.2004.06.006/abstract}, doi = {10.1016/j.biolcel.2004.06.006}, abstract = {Abstract Metabolism is usually treated as a set of chemical reactions catalysed by separate enzymes. However, various complications, such as transport of molecules across membranes, physical association of different enzymes, giving the possibility of metabolite channelling, need to be taken into account. More generally, a proper understanding of the nature of life will require metabolism to be treated as a complete system, and not just as a collection of components. Certain properties of metabolic systems, such as feedback inhibition of the first committed step of a pathway, make sense only if one takes a broader view of a pathway than is usual in textbooks, so that one can appreciate ideas such as regulation of biosynthesis according to demand. More generally still, consideration of metabolism as a whole puts the emphasis on certain systemic aspects that are crucial but which can pass unnoticed if attention is always focussed on details. For example, a living organism, unlike any machine known or conceivable at present, makes and maintains itself and all of its components. Any serious investigation of how this can be possible implies an infinite regress in which each set of enzymes needed for the metabolic activity of the organism implies the existence of another set of enzymes to maintain them, which, in turn, implies another set, and so on indefinitely. Avoiding this implication of infinite regress represents a major challenge for future investigation.}, language = {en}, number = {9}, urldate = {2016-03-10}, journal = {Biology of the Cell}, author = {Cornish-Bowden, Athel and Cárdenas, María Luz and Letelier, Juan-Carlos and Soto-Andrade, Jorge and Abarzúa, Flavio Guíñez}, month = dec, year = {2004}, keywords = {Metabolism, Metabolism-repair systems, (M,R)-systems, Systems Biology}, pages = {713--717}, file = {Cornish-Bowden et al (2004) - Understanding the parts in terms of the whole.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5R6FVVW9\\Cornish-Bowden et al (2004) - Understanding the parts in terms of the whole.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SZGPWI8D\\abstract.html:text/html} } @article{walpole_multiscale_2013, title = {Multiscale {Computational} {Models} of {Complex} {Biological} {Systems}}, volume = {15}, issn = {1523-9829}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3970111/}, doi = {10.1146/annurev-bioeng-071811-150104}, abstract = {Integration of data across spatial, temporal, and functional scales is a primary focus of biomedical engineering efforts. The advent of powerful computing platforms, coupled with quantitative data from high-throughput experimental platforms, has allowed multiscale modeling to expand as a means to more comprehensively investigate biological phenomena in experimentally relevant ways. This review aims to highlight recently published multiscale models of biological systems while using their successes to propose the best practices for future model development. We demonstrate that coupling continuous and discrete systems best captures biological information across spatial scales by selecting modeling techniques that are suited to the task. Further, we suggest how to best leverage these multiscale models to gain insight into biological systems using quantitative, biomedical engineering methods to analyze data in non-intuitive ways. These topics are discussed with a focus on the future of the field, the current challenges encountered, and opportunities yet to be realized.}, urldate = {2016-03-09}, journal = {Annual review of biomedical engineering}, author = {Walpole, Joseph and Papin, Jason A. and Peirce, Shayn M.}, year = {2013}, pmid = {23642247}, pmcid = {PMC3970111}, pages = {137--154}, file = {Walpole et al (2013) - Multiscale Computational Models of Complex Biological Systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZBH5GPRD\\Walpole et al (2013) - Multiscale Computational Models of Complex Biological Systems.pdf:application/pdf} } @article{patel_role_2011, title = {The {Role} of {Model} {Integration} in {Complex} {Systems} {Research}}, url = {https://www.scs.org/magazines/2011-01/index_file/Files/Patel_ED(2).pdf}, urldate = {2016-04-21}, journal = {SCS M\&S Magazine}, author = {Patel, Manish and Nagl, Sylvia}, year = {2011}, file = {Patel_Nagl - The Role of Model Integration in Complex Systems Research.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I499RQRZ\\Patel_Nagl - The Role of Model Integration in Complex Systems Research.pdf:application/pdf} } @article{smith_computational_2007, title = {Computational biology of cardiac myocytes: proposed standards for the physiome}, volume = {210}, copyright = {© The Company of Biologists Limited 2007}, issn = {0022-0949, 1477-9145}, shorttitle = {Computational biology of cardiac myocytes}, url = {http://jeb.biologists.org/content/210/9/1576}, doi = {10.1242/jeb.000133}, language = {en}, number = {9}, urldate = {2016-04-28}, journal = {Journal of Experimental Biology}, author = {Smith, Nicolas P. and Crampin, Edmund J. and Niederer, Steven A. and Bassingthwaighte, James B. and Beard, Daniel A.}, month = may, year = {2007}, pmid = {17449822}, keywords = {cardiac, Mathematical modelling, multi-scale, physiome}, pages = {1576--1583}, file = {Smith et al (2007) - Computational biology of cardiac myocytes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GJ9GFGHS\\Smith et al (2007) - Computational biology of cardiac myocytes.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\69N2P642\\1576.html:text/html} } @article{covert_transcriptional_2002, title = {Transcriptional {Regulation} in {Constraints}-based {Metabolic} {Models} of {Escherichia} coli}, volume = {277}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/277/31/28058}, abstract = {Full genome sequences enable the construction of genome-scale in silico models of complex cellular functions. Genome-scale constraints-based models of Escherichia coli metabolism have been constructed and used to successfully interpret and predict cellular behavior under a range of conditions. These previous models do not account for regulation of gene transcription and thus cannot accurately predict some organism functions. Here we present an in silico model of the central E. coli metabolism that accounts for regulation of gene expression. This model accounts for 149 genes, the products of which include 16 regulatory proteins and 73 enzymes. These enzymes catalyze 113 reactions, 45 of which are controlled by transcriptional regulation. The combined metabolic/regulatory model can predict the ability of mutant E. coli strains to grow on defined media as well as time courses of cell growth, substrate uptake, metabolic by-product secretion, and qualitative gene expression under various conditions, as indicated by comparison with experimental data under a variety of environmental conditions. The in silico model may also be used to interpret dynamic behaviors observed in cell cultures. This combined metabolic/regulatory model is thus an important step toward the goal of synthesizing genome-scale models that accurately represent E. coli behavior.}, language = {en}, number = {31}, urldate = {2016-03-10}, journal = {Journal of Biological Chemistry}, author = {Covert, Markus W. and Palsson, Bernhard Ø}, month = aug, year = {2002}, pages = {28058--28064}, file = {Covert_Palsson (2002) - Transcriptional Regulation in Constraints-based Metabolic Models of Escherichia.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DAE22PGI\\Covert_Palsson (2002) - Transcriptional Regulation in Constraints-based Metabolic Models of Escherichia.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6DH32QFZ\\28058.html:text/html} } @article{shlomi_genome-scale_2007, title = {A genome-scale computational study of the interplay between transcriptional regulation and metabolism}, volume = {3}, issn = {1744-4292}, url = {http://msb.embopress.org/cgi/doi/10.1038/msb4100141}, doi = {10.1038/msb4100141}, urldate = {2016-03-10}, journal = {Molecular Systems Biology}, author = {Shlomi, Tomer and Eisenberg, Yariv and Sharan, Roded and Ruppin, Eytan}, month = apr, year = {2007}, file = {Shlomi et al (2007) - A genome-scale computational study of the interplay between transcriptional.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GTVHT23C\\Shlomi et al (2007) - A genome-scale computational study of the interplay between transcriptional.pdf:application/pdf} } @article{covert_integrating_2008, title = {Integrating metabolic, transcriptional regulatory and signal transduction models in {Escherichia} coli}, volume = {24}, issn = {1367-4803, 1460-2059}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/24/18/2044}, doi = {10.1093/bioinformatics/btn352}, abstract = {Motivation: The effort to build a whole-cell model requires the development of new modeling approaches, and in particular, the integration of models for different types of processes, each of which may be best described using different representation. Flux-balance analysis (FBA) has been useful for large-scale analysis of metabolic networks, and methods have been developed to incorporate transcriptional regulation (regulatory FBA, or rFBA). Of current interest is the integration of these approaches with detailed models based on ordinary differential equations (ODEs). Results: We developed an approach to modeling the dynamic behavior of metabolic, regulatory and signaling networks by combining FBA with regulatory Boolean logic, and ordinary differential equations. We use this approach (called integrated FBA, or iFBA) to create an integrated model of Escherichia coli which combines a flux-balance-based, central carbon metabolic and transcriptional regulatory model with an ODE-based, detailed model of carbohydrate uptake control. We compare the predicted Escherichia coli wild-type and single gene perturbation phenotypes for diauxic growth on glucose/lactose and glucose/glucose-6-phosphate with that of the individual models. We find that iFBA encapsulates the dynamics of three internal metabolites and three transporters inadequately predicted by rFBA. Furthermore, we find that iFBA predicts different and more accurate phenotypes than the ODE model for 85 of 334 single gene perturbation simulations, as well for the wild-type simulations. We conclude that iFBA is a significant improvement over the individual rFBA and ODE modeling paradigms. Availability: All MATLAB files used in this study are available at http://www.simtk.org/home/ifba/. Contact: covert@stanford.edu Supplementary information:Supplementary data are available at Bioinformatics online.}, language = {en}, number = {18}, urldate = {2016-03-10}, journal = {Bioinformatics}, author = {Covert, Markus W. and Xiao, Nan and Chen, Tiffany J. and Karr, Jonathan R.}, month = sep, year = {2008}, pmid = {18621757}, pages = {2044--2050}, file = {Covert et al (2008) - Integrating metabolic, transcriptional regulatory and signal transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WW46TQSZ\\Covert et al (2008) - Integrating metabolic, transcriptional regulatory and signal transduction.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FTZFTIH9\\2044.html:text/html} } @article{lloyd_cellml:_2004, series = {Modelling {Cellular} and {Tissue} {Function}}, title = {{CellML}: its future, present and past}, volume = {85}, issn = {0079-6107}, shorttitle = {{CellML}}, url = {http://www.sciencedirect.com/science/article/pii/S007961070400015X}, doi = {10.1016/j.pbiomolbio.2004.01.004}, abstract = {Advances in biotechnology and experimental techniques have lead to the elucidation of vast amounts of biological data. Mathematical models provide a method of analysing this data; however, there are two issues that need to be addressed: (1) the need for standards for defining cell models so they can, for example, be exchanged across the World Wide Web, and also read into simulation software in a consistent format and (2) eliminating the errors which arise with the current method of model publication. CellML has evolved to meet these needs of the modelling community. CellML is a free, open-source, eXtensible markup language based standard for defining mathematical models of cellular function. In this paper we summarise the structure of CellML, its current applications (including biological pathway and electrophysiological models), and its future development—in particular, the development of toolsets and the integration of ontologies.}, number = {2–3}, urldate = {2016-03-11}, journal = {Progress in Biophysics and Molecular Biology}, author = {Lloyd, Catherine M. and Halstead, Matt D. B. and Nielsen, Poul F.}, month = jun, year = {2004}, keywords = {CellML, Markup language, Mathematical modelling, Ontologies, XML}, pages = {433--450}, file = {Lloyd et al (2004) - CellML.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\X6T5R5JA\\Lloyd et al (2004) - CellML.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D49SF628\\S007961070400015X.html:text/html} } @article{mallavarapu_programming_2009, title = {Programming with models: modularity and abstraction provide powerful capabilities for systems biology}, volume = {6}, copyright = {© 2008 The Royal Society}, issn = {1742-5689, 1742-5662}, shorttitle = {Programming with models}, url = {http://rsif.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/32/257}, doi = {10.1098/rsif.2008.0205}, abstract = {Mathematical models are increasingly used to understand how phenotypes emerge from systems of molecular interactions. However, their current construction as monolithic sets of equations presents a fundamental barrier to progress. Overcoming this requires modularity, enabling sub-systems to be specified independently and combined incrementally, and abstraction, enabling generic properties of biological processes to be specified independently of specific instances. These, in turn, require models to be represented as programs rather than as datatypes. Programmable modularity and abstraction enables libraries of modules to be created, which can be instantiated and reused repeatedly in different contexts with different components. We have developed a computational infrastructure that accomplishes this. We show here why such capabilities are needed, what is required to implement them and what can be accomplished with them that could not be done previously.}, language = {en}, number = {32}, urldate = {2016-03-11}, journal = {Journal of The Royal Society Interface}, author = {Mallavarapu, Aneil and Thomson, Matthew and Ullian, Benjamin and Gunawardena, Jeremy}, month = mar, year = {2009}, pmid = {18647734}, pages = {257--270}, file = {Mallavarapu et al (2009) - Programming with models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9FUTFXW2\\Mallavarapu et al (2009) - Programming with models.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ISARXNZ8\\257.html:text/html} } @article{hucka_systems_2003, title = {The systems biology markup language ({SBML}): a medium for representation and exchange of biochemical network models}, volume = {19}, issn = {1367-4803, 1460-2059}, shorttitle = {The systems biology markup language ({SBML})}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/19/4/524}, doi = {10.1093/bioinformatics/btg015}, abstract = {Motivation: Molecular biotechnology now makes it possible to build elaborate systems models, but the systems biology community needs information standards if models are to be shared, evaluated and developed cooperatively. Results: We summarize the Systems Biology Markup Language (SBML) Level 1, a free, open, XML-based format for representing biochemical reaction networks. SBML is a software-independent language for describing models common to research in many areas of computational biology, including cell signaling pathways, metabolic pathways, gene regulation, and others. Availability: The specification of SBML Level 1 is freely available from http://www.sbml.org/ Contact: sysbio-team@caltech.edu}, language = {en}, number = {4}, urldate = {2016-03-11}, journal = {Bioinformatics}, author = {Hucka, M. and Finney, A. and Sauro, H. M. and Bolouri, H. and Doyle, J. C. and Kitano, H. and Forum, {and} the rest of the SBML and Arkin, A. P. and Bornstein, B. J. and Bray, D. and Cornish-Bowden, A. and Cuellar, A. A. and Dronov, S. and Gilles, E. D. and Ginkel, M. and Gor, V. and Goryanin, I. I. and Hedley, W. J. and Hodgman, T. C. and Hofmeyr, J.-H. and Hunter, P. J. and Juty, N. S. and Kasberger, J. L. and Kremling, A. and Kummer, U. and Novère, N. Le and Loew, L. M. and Lucio, D. and Mendes, P. and Minch, E. and Mjolsness, E. D. and Nakayama, Y. and Nelson, M. R. and Nielsen, P. F. and Sakurada, T. and Schaff, J. C. and Shapiro, B. E. and Shimizu, T. S. and Spence, H. D. and Stelling, J. and Takahashi, K. and Tomita, M. and Wagner, J. and Wang, J.}, month = mar, year = {2003}, pmid = {12611808}, pages = {524--531}, file = {Hucka et al (2003) - The systems biology markup language (SBML).pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\N5VFAFXA\\Hucka et al (2003) - The systems biology markup language (SBML).pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5TKES75U\\524.html:text/html} } @article{clerk-maxwell_remarks_1869, title = {Remarks on the {Mathematical} {Classification} of {Physical} {Quantities},}, volume = {s1-3}, issn = {0024-6115, 1460-244X}, url = {http://plms.oxfordjournals.org/cgi/doi/10.1112/plms/s1-3.1.224}, doi = {10.1112/plms/s1-3.1.224}, language = {en}, number = {1}, urldate = {2016-05-02}, journal = {Proceedings of the London Mathematical Society}, author = {Clerk-Maxwell, J.}, month = nov, year = {1869}, pages = {224--233}, file = {Clerk-Maxwell (1869) - Remarks on the Mathematical Classification of Physical Quantities,.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7N94FKB6\\Clerk-Maxwell (1869) - Remarks on the Mathematical Classification of Physical Quantities,.pdf:application/pdf} } @article{waltemath_reproducible_2011, title = {Reproducible computational biology experiments with {SED}-{ML} - {The} {Simulation} {Experiment} {Description} {Markup} {Language}}, volume = {5}, issn = {1752-0509}, url = {http://www.biomedcentral.com/1752-0509/5/198}, doi = {10.1186/1752-0509-5-198}, language = {en}, number = {1}, urldate = {2016-03-11}, journal = {BMC Systems Biology}, author = {Waltemath, Dagmar and Adams, Richard and Bergmann, Frank T and Hucka, Michael and Kolpakov, Fedor and Miller, Andrew K and Moraru, Ion I and Nickerson, David and Sahle, Sven and Snoep, Jacky L and Le Novère, Nicolas}, year = {2011}, pages = {198} } @book{beard_chemical_2008, address = {Cambridge; New York}, title = {Chemical biophysics quantitative analysis of cellular systems}, isbn = {978-0-521-87070-2 978-0-511-64973-8 978-0-511-80334-5 978-0-511-39814-8}, abstract = {'Chemical Biophysics' provides an engineering-based approach to biochemical system analysis for courses on systems biology, computational bioengineering and molecular biophysics. It applies physical chemistry principles to mathematical and computational modeling of biochemical systems for an interdisciplinary audience.}, language = {English}, urldate = {2016-03-15}, publisher = {Cambridge University Press}, author = {Beard, Daniel A and Qian, Hong}, year = {2008}, file = {Beard_Qian (2008) - Chemical biophysics quantitative analysis of cellular systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RX9EJS44\\Beard_Qian (2008) - Chemical biophysics quantitative analysis of cellular systems.pdf:application/pdf} } @article{kolczyk_challenges_2016, title = {Challenges in horizontal model integration}, volume = {10}, issn = {1752-0509}, url = {http://www.biomedcentral.com/1752-0509/10/28}, doi = {10.1186/s12918-016-0266-3}, language = {en}, number = {1}, urldate = {2016-03-17}, journal = {BMC Systems Biology}, author = {Kolczyk, Katrin and Conradi, Carsten}, month = dec, year = {2016}, file = {Kolczyk_Conradi (2016) - Challenges in horizontal model integration.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AJXKAHU9\\Kolczyk_Conradi (2016) - Challenges in horizontal model integration.pdf:application/pdf} } @article{kohl_systems_2010, title = {Systems {Biology}: {An} {Approach}}, volume = {88}, copyright = {© 2010 American Society for Clinical Pharmacology and Therapeutics}, issn = {1532-6535}, shorttitle = {Systems {Biology}}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1038/clpt.2010.92/abstract}, doi = {10.1038/clpt.2010.92}, abstract = {In just over a decade, Systems Biology has moved from being an idea, or rather a disparate set of ideas, to a mainstream feature of research and funding priorities. Institutes, departments, and centers of various flavors of Systems Biology have sprung up all over the world. An Internet search now produces more than 2 million hits. Of the 2,800 entries in PubMed with “Systems Biology” in either the title or the abstract, only two papers were published before 2000, and {\textgreater}90\% were published in the past five years. In this article, we interpret Systems Biology as an approach rather than as a field or a destination of research. We illustrate that this approach is productive for the exploration of systems behavior, or “phenotypes,” at all levels of structural and functional complexity, explicitly including the supracellular domain, and suggest how this may be related conceptually to genomes and biochemical networks. We discuss the role of models in Systems Biology and conclude with a consideration of their utility in biomedical research and development. Clinical Pharmacology \& Therapeutics (2010) 88 1, 25–33. doi: 10.1038/clpt.2010.92}, language = {en}, number = {1}, urldate = {2016-03-21}, journal = {Clinical Pharmacology \& Therapeutics}, author = {Kohl, P and Crampin, E J and Quinn, T A and Noble, D}, month = jul, year = {2010}, pages = {25--33}, file = {Kohl et al (2010) - Systems Biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RN8853SG\\Kohl et al (2010) - Systems Biology.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RKW53UXD\\abstract.html:text/html} } @article{sueur_bond-graph_1991, title = {Bond-graph approach for structural analysis of {MIMO} linear systems}, volume = {328}, issn = {0016-0032}, url = {http://www.sciencedirect.com/science/article/pii/001600329190006O}, doi = {10.1016/0016-0032(91)90006-O}, abstract = {The study of the structural properties of MIMO systems was previously done using a graph approach. This paper presents a new method using bond-graph methodology to derive information on structural controllability/observability properties of a system. The notion of structural rank is defined, and causal manipulations of the bond-graph model carried out in order to determine graphically the non-controllable or non-observable state subspaces. A procedure is described which allows one to find the minimum number of actuators and sensors necessary for control and observation, and to optimize their positions in the system in order to simplify state feedback control laws.}, number = {1}, urldate = {2016-03-21}, journal = {Journal of the Franklin Institute}, author = {Sueur, C. and Dauphin-Tanguy, G.}, month = jan, year = {1991}, pages = {55--70}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EFHF4DXU\\001600329190006O.html:text/html;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GIR9H8J5\\001600329190006O.html:text/html;Sueur_Dauphin-Tanguy (1991) - Bond-graph approach for structural analysis of MIMO linear systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QFSMCMJQ\\Sueur_Dauphin-Tanguy (1991) - Bond-graph approach for structural analysis of MIMO linear systems.pdf:application/pdf} } @article{qian_thermodynamics_2005, title = {Thermodynamics of stoichiometric biochemical networks in living systems far from equilibrium}, volume = {114}, issn = {0301-4622}, url = {http://www.sciencedirect.com/science/article/pii/S030146220400314X}, doi = {10.1016/j.bpc.2004.12.001}, abstract = {The principles of thermodynamics apply to both equilibrium and nonequilibrium biochemical systems. The mathematical machinery of the classic thermodynamics, however, mainly applies to systems in equilibrium. We introduce a thermodynamic formalism for the study of metabolic biochemical reaction (open, nonlinear) networks in both time-dependent and time-independent nonequilibrium states. Classical concepts in equilibrium thermodynamics–enthalpy, entropy, and Gibbs free energy of biochemical reaction systems–are generalized to nonequilibrium settings. Chemical motive force, heat dissipation rate, and entropy production (creation) rate, key concepts in nonequilibrium systems, are introduced. Dynamic equations for the thermodynamic quantities are presented in terms of the key observables of a biochemical network: stoichiometric matrix Q, reaction fluxes J, and chemical potentials of species μ without evoking empirical rate laws. Energy conservation and the Second Law are established for steady-state and dynamic biochemical networks. The theory provides the physiochemical basis for analyzing large-scale metabolic networks in living organisms.}, number = {2–3}, urldate = {2016-03-22}, journal = {Biophysical Chemistry}, author = {Qian, Hong and Beard, Daniel A.}, month = apr, year = {2005}, keywords = {Biological networks, Cycle kinetics, Mathematical modeling, Metabolism, Systems Biology}, pages = {213--220}, file = {Qian_Beard (2005) - Thermodynamics of stoichiometric biochemical networks in living systems far.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DJXMRTIJ\\Qian_Beard (2005) - Thermodynamics of stoichiometric biochemical networks in living systems far.pdf:application/pdf;Qian_Beard (2005) - Thermodynamics of stoichiometric biochemical networks in living systems far.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ARQDGHW7\\Qian_Beard (2005) - Thermodynamics of stoichiometric biochemical networks in living systems far.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UX3PMEWW\\S030146220400314X.html:text/html;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JIE7JRBI\\S030146220400314X.html:text/html} } @article{garcia_thermodynamics_2011, title = {Thermodynamics of {Biological} {Processes}}, volume = {492}, issn = {0076-6879}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3264492/}, doi = {10.1016/B978-0-12-381268-1.00014-8}, abstract = {There is a long and rich tradition of using ideas from both equilibrium thermodynamics and its microscopic partner theory of equilibrium statistical mechanics. In this chapter, we provide some background on the origins of the seemingly unreasonable effectiveness of ideas from both thermodynamics and statistical mechanics in biology. After making a description of these foundational issues, we turn to a series of case studies primarily focused on binding that are intended to illustrate the broad biological reach of equilibrium thinking in biology. These case studies include ligand-gated ion channels, thermodynamic models of transcription, and recent applications to the problem of bacterial chemotaxis. As part of the description of these case studies, we explore a number of different uses of the famed Monod–Wyman–Changeux (MWC) model as a generic tool for providing a mathematical characterization of two-state systems. These case studies should provide a template for tailoring equilibrium ideas to other problems of biological interest.}, urldate = {2016-03-22}, journal = {Methods in Enzymology}, author = {Garcia, Hernan G. and Kondev, Jane and Orme, Nigel and Theriot, Julie A. and Phillips, Rob}, year = {2011}, pmid = {21333788}, pmcid = {PMC3264492}, pages = {27--59}, file = {Garcia et al (2011) - Thermodynamics of Biological Processes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FRR28A5Z\\Garcia et al (2011) - Thermodynamics of Biological Processes.pdf:application/pdf} } @article{gawthrop_hierarchical_2015, title = {Hierarchical bond graph modelling of biochemical networks}, volume = {471}, copyright = {© 2015 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licence}, issn = {1364-5021, 1471-2946}, url = {http://rspa.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/471/2184/20150642}, doi = {10.1098/rspa.2015.0642}, abstract = {The bond graph approach to modelling biochemical networks is extended to allow hierarchical construction of complex models from simpler components. This is made possible by representing the simpler components as thermodynamically open systems exchanging mass and energy via ports. A key feature of this approach is that the resultant models are robustly thermodynamically compliant: the thermodynamic compliance is not dependent on precise numerical values of parameters. Moreover, the models are reusable owing to the well-defined interface provided by the energy ports. To extract bond graph model parameters from parameters found in the literature, general and compact formulae are developed to relate free-energy constants and equilibrium constants. The existence and uniqueness of solutions is considered in terms of fundamental properties of stoichiometric matrices. The approach is illustrated by building a hierarchical bond graph model of glycogenolysis in skeletal muscle.}, language = {en}, number = {2184}, urldate = {2016-03-31}, journal = {Proc. R. Soc. A}, author = {Gawthrop, Peter J. and Cursons, Joseph and Crampin, Edmund J.}, month = dec, year = {2015}, keywords = {Bond graphs, Quantitative Biology - Molecular Networks, Quantitative Biology - Quantitative Methods}, pages = {20150642}, annote = {Comment: 35 pages, 12 figures}, file = {arXiv.org Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W7ABDXNW\\1503.html:text/html;Gawthrop et al (2015) - Hierarchical bond graph modelling of biochemical networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NIWMNRVG\\Gawthrop et al (2015) - Hierarchical bond graph modelling of biochemical networks.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PR3D3X4P\\20150642.html:text/html} } @article{crampin_dynamic_2006, title = {A {Dynamic} {Model} of {Excitation}-{Contraction} {Coupling} during {Acidosis} in {Cardiac} {Ventricular} {Myocytes}}, volume = {90}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349506724900}, doi = {10.1529/biophysj.105.070557}, abstract = {Acidosis in cardiac myocytes is a major factor in the reduced inotropy that occurs in the ischemic heart. During acidosis, diastolic calcium concentration and the amplitude of the calcium transient increase, while the strength of contraction decreases. This has been attributed to the inhibition by protons of calcium uptake and release by the sarcoplasmic reticulum, to a rise of intracellular sodium caused by activation of sodium-hydrogen exchange, decreased calcium binding affinity to Troponin-C, and direct effects on the contractile machinery. The relative contributions and concerted action of these effects are, however, difficult to establish experimentally. We have developed a mathematical model to examine altered calcium-handling mechanisms during acidosis. Each of the alterations was incorporated into a dynamical model of pH regulation and excitation-contraction coupling to predict the time courses of key ionic species during acidosis, in particular intracellular pH, sodium and the calcium transient, and contraction. This modeling study suggests that the most significant effects are elevated sodium, inhibition of sodium-calcium exchange, and the direct interaction of protons with the contractile machinery; and shows how the experimental data on these contributions can be reconciled to understand the overall effects of acidosis in the beating heart.}, number = {9}, urldate = {2016-03-31}, journal = {Biophysical Journal}, author = {Crampin, Edmund J. and Smith, Nicolas P.}, month = may, year = {2006}, pages = {3074--3090}, file = {Crampin_Smith (2006) - A Dynamic Model of Excitation-Contraction Coupling during Acidosis in Cardiac.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WNM4PAA3\\Crampin_Smith (2006) - A Dynamic Model of Excitation-Contraction Coupling during Acidosis in Cardiac.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DE8V9MMK\\S0006349506724900.html:text/html} } @article{kroes_structural_1989, title = {Structural {Analogies} {Between} {Physical} {Systems}}, volume = {40}, issn = {0007-0882, 1464-3537}, url = {http://bjps.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/40/2/145}, doi = {10.1093/bjps/40.2.145}, abstract = {Structural analogies between physical laws have received considerable attention from philosospheres of science. This paper, however, focusses on structural analogies between physical systems; this type of analogy plays an important role in the physical and technological sciences. A formal, set-theoretic description of structural analogies between physical systems is presented, and it is shown that a structural analogy between systems does not require a structural analogy with regard to the laws involved, nor conversely.}, language = {en}, number = {2}, urldate = {2016-05-02}, journal = {The British Journal for the Philosophy of Science}, author = {Kroes, Peter}, month = jun, year = {1989}, pages = {145--154}, file = {Kroes (1989) - Structural Analogies Between Physical Systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3I3CAA92\\Kroes (1989) - Structural Analogies Between Physical Systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G9FJBBZE\\145.html:text/html} } @article{del_vecchio_control_2013, title = {A control theoretic framework for modular analysis and design of biomolecular networks}, volume = {37}, issn = {1367-5788}, url = {http://www.sciencedirect.com/science/article/pii/S1367578813000576}, doi = {10.1016/j.arcontrol.2013.09.011}, abstract = {Control theory has been instrumental for the analysis and design of a number of engineering systems, including aerospace and transportation systems, robotics and intelligent machines, manufacturing chains, electrical, power, and information networks. In the past several years, the ability of de novo creating biomolecular networks and of measuring key physical quantities has come to a point in which quantitative analysis and design of biological systems is possible. While a modular approach to analyze and design complex systems has proven critical in most control theory applications, it is still subject of debate whether a modular approach is viable in biomolecular networks. In fact, biomolecular networks display context-dependent behavior, that is, the input/output dynamical properties of a module change once this is part of a network. One cause of context dependence, similar to what found in many engineering systems, is retroactivity, that is, the effect of loads applied on a module by downstream systems. In this paper, we focus on retroactivity and review techniques, based on nonlinear control and dynamical systems theory, that we have developed to quantify the extent of modularity of biomolecular systems and to establish modular analysis and design techniques.}, number = {2}, urldate = {2016-04-01}, journal = {Annual Reviews in Control}, author = {Del Vecchio, Domitilla}, month = dec, year = {2013}, pages = {333--345}, file = {Del Vecchio (2013) - A control theoretic framework for modular analysis and design of biomolecular.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D8ACZ6RK\\Del Vecchio (2013) - A control theoretic framework for modular analysis and design of biomolecular.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HT8MRDPG\\S1367578813000576.html:text/html} } @article{gawthrop_modular_2016, title = {Modular bond-graph modelling and analysis of biomolecular systems}, issn = {1751-8849, 1751-8857}, url = {http://digital-library.theiet.org/content/journals/10.1049/iet-syb.2015.0083}, doi = {10.1049/iet-syb.2015.0083}, language = {en}, urldate = {2016-05-09}, journal = {IET Systems Biology}, author = {Gawthrop, Peter J. and Crampin, Edmund J.}, month = mar, year = {2016}, file = {GawCra16.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\J4VWM3BV\\GawCra16.pdf:application/pdf} } @article{geoffrion_structured_1994, title = {Structured modeling: {Survey} and future research directions}, volume = {15}, shorttitle = {Structured modeling}, number = {1}, journal = {ORSA CSTS Newsletter}, author = {Geoffrion, Arthur M.}, year = {1994}, pages = {1--20} } @article{beard_computational_2005, title = {Computational modeling of physiological systems}, volume = {23}, copyright = {Copyright © 2005 the American Physiological Society}, issn = {1094-8341, 1531-2267}, url = {http://physiolgenomics.physiology.org.ezp.lib.unimelb.edu.au/content/23/1/1}, doi = {10.1152/physiolgenomics.00117.2005}, language = {en}, number = {1}, urldate = {2016-04-28}, journal = {Physiological Genomics}, author = {Beard, Daniel A. and Bassingthwaighte, James B. and Greene, Andrew S.}, month = sep, year = {2005}, pmid = {16179418}, pages = {1--3}, file = {Beard et al (2005) - Computational modeling of physiological systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UI686MFT\\Beard et al (2005) - Computational modeling of physiological systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KBHB9NXI\\1.html:text/html} } @phdthesis{steinkellner_aircraft_2011, address = {Linköping}, title = {Aircraft vehicle systems modeling and simulation under uncertainty}, language = {English}, school = {Department of Management and Engineering, Division of Machine Design, Linköping University}, author = {Steinkellner, Sören}, year = {2011}, file = {FULLTEXT01.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JDV33SDJ\\FULLTEXT01.pdf:application/pdf} } @article{oster_chemical_1974, title = {Chemical reaction networks}, volume = {21}, issn = {0098-4094}, doi = {10.1109/TCS.1974.1083946}, abstract = {A set of chemical species "interconnected" by reaction pathways is commonly referred to as a chemical network. We show that chemical networks are mathematically equivalent to a class of multiport networks. Hence, abstract circuit theory can be applied to study chemical systems. Both linear-graph and bond-graph representations of reaction networks are presented. We also indicate how network methods can be employed to treat coupled transport and chemical reaction processes.}, number = {6}, journal = {IEEE Transactions on Circuits and Systems}, author = {Oster, G. and Perelson, A.}, month = nov, year = {1974}, keywords = {Bonding, Chemical elements, Chemical processes, Chemistry, Circuit theory, Coupling circuits, General circuits and systems theory, Integrated circuit interconnections, Interconnected networks, Kinematics, Kinetic theory, Network topology, N-path filters, Sequences, System modeling, Thermodynamics}, pages = {709--721}, file = {IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\J4NZ7VIV\\abs_all.html:text/html;Oster_Perelson (1974) - Chemical reaction networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2WM4F9WH\\Oster_Perelson (1974) - Chemical reaction networks.pdf:application/pdf} } @article{catterall_hodgkin-huxley_2012, title = {The {Hodgkin}-{Huxley} {Heritage}: {From} {Channels} to {Circuits}}, volume = {32}, issn = {0270-6474, 1529-2401}, shorttitle = {The {Hodgkin}-{Huxley} {Heritage}}, url = {http://www.jneurosci.org/content/32/41/14064}, doi = {10.1523/JNEUROSCI.3403-12.2012}, abstract = {The Hodgkin-Huxley studies of the action potential, published 60 years ago, are a central pillar of modern neuroscience research, ranging from molecular investigations of the structural basis of ion channel function to the computational implications at circuit level. In this Symposium Review, we aim to demonstrate the ongoing impact of Hodgkin's and Huxley's ideas. The Hodgkin-Huxley model established a framework in which to describe the structural and functional properties of ion channels, including the mechanisms of ion permeation, selectivity, and gating. At a cellular level, the model is used to understand the conditions that control both the rate and timing of action potentials, essential for neural encoding of information. Finally, the Hodgkin-Huxley formalism is central to computational neuroscience to understand both neuronal integration and circuit level information processing, and how these mechanisms might have evolved to minimize energy cost.}, language = {en}, number = {41}, urldate = {2016-04-29}, journal = {The Journal of Neuroscience}, author = {Catterall, William A. and Raman, Indira M. and Robinson, Hugh P. C. and Sejnowski, Terrence J. and Paulsen, Ole}, month = oct, year = {2012}, pmid = {23055474}, pages = {14064--14073}, file = {Catterall et al (2012) - The Hodgkin-Huxley Heritage.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\P9IKTGJQ\\Catterall et al (2012) - The Hodgkin-Huxley Heritage.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\Q9BJWKM3\\14064.html:text/html} } @article{bassingthwaighte_cardiac_2009, title = {The {Cardiac} {Physiome}: perspectives for the future}, volume = {94}, issn = {1469-445X}, shorttitle = {The {Cardiac} {Physiome}}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/expphysiol.2008.044099/abstract}, doi = {10.1113/expphysiol.2008.044099}, abstract = {The Physiome Project, exemplified by the Cardiac Physiome, is now 10 years old. In this article, we review past progress and future challenges in developing a quantitative framework for understanding human physiology that incorporates both genetic inheritance and environmental influence. Despite the enormity of the challenge, which is certainly greater than that facing the pioneers of the human genome project 20 years ago, there is reason for optimism that real and accelerating progress is being made.}, language = {en}, number = {5}, urldate = {2016-04-29}, journal = {Experimental Physiology}, author = {Bassingthwaighte, James and Hunter, Peter and Noble, Denis}, month = may, year = {2009}, pages = {597--605}, file = {Bassingthwaighte et al (2009) - The Cardiac Physiome.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\A3VEWF6C\\Bassingthwaighte et al (2009) - The Cardiac Physiome.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4V5BDNTQ\\abstract.html:text/html} } @article{perelson_network_1975, title = {Network thermodynamics. {An} overview.}, volume = {15}, issn = {0006-3495}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1334728/}, number = {7}, urldate = {2016-05-03}, journal = {Biophysical Journal}, author = {Perelson, A S}, month = jul, year = {1975}, pmid = {1095093}, pmcid = {PMC1334728}, pages = {667--685}, file = {Perelson (1975) - Network thermodynamics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MPN8JARF\\Perelson (1975) - Network thermodynamics.pdf:application/pdf} } @article{akaike_new_1974, title = {A new look at the statistical model identification}, volume = {19}, issn = {0018-9286}, doi = {10.1109/TAC.1974.1100705}, abstract = {The history of the development of statistical hypothesis testing in time series analysis is reviewed briefly and it is pointed out that the hypothesis testing procedure is not adequately defined as the procedure for statistical model identification. The classical maximum likelihood estimation procedure is reviewed and a new estimate minimum information theoretical criterion (AIC) estimate (MAICE) which is designed for the purpose of statistical identification is introduced. When there are several competing models the MAICE is defined by the model and the maximum likelihood estimates of the parameters which give the minimum of AIC defined by AIC = (-2)log-(maximum likelihood) + 2(number of independently adjusted parameters within the model). MAICE provides a versatile procedure for statistical model identification which is free from the ambiguities inherent in the application of conventional hypothesis testing procedure. The practical utility of MAICE in time series analysis is demonstrated with some numerical examples.}, number = {6}, journal = {IEEE Transactions on Automatic Control}, author = {Akaike, H.}, month = dec, year = {1974}, keywords = {Art, Estimation theory, History, Linear systems, Maximum likelihood estimation, maximum-likelihood (ML) estimation, Parameter identification, Roundoff errors, Sampling methods, Stochastic processes, Testing, Time series, Time series analysis}, pages = {716--723}, file = {Akaike (1974) - A new look at the statistical model identification.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZDEZVAUN\\Akaike (1974) - A new look at the statistical model identification.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TBHVP59N\\abs_all.html:text/html} } @article{fink_cardiac_2011, series = {Cardiac {Physiome} project: {Mathematical} and {Modelling} {Foundations}}, title = {Cardiac cell modelling: {Observations} from the heart of the cardiac physiome project}, volume = {104}, issn = {0079-6107}, shorttitle = {Cardiac cell modelling}, url = {http://www.sciencedirect.com/science/article/pii/S0079610710000283}, doi = {10.1016/j.pbiomolbio.2010.03.002}, abstract = {In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field.}, number = {1–3}, urldate = {2016-05-05}, journal = {Progress in Biophysics and Molecular Biology}, author = {Fink, Martin and Niederer, Steven A. and Cherry, Elizabeth M. and Fenton, Flavio H. and Koivumäki, Jussi T. and Seemann, Gunnar and Thul, Rüdiger and Zhang, Henggui and Sachse, Frank B. and Beard, Dan and Crampin, Edmund J. and Smith, Nicolas P.}, month = jan, year = {2011}, keywords = {cardiac, Cellular, Electrophysiology, Mathematical modelling, physiome}, pages = {2--21}, file = {Fink et al (2011) - Cardiac cell modelling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\Q4XJTVT3\\Fink et al (2011) - Cardiac cell modelling.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WZMF2GKI\\S0079610710000283.html:text/html} } @article{tondel_insight_2014, title = {Insight into model mechanisms through automatic parameter fitting: a new methodological framework for model development}, volume = {8}, issn = {1752-0509}, shorttitle = {Insight into model mechanisms through automatic parameter fitting}, url = {http://www.biomedcentral.com/1752-0509/8/59}, doi = {10.1186/1752-0509-8-59}, language = {en}, number = {1}, urldate = {2016-05-05}, journal = {BMC Systems Biology}, author = {Tøndel, Kristin and Niederer, Steven A and Land, Sander and Smith, Nicolas P}, year = {2014}, pages = {59} } @article{gawthrop_modular_2015, title = {Modular {Bond}-graph {Modelling} and {Analysis} of {Biomolecular} {Systems}}, url = {http://arxiv.org/abs/1511.06482}, urldate = {2016-05-10}, journal = {arXiv preprint arXiv:1511.06482}, author = {Gawthrop, Peter and Crampin, Edmund}, year = {2015}, file = {1511.06482v1.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R4NJF8IQ\\1511.06482v1.pdf:application/pdf} } @article{okino_simplification_1998, title = {Simplification of mathematical models of chemical reaction systems}, volume = {98}, url = {http://pubs.acs.org.ezp.lib.unimelb.edu.au/doi/pdf/10.1021/cr950223l}, number = {2}, urldate = {2016-05-12}, journal = {Chemical reviews}, author = {Okino, Miles S. and Mavrovouniotis, Michael L.}, year = {1998}, pages = {391--408}, file = {Okino_Mavrovouniotis (1998) - Simplification of mathematical models of chemical reaction systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\87RQ5K3A\\Okino_Mavrovouniotis (1998) - Simplification of mathematical models of chemical reaction systems.pdf:application/pdf} } @article{faber_action_2000, title = {Action {Potential} and {Contractility} {Changes} in [{Na}$^+$]\textsubscript{i} {Overloaded} {Cardiac} {Myocytes}: {A} {Simulation} {Study}}, volume = {78}, issn = {0006-3495}, shorttitle = {Action {Potential} and {Contractility} {Changes} in [{Na}+]i {Overloaded} {Cardiac} {Myocytes}}, url = {http://www.sciencedirect.com/science/article/pii/S000634950076783X}, doi = {10.1016/S0006-3495(00)76783-X}, abstract = {Sodium overload of cardiac cells can accompany various pathologies and induce fatal cardiac arrhythmias. We investigate effects of elevated intracellular sodium on the cardiac action potential (AP) and on intracellular calcium using the Luo–Rudy model of a mammalian ventricular myocyte. The results are: 1) During rapid pacing, AP duration (APD) shortens in two phases, a rapid phase without Na+ accumulation and a slower phase that depends on [Na+]i. 2) The rapid APD shortening is due to incomplete deactivation (accumulation) of IKs. 3) The slow phase is due to increased repolarizing currents INaK and reverse-mode INaCa, secondary to elevated [Na+]i. 4) Na+-overload slows the rate of AP depolarization, allowing time for greater ICa(L) activation; it also enhances reverse-mode INaCa. The resulting increased Ca2+ influx triggers a greater [Ca2+]i transient. 5) Reverse-mode INaCa alone can trigger Ca2+ release in a voltage and [Na+]i-dependent manner. 6) During INaK block, Na+ and Ca2+ accumulate and APD shortens due to enhanced reverse-mode INaCa; contribution of IK(Na) to APD shortening is negligible. By slowing AP depolarization (hence velocity) and shortening APD, Na+-overload acts to enhance inducibility of reentrant arrhythmias. Shortened APD with elevated [Ca2+]i (secondary to Na+-overload) also predisposes the myocardium to arrhythmogenic delayed afterdepolarizations.}, number = {5}, urldate = {2016-05-23}, journal = {Biophysical Journal}, author = {Faber, Gregory M. and Rudy, Yoram}, month = may, year = {2000}, pages = {2392--2404}, file = {Faber_Rudy (2000) - Action Potential and Contractility Changes in [Na+]i Overloaded Cardiac Myocytes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MVAJZ3C4\\Faber_Rudy (2000) - Action Potential and Contractility Changes in [Na+]i Overloaded Cardiac Myocytes.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S24WBIJB\\S000634950076783X.html:text/html} } @article{qian_stoichiometric_2003, title = {Stoichiometric network theory for nonequilibrium biochemical systems}, volume = {270}, issn = {1432-1033}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1046/j.1432-1033.2003.03357.x/abstract}, doi = {10.1046/j.1432-1033.2003.03357.x}, abstract = {We introduce the basic concepts and develop a theory for nonequilibrium steady-state biochemical systems applicable to analyzing large-scale complex isothermal reaction networks. In terms of the stoichiometric matrix, we demonstrate both Kirchhoff's flux law ΣℓJℓ=0 over a biochemical species, and potential law Σℓμℓ=0 over a reaction loop. They reflect mass and energy conservation, respectively. For each reaction, its steady-state flux J can be decomposed into forward and backward one-way fluxes J = J+ – J, with chemical potential difference Δµ = RT ln(J–/J+). The product –JΔµ gives the isothermal heat dissipation rate, which is necessarily non-negative according to the second law of thermodynamics. The stoichiometric network theory (SNT) embodies all of the relevant fundamental physics. Knowing J and Δµ of a biochemical reaction, a conductance can be computed which directly reflects the level of gene expression for the particular enzyme. For sufficiently small flux a linear relationship between J and Δµ can be established as the linear flux–force relation in irreversible thermodynamics, analogous to Ohm's law in electrical circuits.}, language = {en}, number = {3}, urldate = {2016-05-23}, journal = {European Journal of Biochemistry}, author = {Qian, Hong and Beard, Daniel A. and Liang, Shou-dan}, month = feb, year = {2003}, keywords = {Biochemical network, Chemical potential, flux, Nonequilibrium thermodynamics, steady-state}, pages = {415--421}, file = {Qian et al (2003) - Stoichiometric network theory for nonequilibrium biochemical systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VK5PV7IP\\Qian et al (2003) - Stoichiometric network theory for nonequilibrium biochemical systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\35HQPUMF\\abstract.html:text/html} } @article{hartwell_molecular_1999, title = {From molecular to modular cell biology}, volume = {402}, copyright = {© 1999 Nature Publishing Group}, issn = {0028-0836}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v402/n6761supp/full/402c47a0.html?message=remove&WT.mc_id=FBK_NatureReviews}, doi = {10.1038/35011540}, abstract = {Cellular functions, such as signal transmission, are carried out by 'modules' made up of many species of interacting molecules. Understanding how modules work has depended on combining phenomenological analysis with molecular studies. General principles that govern the structure and behaviour of modules may be discovered with help from synthetic sciences such as engineering and computer science, from stronger interactions between experiment and theory in cell biology, and from an appreciation of evolutionary constraints.}, language = {en}, urldate = {2016-05-23}, journal = {Nature}, author = {Hartwell, Leland H. and Hopfield, John J. and Leibler, Stanislas and Murray, Andrew W.}, month = dec, year = {1999}, pages = {C47--C52}, file = {Hartwell et al (1999) - From molecular to modular cell biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8H27C6N4\\Hartwell et al (1999) - From molecular to modular cell biology.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DW6TS7N2\\402c47a0.html:text/html} } @article{terkildsen_balance_2007, title = {The balance between inactivation and activation of the {Na}$^+$-{K}$^+$ pump underlies the triphasic accumulation of extracellular {K}$^+$ during myocardial ischemia}, volume = {293}, copyright = {Copyright © 2007 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/293/5/H3036}, doi = {10.1152/ajpheart.00771.2007}, abstract = {Ischemia-induced hyperkalemia (accumulation of extracellular K+) predisposes the heart to the development of lethal reentrant ventricular arrhythmias. This phenomenon exhibits a triphasic time course and is thought to be mediated by a combination of three mechanisms: 1) increased cellular K+ efflux, 2) decreased cellular K+ influx, and 3) shrinkage of the extracellular space. These ischemia-induced electrophysiological changes are driven by an impaired cellular metabolism. However, the relative contributions of these mechanisms, as well as the origin of the triphasic profile, have proven to be difficult to determine experimentally. In this study, the changes in metabolite concentrations that arise during 15 min of zero-flow global ischemia were incorporated into a dynamic model of cellular electrophysiology, which was extended to include a metabolically sensitive description of the Na+-K+ pump and ATP-sensitive K+ channel, in addition to cell volume regulation. The coupling of altered K+ fluxes and cell volume regulation enables an integrative simulation of ischemic hyperkalemia. These simulations were able to quantitatively reproduce experimental measurements of the accumulation of extracellular K+ during 15 min of simulated ischemia, both with respect to the degree of K+ loss as well as the triphasic time course. Analysis of the model indicates that the inhibition of the Na+-K+ pump is the dominant factor underlying this hyperkalemic behavior, accounting for ∼85\% of the observed extracellular K+ accumulation. It was found that the balance between activation and inhibition of the Na+-K+ pump, affected by the changing metabolite and ion concentrations (in particular, [ADP]), give rise to the triphasic profile associated with ischemic hyperkalemia.}, language = {en}, number = {5}, urldate = {2016-05-23}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Terkildsen, Jonna R. and Crampin, Edmund J. and Smith, Nicolas P.}, month = nov, year = {2007}, pmid = {17873015}, pages = {H3036--H3045}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MZJCUMT5\\H3036.full.html:text/html;Terkildsen et al (2007) - The balance between inactivation and activation of the Na+-K+ pump underlies.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TDAGCV58\\Terkildsen et al (2007) - The balance between inactivation and activation of the Na+-K+ pump underlies.pdf:application/pdf} } @article{sueur_bond_1991, title = {Bond graph approach to multi-time scale systems analysis}, volume = {328}, issn = {0016-0032}, url = {http://www.sciencedirect.com/science/article/pii/001600329190066C}, doi = {10.1016/0016-0032(91)90066-C}, abstract = {The main difficulty in a problem of order reduction or simplification in modelling by decoupling different dynamics in a multi-time scale system remains the analysis to identify the slow and fast variables in the global system. Analytical (P. Kokotovic{\textgreater}, “Singular Perturbation Methods in Control. Analysis and Design”, Academic Press, London, 1986) and geometrical (G. Peponides, IEEE Trans. Circuits Systems, Vol. CAS-29, No. 11, 1982) methods have been proposed for application to a state equation model. The aim of this paper is to show up the great advantages of a bond graph model for simplification in modelling. Linear time-invariant RC networks are taken here as examples for the implementation of the study.}, number = {5}, urldate = {2016-05-24}, journal = {Journal of the Franklin Institute}, author = {Sueur, C. and Dauphin-Tanguy, G.}, month = jan, year = {1991}, pages = {1005--1026}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8QMH7XSJ\\001600329190066C.html:text/html;Sueur_Dauphin-Tanguy (1991) - Bond graph approach to multi-time scale systems analysis.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TMXTD98H\\Sueur_Dauphin-Tanguy (1991) - Bond graph approach to multi-time scale systems analysis.pdf:application/pdf} } @article{nordsletten_coupling_2011, series = {Cardiac {Physiome} project: {Mathematical} and {Modelling} {Foundations}}, title = {Coupling multi-physics models to cardiac mechanics}, volume = {104}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/S0079610709000789}, doi = {10.1016/j.pbiomolbio.2009.11.001}, abstract = {We outline and review the mathematical framework for representing mechanical deformation and contraction of the cardiac ventricles, and how this behaviour integrates with other processes crucial for understanding and modelling heart function. Building on general conservation principles of space, mass and momentum, we introduce an arbitrary Eulerian–Lagrangian framework governing the behaviour of both fluid and solid components. Exploiting the natural alignment of cardiac mechanical properties with the tissue microstructure, finite deformation measures and myocardial constitutive relations are referred to embedded structural axes. Coupling approaches for solving this large deformation mechanics framework with three dimensional fluid flow, coronary hemodynamics and electrical activation are described. We also discuss the potential of cardiac mechanics modelling for clinical applications.}, number = {1–3}, urldate = {2016-05-24}, journal = {Progress in Biophysics and Molecular Biology}, author = {Nordsletten, D. A. and Niederer, S. A. and Nash, M. P. and Hunter, P. J. and Smith, N. P.}, month = jan, year = {2011}, keywords = {Cardiac mechanics, Large deformation mechanics, Multi-physics modelling}, pages = {77--88}, file = {Nordsletten et al (2011) - Coupling multi-physics models to cardiac mechanics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\B48W28H2\\Nordsletten et al (2011) - Coupling multi-physics models to cardiac mechanics.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4SG23XGX\\S0079610709000789.html:text/html} } @article{southern_multi-scale_2008, series = {Cardiovascular {Physiome}}, title = {Multi-scale computational modelling in biology and physiology}, volume = {96}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/S0079610707000673}, doi = {10.1016/j.pbiomolbio.2007.07.019}, abstract = {Recent advances in biotechnology and the availability of ever more powerful computers have led to the formulation of increasingly complex models at all levels of biology. One of the main aims of systems biology is to couple these together to produce integrated models across multiple spatial scales and physical processes. In this review, we formulate a definition of multi-scale in terms of levels of biological organisation and describe the types of model that are found at each level. Key issues that arise in trying to formulate and solve multi-scale and multi-physics models are considered and examples of how these issues have been addressed are given for two of the more mature fields in computational biology: the molecular dynamics of ion channels and cardiac modelling. As even more complex models are developed over the coming few years, it will be necessary to develop new methods to model them (in particular in coupling across the interface between stochastic and deterministic processes) and new techniques will be required to compute their solutions efficiently on massively parallel computers. We outline how we envisage these developments occurring.}, number = {1–3}, urldate = {2016-05-24}, journal = {Progress in Biophysics and Molecular Biology}, author = {Southern, James and Pitt-Francis, Joe and Whiteley, Jonathan and Stokeley, Daniel and Kobashi, Hiromichi and Nobes, Ross and Kadooka, Yoshimasa and Gavaghan, David}, month = jan, year = {2008}, keywords = {Cardiac modelling, ion channel, Mathematical modelling, Multi-physics, multi-scale, simulation}, pages = {60--89}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7ZHKD9GI\\S0079610707000673.html:text/html;Southern et al (2008) - Multi-scale computational modelling in biology and physiology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\43ZMK6PN\\Southern et al (2008) - Multi-scale computational modelling in biology and physiology.pdf:application/pdf} } @article{broenink_20-sim_1999, title = {20-sim software for hierarchical bond-graph/block-diagram models}, volume = {7}, issn = {0928-4869}, url = {http://www.sciencedirect.com/science/article/pii/S092848699900018X}, doi = {10.1016/S0928-4869(99)00018-X}, abstract = {We discuss the modeling and simulation package 20-sim, a tool for modeling and simulation of dynamic behavior of engineering systems. Engineering systems as application domain means that we focus on systems that span multiple physical domains and the information domain. The 20-sim software is an interactive tool, where model entry and model processing are fully integrated. This means that already during model entry and editing, models can be checked on their consistency. 20-sim has its own simulator, using sophisticated numerical integration methods, taken from. internationally accepted numerical libraries. The use of 20-sim is demonstrated by an example, in which a 3-dof scara robot with controller is modeled and simulated.}, number = {5–6}, urldate = {2016-05-25}, journal = {Simulation Practice and Theory}, author = {Broenink, Jan F}, month = dec, year = {1999}, keywords = {bond graphs, Object oriented, Software}, pages = {481--492}, file = {Broenink (1999) - 20-sim software for hierarchical bond-graph-block-diagram models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VQTN5F8B\\Broenink (1999) - 20-sim software for hierarchical bond-graph-block-diagram models.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CQPE79I3\\S092848699900018X.html:text/html} } @article{apell_electrogenic_1989, title = {Electrogenic properties of the {Na},{K} pump}, volume = {110}, issn = {0022-2631, 1432-1424}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF01869466}, doi = {10.1007/BF01869466}, language = {en}, number = {2}, urldate = {2016-05-27}, journal = {The Journal of Membrane Biology}, author = {Apell, H. J.}, month = sep, year = {1989}, keywords = {Biochemistry, general, electrogenic ion pumps, Human Physiology, ion flux, Na,K-ATPase, pump current, voltage dependence}, pages = {103--114}, file = {Apell (1989) - Electrogenic properties of the Na,K pump.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9FGA6UNI\\Apell (1989) - Electrogenic properties of the Na,K pump.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4BBACZGI\\10.html:text/html} } @article{hunter_integration_2003, title = {Integration from proteins to organs: the {Physiome} {Project}}, volume = {4}, copyright = {© 2003 Nature Publishing Group}, issn = {1471-0072}, shorttitle = {Integration from proteins to organs}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrm/journal/v4/n3/abs/nrm1054.html}, doi = {10.1038/nrm1054}, abstract = {The Physiome Project will provide a framework for modelling the human body, using computational methods that incorporate biochemical, biophysical and anatomical information on cells, tissues and organs. The main project goals are to use computational modelling to analyse integrative biological function and to provide a system for hypothesis testing.}, language = {en}, number = {3}, urldate = {2016-05-27}, journal = {Nature Reviews Molecular Cell Biology}, author = {Hunter, Peter J. and Borg, Thomas K.}, month = mar, year = {2003}, pages = {237--243}, file = {Hunter_Borg (2003) - Integration from proteins to organs.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\K2C7DTT9\\Hunter_Borg (2003) - Integration from proteins to organs.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I3NCIXH6\\nrm1054.html:text/html} } @article{luo_dynamic_1994, title = {A dynamic model of the cardiac ventricular action potential. {I}. {Simulations} of ionic currents and concentration changes.}, volume = {74}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/74/6/1071}, doi = {10.1161/01.RES.74.6.1071}, abstract = {A mathematical model of the cardiac ventricular action potential is presented. In our previous work, the membrane Na+ current and K+ currents were formulated. The present article focuses on processes that regulate intracellular Ca2+ and depend on its concentration. The model presented here for the mammalian ventricular action potential is based mostly on the guinea pig ventricular cell. However, it provides the framework for modeling other types of ventricular cells with appropriate modifications made to account for species differences. The following processes are formulated: Ca2+ current through the L-type channel (ICa), the Na(+)-Ca2+ exchanger, Ca2+ release and uptake by the sarcoplasmic reticulum (SR), buffering of Ca2+ in the SR and in the myoplasm, a Ca2+ pump in the sarcolemma, the Na(+)-K+ pump, and a nonspecific Ca(2+)-activated membrane current. Activation of ICa is an order of magnitude faster than in previous models. Inactivation of ICa depends on both the membrane voltage and [Ca2+]i. SR is divided into two subcompartments, a network SR (NSR) and a junctional SR (JSR). Functionally, Ca2+ enters the NSR and translocates to the JSR following a monoexponential function. Release of Ca2+ occurs at JSR and can be triggered by two different mechanisms, Ca(2+)-induced Ca2+ release and spontaneous release. The model provides the basis for the study of arrhythmogenic activity of the single myocyte including afterdepolarizations and triggered activity. It can simulate cellular responses under different degrees of Ca2+ overload. Such simulations are presented in our accompanying article in this issue of Circulation Research.}, language = {en}, number = {6}, urldate = {2016-05-30}, journal = {Circulation Research}, author = {Luo, C. H. and Rudy, Y.}, month = jun, year = {1994}, pmid = {7514509}, pages = {1071--1096}, file = {Luo_Rudy (1994) - A dynamic model of the cardiac ventricular action potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EFJEM2DW\\Luo_Rudy (1994) - A dynamic model of the cardiac ventricular action potential.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QQAIXV22\\1071.html:text/html} } @article{terkildsen_using_2008, title = {Using {Physiome} standards to couple cellular functions for rat cardiac excitation–contraction}, volume = {93}, issn = {1469-445X}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/expphysiol.2007.041871/abstract}, doi = {10.1113/expphysiol.2007.041871}, abstract = {Scientific endeavour is reliant upon the extension and reuse of previous knowledge. The formalization of this process for computational modelling is facilitated by the use of accepted standards with which to describe and simulate models, ensuring consistency between the models and thus reducing the development and propagation of errors. CellML 1.1, an XML-based programming language, has been designed as a modelling standard which, by virtue of its import and grouping functions, facilitates model combination and reuse. Using CellML 1.1, we demonstrate the process of formalized model reuse by combining three separate models of rat cardiomyocyte function (an electrophysiology model, a model of cellular calcium dynamics and a mechanics model) which together make up the Pandit–Hinch–Niederer et al. cell model. Not only is this integrative model of rat electromechanics a useful tool for cardiac modelling but it is also an ideal framework with which to demonstrate both the power of model reuse and the challenges associated with this process. We highlight and classify a number of these issues associated with combining models and provide some suggested solutions.}, language = {en}, number = {7}, urldate = {2016-05-30}, journal = {Experimental Physiology}, author = {Terkildsen, Jonna R. and Niederer, Steven and Crampin, Edmund J. and Hunter, Peter and Smith, Nicolas P.}, month = jul, year = {2008}, pages = {919--929}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UWD6G36T\\abstract.html:text/html;Terkildsen et al (2008) - Using Physiome standards to couple cellular functions for rat cardiac.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QMAWIC6V\\Terkildsen et al (2008) - Using Physiome standards to couple cellular functions for rat cardiac.pdf:application/pdf} } @article{pandit_mathematical_2001, title = {A {Mathematical} {Model} of {Action} {Potential} {Heterogeneity} in {Adult} {Rat} {Left} {Ventricular} {Myocytes}}, volume = {81}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349501759437}, doi = {10.1016/S0006-3495(01)75943-7}, abstract = {Mathematical models were developed to reconstruct the action potentials (AP) recorded in epicardial and endocardial myocytes isolated from the adult rat left ventricle. The main goal was to obtain additional insight into the ionic mechanisms responsible for the transmural AP heterogeneity. The simulation results support the hypothesis that the smaller density and the slower reactivation kinetics of the Ca2+-independent transient outward K+ current (It) in the endocardial myocytes can account for the longer action potential duration (APD), and more prominent rate dependence in that cell type. The larger density of the Na+ current (INa) in the endocardial myocytes results in a faster upstroke (dV/dtmax). This, in addition to the smaller magnitude of It, is responsible for the larger peak overshoot of the simulated endocardial AP. The prolonged APD in the endocardial cell also leads to an enhanced amplitude of the sustained K+ current (Iss), and a larger influx of Ca2+ ions via the L-type Ca2+ current (ICaL). The latter results in an increased sarcoplasmic reticulum (SR) load, which is mainly responsible for the higher peak systolic value of the Ca2+ transient [Ca2+]i, and the resultant increase in the Na+-Ca2+ exchanger (INaCa) activity, associated with the simulated endocardial AP. In combination, these calculations provide novel, quantitative insights into the repolarization process and its naturally occurring transmural variations in the rat left ventricle.}, number = {6}, urldate = {2016-05-30}, journal = {Biophysical Journal}, author = {Pandit, Sandeep V. and Clark, Robert B. and Giles, Wayne R. and Demir, Semahat S.}, month = dec, year = {2001}, pages = {3029--3051}, file = {Pandit et al (2001) - A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EV2A7DKN\\Pandit et al (2001) - A Mathematical Model of Action Potential Heterogeneity in Adult Rat Left.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FII4VQ8N\\S0006349501759437.html:text/html} } @article{hinch_simplified_2004, title = {A {Simplified} {Local} {Control} {Model} of {Calcium}-{Induced} {Calcium} {Release} in {Cardiac} {Ventricular} {Myocytes}}, volume = {87}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349504738412}, doi = {10.1529/biophysj.104.049973}, abstract = {Calcium (Ca2+)-induced Ca2+ release (CICR) in cardiac myocytes exhibits high gain and is graded. These properties result from local control of Ca2+ release. Existing local control models of Ca2+ release in which interactions between L-Type Ca2+ channels (LCCs) and ryanodine-sensitive Ca2+ release channels (RyRs) are simulated stochastically are able to reconstruct these properties, but only at high computational cost. Here we present a general analytical approach for deriving simplified models of local control of CICR, consisting of low-dimensional systems of coupled ordinary differential equations, from these more complex local control models in which LCC-RyR interactions are simulated stochastically. The resulting model, referred to as the coupled LCC-RyR gating model, successfully reproduces a range of experimental data, including L-Type Ca2+ current in response to voltage-clamp stimuli, inactivation of LCC current with and without Ca2+ release from the sarcoplasmic reticulum, voltage-dependence of excitation-contraction coupling gain, graded release, and the force-frequency relationship. The model does so with low computational cost.}, number = {6}, urldate = {2016-05-30}, journal = {Biophysical Journal}, author = {Hinch, R. and Greenstein, J. L. and Tanskanen, A. J. and Xu, L. and Winslow, R. L.}, month = dec, year = {2004}, pages = {3723--3736}, file = {Hinch et al (2004) - A Simplified Local Control Model of Calcium-Induced Calcium Release in Cardiac.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EK8BI4WG\\Hinch et al (2004) - A Simplified Local Control Model of Calcium-Induced Calcium Release in Cardiac.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VJWXN6ZH\\S0006349504738412.html:text/html} } @article{niederer_quantitative_2006, title = {A {Quantitative} {Analysis} of {Cardiac} {Myocyte} {Relaxation}: {A} {Simulation} {Study}}, volume = {90}, issn = {0006-3495}, shorttitle = {A {Quantitative} {Analysis} of {Cardiac} {Myocyte} {Relaxation}}, url = {http://www.sciencedirect.com/science/article/pii/S000634950672358X}, doi = {10.1529/biophysj.105.069534}, abstract = {The determinants of relaxation in cardiac muscle are poorly understood, yet compromised relaxation accompanies various pathologies and impaired pump function. In this study, we develop a model of active contraction to elucidate the relative importance of the [Ca2+]i transient magnitude, the unbinding of Ca2+ from troponin C (TnC), and the length-dependence of tension and Ca2+ sensitivity on relaxation. Using the framework proposed by one of our researchers, we extensively reviewed experimental literature, to quantitatively characterize the binding of Ca2+ to TnC, the kinetics of tropomyosin, the availability of binding sites, and the kinetics of crossbridge binding after perturbations in sarcomere length. Model parameters were determined from multiple experimental results and modalities (skinned and intact preparations) and model results were validated against data from length step, caged Ca2+, isometric twitches, and the half-time to relaxation with increasing sarcomere length experiments. A factorial analysis found that the [Ca2+]i transient and the unbinding of Ca2+ from TnC were the primary determinants of relaxation, with a fivefold greater effect than that of length-dependent maximum tension and twice the effect of tension-dependent binding of Ca2+ to TnC and length-dependent Ca2+ sensitivity. The affects of the [Ca2+]i transient and the unbinding rate of Ca2+ from TnC were tightly coupled with the effect of increasing either factor, depending on the reference [Ca2+]i transient and unbinding rate.}, number = {5}, urldate = {2016-05-30}, journal = {Biophysical Journal}, author = {Niederer, S. A. and Hunter, P. J. and Smith, N. P.}, month = mar, year = {2006}, pages = {1697--1722}, file = {Niederer et al (2006) - A Quantitative Analysis of Cardiac Myocyte Relaxation.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G6VFAK55\\Niederer et al (2006) - A Quantitative Analysis of Cardiac Myocyte Relaxation.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\P57M9C9V\\S000634950672358X.html:text/html} } @article{beard_biophysical_2005, title = {A {Biophysical} {Model} of the {Mitochondrial} {Respiratory} {System} and {Oxidative} {Phosphorylation}}, volume = {1}, issn = {1553-7358}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.0010036}, doi = {10.1371/journal.pcbi.0010036}, abstract = {A computational model for the mitochondrial respiratory chain that appropriately balances mass, charge, and free energy transduction is introduced and analyzed based on a previously published set of data measured on isolated cardiac mitochondria. The basic components included in the model are the reactions at complexes I, III, and IV of the electron transport system, ATP synthesis at F 1 F 0 ATPase, substrate transporters including adenine nucleotide translocase and the phosphate–hydrogen co-transporter, and cation fluxes across the inner membrane including fluxes through the K + /H + antiporter and passive H + and K + permeation. Estimation of 16 adjustable parameter values is based on fitting model simulations to nine independent data curves. The identified model is further validated by comparison to additional datasets measured from mitochondria isolated from rat heart and liver and observed at low oxygen concentration. To obtain reasonable fits to the available data, it is necessary to incorporate inorganic-phosphate-dependent activation of the dehydrogenase activity and the electron transport system. Specifically, it is shown that a model incorporating phosphate-dependent activation of complex III is able to reasonably reproduce the observed data. The resulting validated and verified model provides a foundation for building larger and more complex systems models and investigating complex physiological and pathophysiological interactions in cardiac energetics.}, number = {4}, urldate = {2016-05-30}, journal = {PLOS Comput Biol}, author = {Beard, Daniel A.}, month = sep, year = {2005}, keywords = {Membrane potential, mitochondria, Oxidation-reduction reactions, Oxygen, Oxygen consumption, Phosphates, Protons, Simulation and modeling}, pages = {e36}, file = {Beard (2005) - A Biophysical Model of the Mitochondrial Respiratory System and Oxidative.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KPJWH8TX\\Beard (2005) - A Biophysical Model of the Mitochondrial Respiratory System and Oxidative.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EX6IERXT\\article.html:text/html} } @book{goodwin_control_2001, title = {Control system design}, volume = {240}, url = {http://caaelotel.elo.utfsm.cl/home/wp-content/uploads/Control-System-Design-SalgadoGoodwinGraebe.pdf}, urldate = {2016-05-31}, publisher = {Prentice Hall New Jersey}, author = {Goodwin, Graham Clifford and Graebe, Stefan F. and Salgado, Mario E.}, year = {2001}, file = {Control System Design (G.C. Goodwin, S.F. Graebe, M.E. Salgado).pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9WBZDW93\\Control System Design (G.C. Goodwin, S.F. Graebe, M.E. Salgado).pdf:application/pdf} } @article{gonzalez_approximate_2016, title = {Approximate bond graph models for linear singularly perturbed systems}, volume = {0}, issn = {1387-3954}, url = {http://dx.doi.org/10.1080/13873954.2016.1186100}, doi = {10.1080/13873954.2016.1186100}, abstract = {A method for obtaining approximate bond graph models for linear time invariant (LTI) Multi-Input Multi-Output (MIMO) systems with singular perturbations is presented. The basic idea of using time-scale analysis in obtaining low-order models is to decouple the slow and fast models. This is achieved by using two-stage linear transformations. Hence, a procedure to construct decoupled bond graph models based on R-fields representing each dynamic of the singularly perturbed system is proposed.When the linear transformations are applied to the system with singular perturbations, non-linear and linear equations have to be solved for separating the subsystems. In many cases, the exact solutions of these equations are complicated, but approximate solutions can be determined and approximate models can be obtained.Thus, zeroth- and first-order solutions in a bond graph approach are proposed. The key to finding the approximate solutions is to obtain the relations of the original bond graph with a predefined integral causality of the system and another bond graph called the Singularly Perturbed Bond Graph whose storage elements of the fast dynamics have derivative causality and for the slow dynamics they maintain an integral causality assignment.Finally, the proposed method is applied to an illustrative example where the simulation results show the exact solutions and zeroth- and first-order approximations.}, number = {0}, urldate = {2016-06-01}, journal = {Mathematical and Computer Modelling of Dynamical Systems}, author = {Gonzalez, Gilberto and Padilla, Aaron}, month = may, year = {2016}, pages = {1--32}, file = {Gonzalez_Padilla (2016) - Approximate bond graph models for linear singularly perturbed systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\F3IBTCXP\\Gonzalez_Padilla (2016) - Approximate bond graph models for linear singularly perturbed systems.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6T2KNN9U\\13873954.2016.html:text/html} } @article{bers_cardiac_2002, title = {Cardiac excitation–contraction coupling}, volume = {415}, copyright = {© 2002 Nature Publishing Group}, issn = {0028-0836}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v415/n6868/full/415198a.html}, doi = {10.1038/415198a}, abstract = {Of the ions involved in the intricate workings of the heart, calcium is considered perhaps the most important. It is crucial to the very process that enables the chambers of the heart to contract and relax, a process called excitation–contraction coupling. It is important to understand in quantitative detail exactly how calcium is moved around the various organelles of the myocyte in order to bring about excitation–contraction coupling if we are to understand the basic physiology of heart function. Furthermore, spatial microdomains within the cell are important in localizing the molecular players that orchestrate cardiac function.}, language = {en}, number = {6868}, urldate = {2016-06-02}, journal = {Nature}, author = {Bers, Donald M.}, month = jan, year = {2002}, pages = {198--205} } @book{nilsson_electric_2011, edition = {9th}, title = {Electric {Circuits}}, isbn = {978-0-13-705051-2}, abstract = {Designed for use in a one or two-semester Introductory Circuit Analysis or Circuit Theory Course taught in Electrical or Computer Engineering Departments. The most widely used introductory circuits textbook of the past 25 years. As this book has evolved over the years to meet the changing learing styles of students, importantly, the underlying teaching approaches and philosophies remain unchanged. The goals are: - To build an understanding of concepts and ideas explicitly in terms of previous learning - To emphasize the relationship between conceptual understanding and problem solving approaches - To provide students with a strong foundation of engineering practices.}, language = {en}, publisher = {Pearson Education}, author = {Nilsson, James William and Riedel, Susan A.}, year = {2011} } @article{cellier_hierarchical_1992, title = {Hierarchical non-linear bond graphs: a unified methodology for modeling complex physical systems}, volume = {58}, issn = {0037-5497, 1741-3133}, shorttitle = {Hierarchical non-linear bond graphs}, url = {http://sim.sagepub.com/content/58/4/230}, doi = {10.1177/003754979205800404}, abstract = {Bonds graphs have been around for a quarter of a century. While originally intended for modeling mechanical systems, they have meanwhile found widespread applications in many areas of physical system modeling. Bond graphs are a very appealing tool for modeling physical systems, because they represent the flow of power through a system. Since energy and mass are the only tradable goods in our physical universe, a bond graph model is more likely to reflect physical reality than a model derived by use of any other modeling methodology. However, bond graphs, like all graphical techniques, become unwieldy when applied to complex sys tems. Also, bond graphs were traditionally used to model predominantly linear systems. This paper introduces new concepts for modeling complex physical systems through hierarchical bond graphs which can include arbitrary non-linearities. It introduces a software tool that can be used to implement these hierarchical non-linear band graphs. Finally, a new application area for bond graphs will be discussed. It will be demonstrated how these hierarchical non-linear bond graphs can be used to model chemical reaction kinetics and chemical thermodynamics together in very general terms also farther away from equilibrium than traditional approaches would permit.}, language = {en}, number = {4}, urldate = {2016-06-06}, journal = {SIMULATION}, author = {Cellier, François E.}, month = apr, year = {1992}, keywords = {bond graphs, model design, modeling software, Physics, Thermodynamics}, pages = {230--248}, file = {Cellier (1992) - Hierarchical non-linear bond graphs.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\42QBZW9B\\Cellier (1992) - Hierarchical non-linear bond graphs.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DTBU2SRS\\230.html:text/html} } @article{ortega_product_2002, title = {Product dependence and bifunctionality compromise the ultrasensitivity of signal transduction cascades}, volume = {99}, issn = {0027-8424, 1091-6490}, url = {http://www.pnas.org/content/99/3/1170}, doi = {10.1073/pnas.022267399}, abstract = {Covalent modification cycles are ubiquitous. Theoretical studies have suggested that they serve to increase sensitivity. However, this suggestion has not been corroborated experimentally in vivo. Here, we demonstrate that the assumptions of the theoretical studies, i.e., irreversibility and absence of product inhibition, were not trivial: when the conversion reactions are close to equilibrium or saturated by their product, “zero-order” ultrasensitivity disappears. For high sensitivities to arise, not only substrate saturation (zero-order) but also high equilibrium constants and low product saturation are required. Many covalent modification cycles are catalyzed by one bifunctional ‘ambiguous’ enzyme rather than by two independent proteins. This makes high substrate concentration and low product concentration for both reactions of the cycle inconsistent; such modification cycles cannot have high responses. Defining signal strength as ratios of modified (e.g., phosphorylated) over unmodified protein, signal-to-signal response sensitivity equals 1: signal strength should remain constant along a cascade of ambiguous modification cycles. We also show that the total concentration of a signalling effector protein cannot affect the signal emanating from a modification cycle catalyzed by an ambiguous enzyme if the ratio of the two forms of the effector protein is not altered. This finding may explain the experimental result that the pivotal signal transduction protein PII plus its paralogue GlnK do not control steady-state N-signal transduction in Escherichia coli. It also rationalizes the absence of strong phenotypes for many signal-transduction proteins. Emphasis on extent of modification of these proteins is perhaps more urgent than transcriptome analysis.}, language = {en}, number = {3}, urldate = {2016-06-06}, journal = {Proceedings of the National Academy of Sciences}, author = {Ortega, Fernando and Acerenza, Luis and Westerhoff, Hans V. and Mas, Francesc and Cascante, Marta}, month = feb, year = {2002}, pmid = {11830657}, pages = {1170--1175}, file = {Ortega et al (2002) - Product dependence and bifunctionality compromise the ultrasensitivity of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7SEBCBFQ\\Ortega et al (2002) - Product dependence and bifunctionality compromise the ultrasensitivity of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HI4HG7M6\\1170.html:text/html} } @article{myung_importance_2000, title = {The {Importance} of {Complexity} in {Model} {Selection}}, volume = {44}, issn = {0022-2496}, url = {http://www.sciencedirect.com/science/article/pii/S002224969991283X}, doi = {10.1006/jmps.1999.1283}, abstract = {Model selection should be based not solely on goodness-of-fit, but must also consider model complexity. While the goal of mathematical modeling in cognitive psychology is to select one model from a set of competing models that best captures the underlying mental process, choosing the model that best fits a particular set of data will not achieve this goal. This is because a highly complex model can provide a good fit without necessarily bearing any interpretable relationship with the underlying process. It is shown that model selection based solely on the fit to observed data will result in the choice of an unnecessarily complex model that overfits the data, and thus generalizes poorly. The effect of over-fitting must be properly offset by model selection methods. An application example of selection methods using artificial data is also presented.}, number = {1}, urldate = {2016-06-06}, journal = {Journal of Mathematical Psychology}, author = {Myung, In Jae}, month = mar, year = {2000}, pages = {190--204}, file = {Myung (2000) - The Importance of Complexity in Model Selection.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G4U285XS\\Myung (2000) - The Importance of Complexity in Model Selection.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KAWJV4U2\\S002224969991283X.html:text/html} } @article{thomas_spatial_1996, title = {Spatial and temporal aspects of cellular calcium signaling.}, volume = {10}, issn = {0892-6638, 1530-6860}, url = {http://www.fasebj.org/content/10/13/1505}, abstract = {Cytosolic Ca2+ signals are often organized in complex temporal and spatial patterns, even under conditions of sustained stimulation. In this review we discuss the mechanisms and physiological significance of this behavior in nonexcitable cells, in which the primary mechanism of Ca2+ mobilization is through (1,4,5)IP3-dependent Ca2+ release from intracellular stores. Oscillations of cytosolic free Ca2+ ([Ca2+]i) are a common form of temporal organization; in the spatial domain, these [Ca2+]i oscillations may take the form of [Ca2+]i waves that propagate throughout the cell or they may be restricted to specific subcellular regions. These patterns of Ca2+ signaling result from the limited range of cytoplasmic Ca2+ diffusion and the feedback regulation of the pathways responsible for Ca2+ mobilization. In addition, the spatial organization of [Ca2+]i changes appears to depend on the strategic distribution of Ca2+ stores within the cell. One type of [Ca2+]i oscillation is baseline spiking, in which discrete [Ca2+]i spikes occur with a frequency, but not amplitude, that is determined by agonist dose. Most current evidence favors a model in which baseline [Ca2+]i spiking results from the complex interplay between [Ca2+]i and (1,4,5)IP3 in regulating the gating of (1,4,5)IP3-sensitive intracellular Ca2+ channels. Sinusoidal [Ca2+]i oscillations represent a mechanistically distinct type of temporal organization, in which agonist dose regulates the amplitude but has no effect on oscillation frequency. Sinusoidal [Ca2+]i oscillations can be explained by a negative feedback effect of protein kinase C on the generation of (1,4,5)IP3 at the level of phospholipase C or its activating G-protein. The physiological significance of [Ca2+]i oscillations and waves is becoming more established with the observation of this behavior in intact tissues and by the recognition of Ca2+-dependent processes that are adapted to respond to frequency-modulated oscillatory [Ca2+]i signals. In some cells, these [Ca2+]i signals are targeted to control processes in limited cytoplasmic domains, and in other systems [Ca2+]i waves can be propagated through gap junctions to coordinate the function of multicellular systems.}, language = {en}, number = {13}, urldate = {2016-06-07}, journal = {The FASEB Journal}, author = {Thomas, A. P. and Bird, G. S. and Hajnóczky, G. and Robb-Gaspers, L. D. and Putney, J. W.}, month = nov, year = {1996}, pmid = {8940296}, pages = {1505--1517}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TJ9RHX76\\1505.html:text/html;Thomas et al (1996) - Spatial and temporal aspects of cellular calcium signaling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UBFMEWKS\\Thomas et al (1996) - Spatial and temporal aspects of cellular calcium signaling.pdf:application/pdf} } @article{taberner_innovative_2011, title = {An innovative work-loop calorimeter for in vitro measurement of the mechanics and energetics of working cardiac trabeculae}, volume = {111}, copyright = {Copyright © 2011 the American Physiological Society}, issn = {8750-7587, 1522-1601}, url = {http://jap.physiology.org.ezp.lib.unimelb.edu.au/content/111/6/1798}, doi = {10.1152/japplphysiol.00752.2011}, abstract = {We describe a unique work-loop calorimeter with which we can measure, simultaneously, the rate of heat production and force-length work output of isolated cardiac trabeculae. The mechanics of the force-length work-loop contraction mimic those of the pressure-volume work-loops experienced by the heart. Within the measurement chamber of a flow-through microcalorimeter, a trabecula is electrically stimulated to respond, under software control, in one of three modes: fixed-end, isometric, or isotonic. In each mode, software controls the position of a linear motor, with feedback from muscle force, to adjust muscle length in the desired temporal sequence. In the case of a work-loop contraction, the software achieves seamless transitions between phases of length control (isometric contraction, isometric relaxation, and restoration of resting muscle length) and force control (isotonic shortening). The area enclosed by the resulting force-length loop represents the work done by the trabecula. The change of enthalpy expended by the muscle is given by the sum of the work term and the associated amount of evolved heat. With these simultaneous measurements, we provide the first estimation of suprabasal, net mechanical efficiency (ratio of work to change of enthalpy) of mammalian cardiac trabeculae. The maximum efficiency is at the vicinity of 12\%.}, language = {en}, number = {6}, urldate = {2016-06-07}, journal = {Journal of Applied Physiology}, author = {Taberner, Andrew J. and Han, June-Chiew and Loiselle, Denis S. and Nielsen, Paul M. F.}, month = dec, year = {2011}, pmid = {21903883}, pages = {1798--1803}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IA848CDF\\1798.html:text/html;Taberner et al (2011) - An innovative work-loop calorimeter for in vitro measurement of the mechanics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AWJVSUIP\\Taberner et al (2011) - An innovative work-loop calorimeter for in vitro measurement of the mechanics.pdf:application/pdf} } @book{berg_biochemistry_2002, edition = {5th}, title = {Biochemistry}, isbn = {978-0-7167-3051-4}, publisher = {W H Freeman}, author = {Berg, Jeremy M. and Tymoczko, John L. and Stryer, Lubert and Berg, Jeremy M. and Tymoczko, John L. and Stryer, Lubert}, year = {2002} } @article{amberg_calcium_2007, title = {Calcium sparklets regulate local and global calcium in murine arterial smooth muscle}, volume = {579}, issn = {1469-7793}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/jphysiol.2006.124420/abstract}, doi = {10.1113/jphysiol.2006.124420}, abstract = {In arterial smooth muscle, protein kinase Cα (PKCα) coerces discrete clusters of L-type Ca2+ channels to operate in a high open probability mode, resulting in subcellular domains of nearly continual Ca2+ influx called ‘persistent Ca2+ sparklets’. Our previous work suggested that steady-state Ca2+ entry into arterial myocytes, and thus global [Ca2+]i, is regulated by Ca2+ influx through clusters of L-type Ca2+ channels operating in this persistently active mode in addition to openings of solitary channels functioning in a low-activity mode. Here, we provide the first direct evidence supporting this ‘Ca2+ sparklet’ model of Ca2+ influx at a physiological membrane potential and external Ca2+ concentration. In support of this model, we found that persistent Ca2+ sparklets produced local and global elevations in [Ca2+]i. Membrane depolarization increased Ca2+ influx via low-activity and high-activity persistent Ca2+ sparklets. Our data indicate that Ca2+ entering arterial smooth muscle through persistent Ca2+ sparklets accounts for approximately 50\% of the total dihydropyridine-sensitive (i.e. L-type Ca2+ channel) Ca2+ influx at a physiologically relevant membrane potential (−40 mV) and external Ca2+ concentration (2 mm). Consistent with this, inhibition of basal PKCα-dependent persistent Ca2+ sparklets decreased [Ca2+]i by about 50\% in isolated arterial myocytes and intact pressurized arteries. Taken together, these data support the conclusion that in arterial smooth muscle steady-state Ca2+ entry and global [Ca2+]i are regulated by low-activity and PKCα-dependent high-activity persistent Ca2+ sparklets.}, language = {en}, number = {1}, urldate = {2016-06-07}, journal = {The Journal of Physiology}, author = {Amberg, Gregory C. and Navedo, Manuel F. and Nieves-Cintrón, Madeline and Molkentin, Jeffery D. and Santana, Luis F.}, month = feb, year = {2007}, pages = {187--201}, file = {Amberg et al (2007) - Calcium sparklets regulate local and global calcium in murine arterial smooth.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C43QMTW9\\Amberg et al (2007) - Calcium sparklets regulate local and global calcium in murine arterial smooth.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZK2ICS7A\\abstract.html:text/html} } @article{kholodenko_negative_2000, title = {Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades}, volume = {267}, issn = {1432-1033}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1046/j.1432-1327.2000.01197.x/abstract}, doi = {10.1046/j.1432-1327.2000.01197.x}, abstract = {Functional organization of signal transduction into protein phosphorylation cascades, such as the mitogen-activated protein kinase (MAPK) cascades, greatly enhances the sensitivity of cellular targets to external stimuli. The sensitivity increases multiplicatively with the number of cascade levels, so that a tiny change in a stimulus results in a large change in the response, the phenomenon referred to as ultrasensitivity. In a variety of cell types, the MAPK cascades are imbedded in long feedback loops, positive or negative, depending on whether the terminal kinase stimulates or inhibits the activation of the initial level. Here we demonstrate that a negative feedback loop combined with intrinsic ultrasensitivity of the MAPK cascade can bring about sustained oscillations in MAPK phosphorylation. Based on recent kinetic data on the MAPK cascades, we predict that the period of oscillations can range from minutes to hours. The phosphorylation level can vary between the base level and almost 100\% of the total protein. The oscillations of the phosphorylation cascades and slow protein diffusion in the cytoplasm can lead to intracellular waves of phospho-proteins.}, language = {en}, number = {6}, urldate = {2016-06-10}, journal = {European Journal of Biochemistry}, author = {Kholodenko, Boris N.}, month = mar, year = {2000}, keywords = {Bistability, MAPK cascades, protein phosphorylation, signal transduction, sustained oscillations}, pages = {1583--1588}, file = {Kholodenko (2000) - Negative feedback and ultrasensitivity can bring about oscillations in the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QWFUIDSD\\Kholodenko (2000) - Negative feedback and ultrasensitivity can bring about oscillations in the.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8CF3GCF9\\abstract.html:text/html} } @article{rogers_collocation-galerkin_1994, title = {A collocation-{Galerkin} finite element model of cardiac action potential propagation}, volume = {41}, issn = {0018-9294}, doi = {10.1109/10.310090}, abstract = {A new computational method was developed for modeling the effects of the geometric complexity, nonuniform muscle fiber orientation, and material inhomogeneity of the ventricular wall on cardiac impulse propagation. The method was used to solve a modification to the FitzHugh-Nagumo system of equations. The geometry, local muscle fiber orientation, and material parameters of the domain were defined using linear Lagrange or cubic Hermite finite element interpolation. Spatial variations of time-dependent excitation and recovery variables were approximated using cubic Hermite finite element interpolation, and the governing finite element equations were assembled using the collocation method. To overcome the deficiencies of conventional collocation methods on irregular domains, Galerkin equations for the no-flux boundary conditions were used instead of collocation equations for the boundary degrees-of-freedom. The resulting system was evolved using an adaptive Runge-Kutta method. Converged two-dimensional simulations of normal propagation showed that this method requires less CPU time than a traditional finite difference discretization. The model also reproduced several other physiologic phenomena known to be important in arrhythmogenesis including: Wenckebach periodicity, slowed propagation and unidirectional block due to wavefront curvature, reentry around a fixed obstacle, and spiral wave reentry. In a new result, the authors observed wavespeed variations and block due to nonuniform muscle fiber orientation. The findings suggest that the finite element method is suitable for studying normal and pathological cardiac activation and has significant advantages over existing techniques.}, number = {8}, journal = {IEEE Transactions on Biomedical Engineering}, author = {Rogers, J. M. and McCulloch, A. D.}, month = aug, year = {1994}, keywords = {Action Potentials, adaptive Runge-Kutta method, anisotropy, Arrhythmias, Cardiac, arrhythmogenesis, Assembly, bioelectric potentials, Body Surface Potential Mapping, Boundary conditions, cardiac action potential propagation, Cardiology, collocation-Galerkin finite element model, computational method, Computer simulation, CPU time, cubic Hermite interpolation, Equations, finite difference discretization, finite element analysis, Finite element methods, FitzHugh-Nagumo equations system, Galerkin equations, geometric complexity, Geometry, Heart Conduction System, Heart Ventricles, Humans, Interpolation, irregular domains, Lagrangian functions, linear Lagrange interpolation, Linear Models, Mathematical Computing, Models, Cardiovascular, Moment methods, Muscles, Myocardial Contraction, no-flux boundary conditions, nonuniform muscle fiber orientation, physiological models, Solid modeling, spatial variations, spiral wave reentry, time-dependent excitation, unidirectional block, ventricular wall material inhomogeneity, wavespeed variations, Wenckebach periodicity}, pages = {743--757}, file = {IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6MUD9MPI\\abs_all.html:text/html;Rogers_McCulloch (1994) - A collocation-Galerkin finite element model of cardiac action potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7UF2FZ86\\Rogers_McCulloch (1994) - A collocation-Galerkin finite element model of cardiac action potential.pdf:application/pdf} } @article{rabbany_pressure_1994, title = {Pressure generation in a contracting myocyte}, volume = {9}, issn = {0910-8327, 1615-2573}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/BF01746060}, doi = {10.1007/BF01746060}, abstract = {Summary The central hypothesis of this investigation is that a shortening myocyte generates a time-varying transmural pressure, or intracellular pressure. A mathematical model was formulated for a single myocyte, consisting of a fluid-filled cylindrical shell with axially arranged contractile filaments, to quantitate the fiberfluid interaction. In this model, the intracellular pressure mediates the interaction between myofilament force, cell shortening, and the mechanical properties of the sarcolemma. Shortening of myofibrils, which are embedded in the fluid-filled myocytes, deforms the myocyte, thereby altering its transmural fluid pressure. This increase in transmural pressure counteracts fiber shortening, hence constituting an internal load to shortening. The shortening of the myocyte is accompanied by thickening, due to the incompressible nature of its contents. Consequently, the overall contractile performance of the cell is integrally linked to the generation of intracellular pressure. The model manifests a positive transmural pressure during shortening, but not without shortening. The pressure in the myocyte, therefore, is not a direct function of the force generated, but rather of shortening. Intracellular pressure was measured through a fluid-filled glass micropipette (5 µ ID) employing a servo-nulling pressure transducer in a standard micropuncture technique. Measured intracellular pressure in a contracting isolated skeletal myocyte of the giant barnacle is observed to be dynamically related to shortening, but not to tension without shortening. The relation between the force of contraction, cell shortening, and intracellular pressure was assessed during both isotonic and isometric contractions. The results support the prediction that isometric, or nondeforming, contractions will not develop intracellular pressure and identify a reason for relengthening of the myocytes during relaxation.}, language = {en}, number = {4}, urldate = {2016-06-16}, journal = {Heart and Vessels}, author = {Rabbany, Sina Y. and Funai, John T. and Noordergraaf, Abraham}, year = {1994}, pages = {169--174}, file = {Rabbany et al - Pressure generation in a contracting myocyte.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QQ53ZD42\\Rabbany et al - Pressure generation in a contracting myocyte.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BVM29QSB\\BF01746060.html:text/html} } @article{wilkins_calcineurin/nfat_2004, title = {Calcineurin/{NFAT} {Coupling} {Participates} in {Pathological}, but not {Physiological}, {Cardiac} {Hypertrophy}}, volume = {94}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/94/1/110}, doi = {10.1161/01.RES.0000109415.17511.18}, abstract = {Calcineurin (PP2B) is a calcium/calmodulin-activated, serine-threonine phosphatase that transmits signals to the nucleus through the dephosphorylation and translocation of nuclear factor of activated T cell (NFAT) transcription factors. Whereas calcineurin-NFAT signaling has been implicated in regulating the hypertrophic growth of the myocardium, considerable controversy persists as to its role in maintaining versus initiating hypertrophy, its role in pathological versus physiological hypertrophy, and its role in heart failure. To address these issues, NFAT-luciferase reporter transgenic mice were generated and characterized. These mice showed robust and calcineurin-specific activation in the heart that was inhibited with cyclosporin A. In the adult heart, NFAT-luciferase activity was upregulated in a delayed, but sustained manner throughout eight weeks of pathological cardiac hypertrophy induced by pressure-overload, or more dramatically following myocardial infarction-induced heart failure. In contrast, physiological hypertrophy as produced in two separate models of exercise training failed to show significant calcineurin-NFAT coupling in the heart at multiple time points, despite measurable increases in heart to body weight ratios. Moreover, stimulation of hypertrophy with growth hormone–insulin-like growth factor-1 (GH-IGF-1) failed to activate calcineurin-NFAT signaling in the heart or in culture, despite hypertrophy, activation of Akt, and activation of p70 S6K. Calcineurin Aβ gene–targeted mice also showed a normal hypertrophic response after GH-IGF-1 infusion. Lastly, exercise- or GH-IGF-1–induced cardiac growth failed to show induction of hypertrophic marker gene expression compared with pressure-overloaded animals. Although a direct cause-and-effect relationship between NFAT-luciferase activity and pathological hypertrophy was not proven here, our results support the hypothesis that separable signaling pathways regulate pathological versus physiological hypertrophic growth of the myocardium, with calcineurin-NFAT potentially serving a regulatory role that is more specialized for maladaptive hypertrophy and heart failure.}, language = {en}, number = {1}, urldate = {2016-06-16}, journal = {Circulation Research}, author = {Wilkins, Benjamin J. and Dai, Yan-Shan and Bueno, Orlando F. and Parsons, Stephanie A. and Xu, Jian and Plank, David M. and Jones, Fred and Kimball, Thomas R. and Molkentin, Jeffery D.}, month = jan, year = {2004}, pmid = {14656927}, keywords = {calcineurin, heart failure, hypertrophy, SIGNALING, transcription}, pages = {110--118}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\34W3W86B\\110.html:text/html;Wilkins et al (2004) - Calcineurin-NFAT Coupling Participates in Pathological, but not Physiological,.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GUCJDPHF\\Wilkins et al (2004) - Calcineurin-NFAT Coupling Participates in Pathological, but not Physiological,.pdf:application/pdf} } @article{an_role_2006, title = {Role of changes in cardiac metabolism in development of diabetic cardiomyopathy}, volume = {291}, copyright = {Copyright © 2006 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/291/4/H1489}, doi = {10.1152/ajpheart.00278.2006}, abstract = {In patients with diabetes, an increased risk of symptomatic heart failure usually develops in the presence of hypertension or ischemic heart disease. However, a predisposition to heart failure might also reflect the effects of underlying abnormalities in diastolic function that can occur in asymptomatic patients with diabetes alone (termed diabetic cardiomyopathy). Evidence of cardiomyopathy has also been demonstrated in animal models of both Type 1 (streptozotocin-induced diabetes) and Type 2 diabetes (Zucker diabetic fatty rats and ob/ob or db/db mice). During insulin resistance or diabetes, the heart rapidly modifies its energy metabolism, resulting in augmented fatty acid and decreased glucose consumption. Accumulating evidence suggests that this alteration of cardiac metabolism plays an important role in the development of cardiomyopathy. Hence, a better understanding of this dysregulation in cardiac substrate utilization during insulin resistance and diabetes could provide information as to potential targets for the treatment of cardiomyopathy. This review is focused on evaluating the acute and chronic regulation and dysregulation of cardiac metabolism in normal and insulin-resistant/diabetic hearts and how these changes could contribute toward the development of cardiomyopathy.}, language = {en}, number = {4}, urldate = {2016-06-16}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {An, Ding and Rodrigues, Brian}, month = oct, year = {2006}, pmid = {16751293}, pages = {H1489--H1506}, file = {An_Rodrigues (2006) - Role of changes in cardiac metabolism in development of diabetic cardiomyopathy.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZNKIJ3RU\\An_Rodrigues (2006) - Role of changes in cardiac metabolism in development of diabetic cardiomyopathy.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IU6U8U7K\\H1489.html:text/html} } @article{catterall_structure_1993, title = {Structure and {Modulation} of {Na}+ and {Ca}2+ {Channels}}, volume = {707}, issn = {1749-6632}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/j.1749-6632.1993.tb38038.x/abstract}, doi = {10.1111/j.1749-6632.1993.tb38038.x}, language = {en}, number = {1}, urldate = {2016-06-16}, journal = {Annals of the New York Academy of Sciences}, author = {Catterall, William A.}, month = dec, year = {1993}, pages = {1--19}, file = {Catterall (1993) - Structure and Modulation of Na+ and Ca2+ Channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TT32IH88\\Catterall (1993) - Structure and Modulation of Na+ and Ca2+ Channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S2P7RV5P\\abstract.html:text/html} } @article{agliari_collective_2013, title = {Collective behaviours: from biochemical kinetics to electronic circuits}, volume = {3}, issn = {2045-2322}, shorttitle = {Collective behaviours}, url = {http://www.nature.com/articles/srep03458}, doi = {10.1038/srep03458}, urldate = {2016-06-16}, journal = {Scientific Reports}, author = {Agliari, Elena and Barra, Adriano and Burioni, Raffaella and Di Biasio, Aldo and Uguzzoni, Guido}, month = dec, year = {2013} } @article{beard_energy_2002, title = {Energy {Balance} for {Analysis} of {Complex} {Metabolic} {Networks}}, volume = {83}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349502751503}, doi = {10.1016/S0006-3495(02)75150-3}, abstract = {Predicting behavior of large-scale biochemical networks represents one of the greatest challenges of bioinformatics and computational biology. Computational tools for predicting fluxes in biochemical networks are applied in the fields of integrated and systems biology, bioinformatics, and genomics, and to aid in drug discovery and identification of potential drug targets. Approaches, such as flux balance analysis (FBA), that account for the known stoichiometry of the reaction network while avoiding implementation of detailed reaction kinetics are promising tools for the analysis of large complex networks. Here we introduce energy balance analysis (EBA)—the theory and methodology for enforcing the laws of thermodynamics in such simulations—making the results more physically realistic and revealing greater insight into the regulatory and control mechanisms operating in complex large-scale systems. We show that EBA eliminates thermodynamically infeasible results associated with FBA.}, number = {1}, urldate = {2016-06-17}, journal = {Biophysical Journal}, author = {Beard, Daniel A. and Liang, Shou-dan and Qian, Hong}, month = jul, year = {2002}, pages = {79--86}, file = {Beard et al (2002) - Energy Balance for Analysis of Complex Metabolic Networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WFIFSQJ3\\Beard et al (2002) - Energy Balance for Analysis of Complex Metabolic Networks.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QNTGPDKA\\S0006349502751503.html:text/html} } @incollection{helland_partial_2004, title = {Partial {Least} {Squares} {Regression}}, copyright = {Copyright © 2004 by John Wiley \& Sons, Inc. All rights reserved.}, isbn = {978-0-471-66719-3}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1002/0471667196.ess6004.pub2/abstract}, abstract = {Partial least squares regression was introduced as an algorithm in the early 1980s, and it has gained much popularity in chemometrics. PLSR—or PLSR1—is a regression method for collinear data, and can be seen as a competitor to principal component regression. The method makes it possible to combine prediction with a study of a joint latent structure in the x, y-variables. PLSR2 is a generalization to several dependent variables. PLSR1 can be understood from a statistical point of view via its parameter algorithm and the corresponding population model.}, language = {en}, urldate = {2016-06-20}, booktitle = {Encyclopedia of {Statistical} {Sciences}}, publisher = {John Wiley \& Sons, Inc.}, author = {Helland, Inge}, year = {2004}, keywords = {algorithm, calibration, collinearity, continuum regression, cross-validation, latent variables, loadings, model reduction, multicollinearity, population model, principal component regression, random x regression, scores}, file = {Helland (2004) - Partial Least Squares Regression.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CJETNAKK\\Helland (2004) - Partial Least Squares Regression.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PKV8D7A2\\abstract.html:text/html} } @article{waltemath_toward_2016, title = {Toward community standards and software for whole-cell modeling}, volume = {PP}, issn = {0018-9294}, doi = {10.1109/TBME.2016.2560762}, abstract = {Whole-cell (WC) modeling is a promising tool for biological research, bioengineering, and medicine. However, substantial work remains to create accurate, comprehensive models of complex cells. Methods: We organized the 2015 Whole-Cell Modeling Summer School to teach WC modeling and evaluate the need for new WC modeling standards and software by recoding a recently published WC model in SBML. Results: Our analysis revealed several challenges to representing WC models using the current standards. Conclusion: We, therefore, propose several new WC modeling standards, software, and databases. Significance:We anticipate that these new standards and software will enable more comprehensive models.}, number = {99}, journal = {IEEE Transactions on Biomedical Engineering}, author = {Waltemath, D. and Karr, J. and Bergmann, F. and Chelliah, V. and Hucka, M. and Krantz, M. and Liebermeister, W. and Mendes, P. and Myers, C. and Pir, P. and Alaybeyoglu, B. and Aranganathan, N. and Baghalian, K. and Bittig, A. and Burke, P. and Cantarelli, M. and Chew, Y. and Costa, R. and Cursons, J. and Czauderna, T. and Goldberg, A. and Gomez, H. and Hahn, J. and Hameri, T. and Gardiol, D. and Kazakiewicz, D. and Kiselev, I. and Knight-Schrijver, V. and Knupfer, C. and Konig, M. and Lee, D. and Lloret-Villas, A. and Mandrik, N. and Medley, J. and Moreau, B. and Naderi-Meshkin, H. and Palaniappan, S. and Priego-Espinosa, D. and Scharm, M. and Sharma, M. and Smallbone, K. and Stanford, N. and Song, J. H. and Theile, T. and Tokic, M. and Tomar, N. and Toure, V. and Uhlendorf, J. and Varusai, T. and Watanabe, L. and Wendland, F. and Wolfien, M. and Yurkovich, J. and Zhu, Y. and Zardilis, A. and Zhukova, A. and Schreiber, F.}, year = {2016}, keywords = {Biological system modeling, computational biology, Computational modeling, Education, Mathematical model, Optical wavelength conversion, simulation, Standards, Systems Biology, Whole-cell modeling}, pages = {1--1}, file = {IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MBF9FZK9\\abstractAuthors.html:text/html;Waltemath et al (2016) - Toward community standards and software for whole-cell modeling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WBREDNZK\\Waltemath et al (2016) - Toward community standards and software for whole-cell modeling.pdf:application/pdf} } @article{popel_systems_2009, title = {Systems {Biology} and {Physiome} {Projects}}, volume = {1}, copyright = {Copyright © 2009 John Wiley \& Sons, Inc.}, issn = {1939-005X}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1002/wsbm.67/abstract}, doi = {10.1002/wsbm.67}, abstract = {For further resources related to this article, please visit the WIREs website.}, language = {en}, number = {2}, urldate = {2016-06-22}, journal = {Wiley Interdisciplinary Reviews: Systems Biology and Medicine}, author = {Popel, Aleksander S. and Hunter, Peter J.}, month = sep, year = {2009}, pages = {153--158}, file = {Popel_Hunter (2009) - Systems Biology and Physiome Projects.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8UKS75BZ\\Popel_Hunter (2009) - Systems Biology and Physiome Projects.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FM9N6USG\\full.html:text/html} } @article{beard_multiscale_2012, title = {Multiscale {Modeling} and {Data} {Integration} in the {Virtual} {Physiological} {Rat} {Project}}, volume = {40}, issn = {0090-6964, 1573-9686}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1007/s10439-012-0611-7}, doi = {10.1007/s10439-012-0611-7}, abstract = {It has become increasingly evident that the descriptions of many complex diseases are only possible by taking into account multiple influences at different physiological scales. To do this with computational models often requires the integration of several models that have overlapping scales (genes to molecules, molecules to cells, cells to tissues). The Virtual Physiological Rat (VPR) Project, a National Institute of General Medical Sciences (NIGMS) funded National Center of Systems Biology, is tasked with mechanistically describing several complex diseases and is therefore identifying methods to facilitate the process of model integration across physiological scales. In addition, the VPR has a considerable experimental component and the resultant data must be integrated into these composite multiscale models and made available to the research community. A perspective of the current state of the art in model integration and sharing along with archiving of experimental data will be presented here in the context of multiscale physiological models. It was found that current ontological, model and data repository resources and integrative software tools are sufficient to create composite models from separate existing models and the example composite model developed here exhibits emergent behavior not predicted by the separate models.}, language = {en}, number = {11}, urldate = {2016-06-24}, journal = {Annals of Biomedical Engineering}, author = {Beard, Daniel A. and Neal, Maxwell L. and Tabesh-Saleki, Nazanin and Thompson, Christopher T. and Bassingtwaighte, James B. and Shimoyama, Mary and Carlson, Brian E.}, month = jul, year = {2012}, pages = {2365--2378}, file = {Beard et al (2012) - Multiscale Modeling and Data Integration in the Virtual Physiological Rat.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5APIUWND\\Beard et al (2012) - Multiscale Modeling and Data Integration in the Virtual Physiological Rat.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DQBGFF7Q\\s10439-012-0611-7.html:text/html} } @article{neal_semantics-based_2015, title = {Semantics-{Based} {Composition} of {Integrated} {Cardiomyocyte} {Models} {Motivated} by {Real}-{World} {Use} {Cases}}, volume = {10}, issn = {1932-6203}, url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0145621}, doi = {10.1371/journal.pone.0145621}, abstract = {Semantics-based model composition is an approach for generating complex biosimulation models from existing components that relies on capturing the biological meaning of model elements in a machine-readable fashion. This approach allows the user to work at the biological rather than computational level of abstraction and helps minimize the amount of manual effort required for model composition. To support this compositional approach, we have developed the SemGen software, and here report on SemGen’s semantics-based merging capabilities using real-world modeling use cases. We successfully reproduced a large, manually-encoded, multi-model merge: the “Pandit-Hinch-Niederer” (PHN) cardiomyocyte excitation-contraction model, previously developed using CellML. We describe our approach for annotating the three component models used in the PHN composition and for merging them at the biological level of abstraction within SemGen. We demonstrate that we were able to reproduce the original PHN model results in a semi-automated, semantics-based fashion and also rapidly generate a second, novel cardiomyocyte model composed using an alternative, independently-developed tension generation component. We discuss the time-saving features of our compositional approach in the context of these merging exercises, the limitations we encountered, and potential solutions for enhancing the approach.}, number = {12}, urldate = {2016-06-27}, journal = {PLOS ONE}, author = {Neal, Maxwell L. and Carlson, Brian E. and Thompson, Christopher T. and James, Ryan C. and Kim, Karam G. and Tran, Kenneth and Crampin, Edmund J. and Cook, Daniel L. and Gennari, John H.}, month = dec, year = {2015}, keywords = {Biophysical simulations, Biophysics, Flow rate, Gene ontologies, Intracellular membranes, Physical properties, Simulation and modeling, Troponin}, pages = {e0145621}, file = {Neal et al (2015) - Semantics-Based Composition of Integrated Cardiomyocyte Models Motivated by.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\48K4T5GG\\Neal et al (2015) - Semantics-Based Composition of Integrated Cardiomyocyte Models Motivated by.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GHAHS7PI\\article.html:text/html} } @incollection{mayer_lumbar_2011, address = {Philadelphia}, edition = {6th}, title = {Lumbar {Musculature}}, booktitle = {The {Spine}}, publisher = {Saunders Elsevier}, author = {Mayer, Tom G and Mayer, Eric A.K. and Reese, Dale}, year = {2011}, pages = {80--96} } @book{plowman_exercise_1997, address = {Boston}, title = {Exercise {Physiology} for {Health}, {Fitness}, and {Performance}}, publisher = {Allyn \& Bacon}, author = {Plowman, S.A. and Smith, D.L.}, year = {1997} } @article{vinnakota_myocardial_2004, title = {Myocardial density and composition: a basis for calculating intracellular metabolite concentrations}, volume = {286}, copyright = {Copyright © 2004 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, shorttitle = {Myocardial density and composition}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/286/5/H1742}, doi = {10.1152/ajpheart.00478.2003}, abstract = {Systems for describing myocardial cellular metabolism with appropriate thermodynamic constraints on reactions have to be on the basis of estimates of intracellular and mitochondrial concentrations of metabolites as driving forces for reactions. This requires that tissue composition itself must be modeled, but there is marked inconsistency in the literature and no full data set on hearts of any species. To formulate a self-consistent set of information on the densities, contents, or concentrations of chemical components and volumes of tissue spaces, we drew on information mostly on rats. From the data on densities, volumes, volume fractions, and mass fractions observed mainly on left ventricular myocardium, cytoplasm, and mitochondria and from morphometric data on cellular components and the vasculature, we constructed a matrix based on conservation laws for density, volume, and constituent composition. The four constituents were water, protein, fat, and solutes (or ash). To take into account the variances in the observed data sets, we used a constrained nonlinear least squares optimization to minimize the differences between the final results and the data sets. The results provide a detailed estimate of cardiac tissue composition, previously unavailable, for the translation of whole tissue concentrations or concentrations per gram protein into estimated local concentrations that are relevant to reaction processes. An example is that the concentrations of phosphocreatine and ATP in cytosolic water space are twice as high as their mean tissue concentrations. This conservation optimization method is applicable to any tissue or organ.}, language = {en}, number = {5}, urldate = {2016-07-08}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Vinnakota, Kalyan C. and Bassingthwaighte, James B.}, month = may, year = {2004}, pmid = {14693681}, pages = {H1742--H1749}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\Z2CB8E3V\\H1742.html:text/html;Vinnakota_Bassingthwaighte (2004) - Myocardial density and composition.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DB26GF64\\Vinnakota_Bassingthwaighte (2004) - Myocardial density and composition.pdf:application/pdf} } @article{voit_150_2015, title = {150 {Years} of the {Mass} {Action} {Law}}, volume = {11}, issn = {1553-7358}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1004012}, doi = {10.1371/journal.pcbi.1004012}, abstract = {This year we celebrate the 150th anniversary of the law of mass action. This law is often assumed to have been “there” forever, but it has its own history, background, and a definite starting point. The law has had an impact on chemistry, biochemistry, biomathematics, and systems biology that is difficult to overestimate. It is easily recognized that it is the direct basis for computational enzyme kinetics, ecological systems models, and models for the spread of diseases. The article reviews the explicit and implicit role of the law of mass action in systems biology and reveals how the original, more general formulation of the law emerged one hundred years later ab initio as a very general, canonical representation of biological processes.}, number = {1}, urldate = {2016-07-11}, journal = {PLOS Comput Biol}, author = {Voit, Eberhard O. and Martens, Harald A. and Omholt, Stig W.}, month = jan, year = {2015}, keywords = {Biochemistry, Chemical biology, Chemical reactions, Chemists, computational biology, Differential equations, Mathematical models, Systems Biology}, pages = {e1004012}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QCCAUBMF\\article.html:text/html;Voit et al (2015) - 150 Years of the Mass Action Law.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TNNW6WPM\\Voit et al (2015) - 150 Years of the Mass Action Law.pdf:application/pdf} } @book{koudriavtsev_law_2001, address = {Berlin, Heidelberg}, title = {The {Law} of {Mass} {Action}}, isbn = {978-3-642-62494-0 978-3-642-56770-4}, url = {http://link.springer.com/10.1007/978-3-642-56770-4}, language = {en}, urldate = {2016-07-11}, publisher = {Springer Berlin Heidelberg}, author = {Koudriavtsev, Andrei and Jameson, Reginald F. and Linert, Wolfgang}, year = {2001}, file = {Koudriavtsev et al. - 2001 - The Law of Mass Action.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9SCDA5JC\\Koudriavtsev et al. - 2001 - The Law of Mass Action.pdf:application/pdf} } @article{peachey_sarcoplasmic_1965, title = {The {Sarcoplasmic} {Reticulum} and {Transverse} {Tubules} of the {Frog}'s {Sartorius}}, volume = {25}, issn = {0021-9525, 1540-8140}, url = {http://jcb.rupress.org.ezp.lib.unimelb.edu.au/content/25/3/209}, doi = {10.1083/jcb.25.3.209}, abstract = {The sarcoplasmic reticulum of the frog's sartorius muscle was examined by electron microscopy following sequential fixation in glutaraldehyde and osmium tetroxide and embedding in Epon. The earlier results of Porter and Palade on Ambystoma muscle were confirmed in the sartorius. In addition, the transverse tubules were observed to be continuous across the width of the fiber, a set of flat intermediate cisternae was seen to connect the terminal cisternae to the longitudinal tubules in the A band, and the continuous reticulum collar at the center of the A band was found to be perforated by circular and elongated pores (the fenestrated collar). The transverse tubules have a volume about 0.3 per cent of the fiber volume, and a surface area about 7 times the outer cylindrical surface area for a fiber 100 µ in diameter. The terminal cisternae, the intermediate cisternae, and the longitudinal tubules together with the fenestrated collar each have a volume of 4 to 5 per cent of the fiber volume and a surface area 40 to 50 times the outer surface area of a fiber 100 µ in diameter. Some evidence for continuity of the transverse tubules with the fiber surface is presented, but this is thought to be not so convincing as evidence presented by others. The results are discussed in terms of a possible mechanism for a role of the transverse tubules and sarcoplasmic reticulum in excitation-contraction coupling, as suggested by their morphology and a variety of physiological studies. In this scheme, the transverse tubules are thought to be electrically coupled to the terminal cisternae, so that depolarization of the fiber surface spreads inward along the transverse tubules and to the terminal cisternae, initiating the release of a contraction-activating substance.}, language = {en}, number = {3}, urldate = {2016-07-11}, journal = {The Journal of Cell Biology}, author = {Peachey, Lee D.}, month = jun, year = {1965}, pmid = {5840799}, pages = {209--231}, file = {Peachey (1965) - The Sarcoplasmic Reticulum and Transverse Tubules of the Frog's Sartorius.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7U3Q62V6\\Peachey (1965) - The Sarcoplasmic Reticulum and Transverse Tubules of the Frog's Sartorius.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\H5CFWT8F\\209.html:text/html} } @article{hund_ionic_2001, title = {Ionic {Charge} {Conservation} and {Long}-{Term} {Steady} {State} in the {Luo}–{Rudy} {Dynamic} {Cell} {Model}}, volume = {81}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349501759656}, doi = {10.1016/S0006-3495(01)75965-6}, abstract = {It has been postulated that cardiac cell models accounting for changes in intracellular ion concentrations violate a conservation principle, and, as a result, computed parameters (e.g., ion concentrations and transmembrane potential, Vm) drift in time, never attaining steady state. To address this issue, models have been proposed that invoke the charge conservation principle to calculate Vm from ion concentrations (“algebraic” method), rather than from transmembrane current (“differential” method). The aims of this study are to compare model behavior during prolonged periods of pacing using the algebraic and differential methods, and to address the issue of model drift. We pace the Luo–Rudy dynamic model of a cardiac ventricular cell and compare the time-dependent behavior of computed parameters using the algebraic and differential methods. When ions carried by the stimulus current are taken into account, the algebraic and differential methods yield identical results and neither shows drift in computed parameters. The present study establishes the proper pacing protocol for simulation studies of cellular behavior during long periods of rapid pacing. Such studies are essential for mechanistic understanding of arrhythmogenesis, since cells are subjected to rapid periodic stimulation during many arrhythmias.}, number = {6}, urldate = {2016-08-04}, journal = {Biophysical Journal}, author = {Hund, Thomas J. and Kucera, Jan P. and Otani, Niels F. and Rudy, Yoram}, month = dec, year = {2001}, pages = {3324--3331}, file = {Hund et al (2001) - Ionic Charge Conservation and Long-Term Steady State in the Luo–Rudy Dynamic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UR8RRH8Q\\Hund et al (2001) - Ionic Charge Conservation and Long-Term Steady State in the Luo–Rudy Dynamic.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MNHHHIJ8\\S0006349501759656.html:text/html} } @article{beaman_constitutive_1988, title = {Constitutive and {Modulation} {Structure} in {Bond} {Graph} {Modeling}}, volume = {110}, issn = {0022-0434}, url = {http://dx.doi.org/10.1115/1.3152702}, doi = {10.1115/1.3152702}, abstract = {In this paper, we investigate additional structure that might be put on bond graphs in order that (1) a bond graph has a physical realization and (2) physical realizations have bond graph within an appropriate physical domain. In particular, restrictions are proposed on the allowed form for the constitutive laws for energy storing and dissipative elements and the allowed form for the modulation of coupling elements. This added structure is proposed to ensure the existence of an energy state function, passivity, unique solutions to the model equations, and to preserve the signal nature of modulation.}, number = {4}, urldate = {2016-08-19}, journal = {Journal of Dynamic Systems, Measurement, and Control}, author = {Beaman, J. J. and Rosenberg, R. C.}, month = dec, year = {1988}, pages = {395--402}, file = {Beaman_Rosenberg (1988) - Constitutive and Modulation Structure in Bond Graph Modeling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TQVSXKRR\\Beaman_Rosenberg (1988) - Constitutive and Modulation Structure in Bond Graph Modeling.pdf:application/pdf} } @article{pfeiffer_metatool:_1999, title = {{METATOOL}: for studying metabolic networks.}, volume = {15}, issn = {1367-4803, 1460-2059}, shorttitle = {{METATOOL}}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/15/3/251}, doi = {10.1093/bioinformatics/15.3.251}, abstract = {MOTIVATION: To reconstruct metabolic pathways from biochemical and/or genome sequence data, the stoichiometric and thermodynamic feasibility of the pathways has to be tested. This is achieved by characterizing the admissible region of flux distributions in steady state. This region is spanned by what can be called a convex basis. The concept of 'elementary flux modes' provides a mathematical tool to define all metabolic routes that are feasible in a given metabolic network. In addition, we define 'enzyme subsets' to be groups of enzymes that operate together in fixed flux proportions in all steady states of the system. RESULTS: Algorithms for computing the convex basis and elementary modes developed earlier are briefly reviewed. A newly developed algorithm for detecting all enzyme subsets in a given network is presented. All of these algorithms have been implemented in a novel computer program named METATOOL, whose features are outlined here. The algorithms are illustrated by an example taken from sugar metabolism. AVAILABILITY: METATOOL is available from ftp://bmsdarwin.brookes.ac. uk/pub/software/ibmpc/metatool. SUPPLEMENTARY INFORMATION: http://www. biologie.hu-berlin.de/biophysics/Theory/tpfeiffer/metatoo l.html}, language = {en}, number = {3}, urldate = {2016-08-22}, journal = {Bioinformatics}, author = {Pfeiffer, T. and S√°nchez-Valdenebro, I. and Nu√±o, J. C. and Montero, F. and Schuster, S.}, month = mar, year = {1999}, pmid = {10222413}, pages = {251--257}, file = {Pfeiffer et al (1999) - METATOOL.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3KMF2A9Z\\Pfeiffer et al (1999) - METATOOL.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2B3SUWEI\\251.html:text/html} } @article{surovtsova_simplification_2012, title = {Simplification of biochemical models: a general approach based on the analysis of the impact of individual species and reactions on the systems dynamics}, volume = {6}, issn = {1752-0509}, shorttitle = {Simplification of biochemical models}, url = {http://bmcsystbiol.biomedcentral.com/articles/10.1186/1752-0509-6-14}, doi = {10.1186/1752-0509-6-14}, language = {en}, number = {1}, urldate = {2016-08-29}, journal = {BMC Systems Biology}, author = {Surovtsova, Irina and Simus, Natalia and Hübner, Katrin and Sahle, Sven and Kummer, Ursula}, year = {2012}, pages = {14}, file = {Surovtsova et al (2012) - Simplification of biochemical models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8P4V7GX2\\Surovtsova et al (2012) - Simplification of biochemical models.pdf:application/pdf} } @article{alberty_rapid-equilibrium_2008, title = {Rapid-{Equilibrium} {Enzyme} {Kinetics}}, volume = {85}, issn = {0021-9584}, url = {http://dx.doi.org/10.1021/ed085p1136}, doi = {10.1021/ed085p1136}, abstract = {Rapid-equilibrium rate equations for enzyme-catalyzed reactions are especially useful because if experimental data can be fit by these simpler rate equations, the Michaelis constants can be interpreted as equilibrium constants. However, for some reactions it is necessary to use the more complicated steady-state rate equations. Thermodynamics is used in rapid-equilibrium derivations to calculate the equilibrium concentrations of reactants up to the rate-determining reaction, and that means that the reactions in the mechanism have to be independent. This is quite different from steady-state treatments of mechanisms where reactions do not have to be independent. The innovation in this article is the use of half-reactions to construct complete rapid-equilibrium rate equations. Five half-reactions are described. Any forward half-reaction can be combined with any reverse half-reaction. Rapid-equilibrium rate equations are given for fifteen mechanisms of enzyme-catalyzed reactions, but more rate equations can be constructed from these five half-reactions.}, number = {8}, urldate = {2016-09-06}, journal = {Journal of Chemical Education}, author = {Alberty, Robert A.}, month = aug, year = {2008}, pages = {1136}, file = {ACS Full Text Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TX9QCPQH\\ed085p1136.html:text/html;Alberty (2008) - Rapid-Equilibrium Enzyme Kinetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8I9T3NTD\\Alberty (2008) - Rapid-Equilibrium Enzyme Kinetics.pdf:application/pdf} } @article{schauer_quasi-steady-state_1983, title = {Quasi-steady-state approximation in the mathematical modeling of biochemical reaction networks}, volume = {65}, issn = {0025-5564}, url = {http://www.sciencedirect.com/science/article/pii/0025556483900585}, doi = {10.1016/0025-5564(83)90058-5}, abstract = {In the mathematical modeling of biochemical reaction networks the application of the quasi-steady-state approximation permits a reduction of the number of dynamic variables as well as of the number of parameters. It is shown that the quasi-steady-state approximation represents the zeroth approximate solution of the perturbation problemdXdt = RV(X)+1μSW̃(X) with μ ⪡ 1. The perturbation equation develops by subdivision of the flux rates of the model into the rates wi(X) = (1/μ)w̃i(X) of fast reactions and the rates vj(X) of slow reactions. The matrix C=(R⋮S) denotes the stochiometric matrix of the reaction network. The analysis of this perturbation problem provides conditions for the applicability of the quasi-steady-state approximation in a given network. The paper presents a practical guide for the construction of the approximate solution.}, number = {2}, urldate = {2016-09-07}, journal = {Mathematical Biosciences}, author = {Schauer, M. and Heinrich, R.}, month = aug, year = {1983}, pages = {155--170}, file = {Schauer_Heinrich (1983) - Quasi-steady-state approximation in the mathematical modeling of biochemical.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\X7Z8E4B7\\Schauer_Heinrich (1983) - Quasi-steady-state approximation in the mathematical modeling of biochemical.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\K5BCHNGF\\0025556483900585.html:text/html} } @article{gold_kinetic_1970, title = {Kinetic {Mechanism} of {Rabbit} {Muscle} {Glycogen} {Phosphorylase} a}, volume = {245}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/245/10/2564}, abstract = {Isotope-exchange rates at chemical equilibrium were determined for the glycogen-α-d-glucopyranose 1-phosphate-Pi system in the presence of phosphorylase a. Exchange of 32P from α-d-glycopyranose 1-phosphate (glucose-1-P) into Pi and exchange of 14C from glucose-1-P into glycogen were followed simultaneously by the use of glucose-1-P containing both isotopes. Concentrations of glucose-1-P and Pi were varied together in their equilibrium ratio at constant glycogen concentration, and the concentration of glycogen was varied at fixed concentrations of phosphates. Exchange rates for the two isotopes were equal under all conditions (with the possible exception of measurements at the highest concentrations of the phosphates) and gave linear reciprocal plots. One exception was noted in which the reciprocal plot was concave upward at low concentrations of substrate, probably because of allosteric effects. The results support a rapid equilibrium mechanism. Initial velocity of the reaction in the absence of product was determined by the use of an isotopic assay. The results were characteristic of a sequential mechanism. Isotope-exchange rates were also determined under nonequilibrium conditions. Exchange of 32P from glucose-1-P into Pi was followed as a function of glycogen concentration at a fixed concentration of glucose-1-P and several fixed concentrations of Pi. The exchange was also followed as a function of glucose-1-P concentration at fixed glycogen concentration and several fixed Pi concentrations. Similar experiments were done while following the exchange from Pi into glucose-1-P. These experiments are equivalent to conventional product inhibition experiments. The results indicate that the two phosphates are noncompetitive inhibitors with respect to glycogen, but are competitive with respect to one another. Our conclusion is that phosphorylase a has a rapid equilibrium Random Bi-Bi mechanism involving binary complexes of enzyme with glycogen, glucose-1-P, and Pi, and ternary complexes of enzyme with glycogen and glucose-1-P and with glycogen and Pi.}, language = {en}, number = {10}, urldate = {2016-09-14}, journal = {Journal of Biological Chemistry}, author = {Gold, Allen M. and Johnson, Robert M. and Tseng, John K.}, month = may, year = {1970}, pmid = {5445800}, pages = {2564--2572}, file = {Gold et al (1970) - Kinetic Mechanism of Rabbit Muscle Glycogen Phosphorylase a.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FTN8QI6M\\Gold et al (1970) - Kinetic Mechanism of Rabbit Muscle Glycogen Phosphorylase a.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HBA4JMA4\\2564.html:text/html} } @article{schuster_rapid-equilibrium_1994, title = {Rapid-equilibrium {Approximation} applied to mathematical models of {Tracer} dynamics in biochemical reaction systems}, volume = {19}, issn = {0895-7177}, url = {http://www.sciencedirect.com/science/article/pii/0895717794901961}, doi = {10.1016/0895-7177(94)90196-1}, abstract = {A method is presented which allows to reduce the size of the differential equation system describing the dynamics of radioactive tracers in biochemical reaction systems endowed with time hierarchy, i.e., encompassing fast and slow reaction rates which may differ by several orders of magnitude. The basic idea of this approach is to apply the rapid-equilibrium approximation commonly used in the mathematical modelling of metabolic systems (cf. [1] for lumping into single “pool variables” all those reactive groups which can be labeled and which are connected by fast reversible reactions. The set of remaining slow reactions governing the dynamics of the reduced system of pool variables depends on the special way of labeling chosen. Thus, the reduction procedure permits to judge the maximal possible number of flux rates which can be estimated from stationary or time-dependent tracer experiments by regression analysis (fitting). Moreover, the method can be employed for identifying near-equilibrium and nonequilibrium reactions. An illustration of the reduction algorithm is provided by considering the distribution of 14C-tracers in the pentose phosphate pathway.}, number = {6}, urldate = {2016-09-16}, journal = {Mathematical and Computer Modelling}, author = {Schuster, R. and Holzhütter, H. -G.}, month = mar, year = {1994}, pages = {241--253}, file = {Schuster_Holzhütter (1994) - Rapid-equilibrium Approximation applied to mathematical models of Tracer.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5PR2AK4A\\Schuster_Holzhütter (1994) - Rapid-equilibrium Approximation applied to mathematical models of Tracer.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DQ4B2XGJ\\0895717794901961.html:text/html} } @article{smith_sarcomere_nodate, title = {From sarcomere to cell: {An} efficient algorithm for linking mathematical models of muscle contraction}, volume = {65}, issn = {0092-8240, 1522-9602}, shorttitle = {From sarcomere to cell}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1016/S0092-8240(03)00063-6}, doi = {10.1016/S0092-8240(03)00063-6}, abstract = {Two classes of mathematical framework have previously been developed to model active tension generation in contracting muscle. Cross-bridge models of muscle are biophysically based but computationally expensive to solve, and thus unsuitable for embedding in spatially distributed continuum representations. Fading memory models are computationally efficient but provide limited biophysical insight. In this study a novel computational method is proposed for coupling these two frameworks such that biophysical events can be determined and computational tractability maintained. Within the cross-bridge model, the functional forms of the distribution of cross-bridges, as a function of strain in each state, are approximated using the distribution moment approach. Using the variables of area, mean and standard deviation of each distribution, analytic expressions are developed to calculate the temporal dynamics of stiffness, tension and energy. A root finding method is employed to adjust the variables such that the temporal dynamics of the cross-bridge model match those of an equivalent fading memory model. The method is demonstrated for sinusoidal perturbations in length at two frequencies, with an approximate 30-fold increase in computational efficiency over a conventional technique for finding a solution to the cross-bridge model.}, language = {en}, number = {6}, urldate = {2016-09-19}, journal = {Bulletin of Mathematical Biology}, author = {Smith, Nicolas P.}, pages = {1141--1162}, file = {Full Text PDF:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\53QK5NGI\\Smith - From sarcomere to cell An efficient algorithm for.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QZBTXZ5J\\10.html:text/html} } @article{nakao_[na]_1989, title = {[{Na}] and [{K}] dependence of the {Na}/{K} pump current-voltage relationship in guinea pig ventricular myocytes.}, volume = {94}, copyright = {© 1989 Rockefeller University Press}, issn = {0022-1295, 1540-7748}, url = {http://jgp.rupress.org.ezp.lib.unimelb.edu.au/content/94/3/539}, doi = {10.1085/jgp.94.3.539}, abstract = {Na/K pump current was determined between -140 and +60 mV as steady-state, strophanthidin-sensitive, whole-cell current in guinea pig ventricular myocytes, voltage-clamped and internally dialyzed via wide-tipped pipettes. Solutions were designed to minimize all other components of membrane current. A device for exchanging the solution inside the pipette permitted investigation of Na/K pump current-voltage (I-V) relationships at several levels of pipette [Na] [( Na]pip) in a single cell; the effects of changes in external [Na] [( Na]o) or external [K] [( K]o) were also studied. At 50 mM [Na]pip, 5.4 mM [K]o, and approximately 150 mM [Na]o, Na/K pump current was steeply voltage dependent at negative potentials but was approximately constant at positive potentials. Under those conditions, reduction of [Na]o enhanced pump current at negative potentials but had little effect at positive potentials: at zero [Na]o, pump current was only weakly voltage dependent. At 5.4 mM [K]o and approximately 150 mM [Na]o, reduction of [Na]pip from 50 mM scaled down the sigmoid pump I-V relationship and shifted it slightly to the right (toward more positive potentials). Pump current at 0 mV was activated by [Na]pip according to the Hill equation with best-fit K0.5 approximately equal to 11 mM and Hill coefficient nH approximately equal to 1.4. At zero [Na]o, reduction of [Na]pip seemed to simply scale down the relatively flat pump I-V relationship: Hill fit parameters for pump activation by [Na]pip at 0 mV were K0.5 approximately equal to 10 mM, nH approximately equal to 1.4. At 50 mM [Na]pip and high [Na]o, reduction of [K]o from 5.4 mM scaled down the sigmoid I-V relationship and shifted it slightly to the right: at 0 mV, K0.5 approximately equal to 1.5 mM and nH approximately equal to 1.0. At zero [Na]o, lowering [K]o simply scaled down the flat pump I-V relationships yielding, at 0 mV, K0.5 approximately equal to 0.2 mM, nH approximately equal to 1.1. The voltage-independent activation of Na/K pump current by both intracellular Na ions and extracellular K ions, at zero [Na]o, suggests that neither ion binds within the membrane field. Extracellular Na ions, however, seem to have both a voltage-dependent and a voltage-independent influence on the Na/K pump: they inhibit outward Na/K pump current in a strongly voltage-dependent fashion, with higher apparent affinity at more negative potentials (K0.5 approximately equal to 90 mM at -120 mV, and approximately 170 mM at -80 mV), and they compete with extracellular K ions in a seemingly voltage-independent manner.(ABSTRACT TRUNCATED AT 400 WORDS)}, language = {en}, number = {3}, urldate = {2016-09-21}, journal = {The Journal of General Physiology}, author = {Nakao, M. and Gadsby, D. C.}, month = sep, year = {1989}, pmid = {2607334}, pages = {539--565}, file = {Nakao_Gadsby (1989) - [Na] and [K] dependence of the Na-K pump current-voltage relationship in guinea.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SZ7TKTP7\\Nakao_Gadsby (1989) - [Na] and [K] dependence of the Na-K pump current-voltage relationship in guinea.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3VEK8EUZ\\539.html:text/html} } @article{boggs_sequential_1995, title = {Sequential {Quadratic} {Programming}}, volume = {4}, issn = {0962-4929, 1474-0508}, url = {http://www.journals.cambridge.org/abstract_S0962492900002518}, doi = {10.1017/S0962492900002518}, language = {en}, urldate = {2016-09-21}, journal = {Acta Numerica}, author = {Boggs, Paul T. and Tolle, Jon W.}, month = jan, year = {1995}, pages = {1} } @article{hansen_dependence_2002, title = {Dependence of {Na}$^+$-{K}$^+$ pump current-voltage relationship on intracellular {Na}$^+$, {K}$^+$, and {Cs}$^+$ in rabbit cardiac myocytes}, volume = {283}, copyright = {Copyright © 2002 the American Physiological Society}, issn = {0363-6143, 1522-1563}, url = {http://ajpcell.physiology.org.ezp.lib.unimelb.edu.au/content/283/5/C1511}, doi = {10.1152/ajpcell.01343.2000}, abstract = {To examine effects of cytosolic Na+, K+, and Cs+ on the voltage dependence of the Na+-K+ pump, we measured Na+-K+ pump current (I p) of ventricular myocytes voltage-clamped at potentials (V m) from −100 to +60 mV. Superfusates were designed to eliminate voltage dependence at extracellular pump sites. The cytosolic compartment of myocytes was perfused with patch pipette solutions with a Na+ concentration ([Na]pip) of 80 mM and a K+ concentration from 0 to 80 mM or with solutions containing Na+ in concentrations from 0.1 to 100 mM and K+ in a concentration of either 0 or 80 mM. When [Na]pip was 80 mM, K+ in pipette solutions had a voltage-dependent inhibitory effect on I pand induced a negative slope of theI p-V m relationship. Cs+ in pipette solutions had an effect onI p qualitatively similar to that of K+. Increases in I p with increases in [Na]pip were voltage dependent. The dielectric coefficient derived from [Na]pip-I p relationships at the different test potentials was 0.15 when pipette solutions included 80 mM K+ and 0.06 when pipette solutions were K+free.}, language = {en}, number = {5}, urldate = {2016-09-23}, journal = {American Journal of Physiology - Cell Physiology}, author = {Hansen, Peter S. and Buhagiar, Kerrie A. and Kong, Benjamin Y. and Clarke, Ronald J. and Gray, David F. and Rasmussen, Helge H.}, month = nov, year = {2002}, pmid = {12372812}, pages = {C1511--C1521}, file = {Hansen et al (2002) - Dependence of Na+-K+ pump current-voltage relationship on intracellular Na+,.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\66ZH2MVK\\Hansen et al (2002) - Dependence of Na+-K+ pump current-voltage relationship on intracellular Na+,.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DE59HDQC\\C1511.html:text/html} } @article{friedrich_na+k+-atpase_1996, title = {Na$^+$,{K}$^+$-{ATPase} pump currents in giant excised patches activated by an {ATP} concentration jump}, volume = {71}, issn = {00063495}, url = {http://linkinghub.elsevier.com/retrieve/pii/S0006349596794420}, doi = {10.1016/S0006-3495(96)79442-0}, language = {en}, number = {5}, urldate = {2016-09-26}, journal = {Biophysical Journal}, author = {Friedrich, T. and Bamberg, E. and Nagel, G.}, month = nov, year = {1996}, pages = {2486--2500}, file = {Friedrich et al (1996) - Na+,K(+)-ATPase pump currents in giant excised patches activated by an ATP.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JKMZZU9M\\Friedrich et al (1996) - Na+,K(+)-ATPase pump currents in giant excised patches activated by an ATP.pdf:application/pdf} } @article{cha_simple_1968, title = {A {Simple} {Method} for {Derivation} of {Rate} {Equations} for {Enzyme}-catalyzed {Reactions} under the {Rapid} {Equilibrium} {Assumption} or {Combined} {Assumptions} of {Equilibrium} and {Steady} {State}}, volume = {243}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/243/4/820}, abstract = {A method is described by which rate equations for enzymic reactions under the equilibrium assumptions may be derived by inspecting the reaction pathways without solving simultaneous equations in the conventional way. Also described is a simple graphic method which combines the above technique with King and Altman's method. By the latter method, rate equations may be derived with minimal effort for complicated enzymic mechanisms in which some steps are considerably faster than the rest so that the enzymic species connected by those rapid steps may be at a near equilibrium while the over-all reaction is in a steady state. Rate equations are derived, for the purpose of illustration, for the reversible single substrate-single modifier system, the partial equilibrium ping-pong bi-bi mechanism, the general mechanism for two-substrate system, and a complicated three-substrate mechanism.}, language = {en}, number = {4}, urldate = {2016-09-27}, journal = {Journal of Biological Chemistry}, author = {Cha, Sungman}, month = feb, year = {1968}, pmid = {5638598}, pages = {820--825}, file = {Cha (1968) - A Simple Method for Derivation of Rate Equations for Enzyme-catalyzed Reactions.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\X4GZ9J8G\\Cha (1968) - A Simple Method for Derivation of Rate Equations for Enzyme-catalyzed Reactions.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2SNIUBEI\\820.html:text/html} } @article{volkenstein_new_1966, title = {A new method for solving the problems of the stationary kinetics of enzymological reactions}, volume = {115}, issn = {0304-4165}, url = {http://www.sciencedirect.com/science/article/pii/0304416566904454}, doi = {10.1016/0304-4165(66)90445-4}, abstract = {A new method is proposed for solving problems of the stationary kinetics of enzymological reactions. The topological theory of graphs, which has been applied to information theory and to the theory of electrical networks etc., isapplied for the first time to biochemical kinetics. The method is illustrated by the solving of simple problems—competitive and non-competitive inhibition and the cooperative interaction of two active sites. A comparison of the method with that of King and Altman5 shows the advantages of the new algorythm.}, number = {2}, urldate = {2016-09-27}, journal = {Biochimica et Biophysica Acta (BBA) - General Subjects}, author = {Volkenstein, M. V. and Goldstein, B. N.}, month = feb, year = {1966}, pages = {471--477}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UDQUI7EA\\0304416566904454.html:text/html} } @article{vrzheshch_accuracy_2015, title = {The accuracy of rapid equilibrium assumption in steady-state enzyme kinetics is a function of equilibrium segment structure and properties}, volume = {60}, issn = {0006-3509, 1555-6654}, url = {http://link.springer.com.ezp.lib.unimelb.edu.au/article/10.1134/S0006350915020219}, doi = {10.1134/S0006350915020219}, abstract = {Quantitative evaluation of the accuracy of the rapid equilibrium assumption in steady-state enzyme kinetics was obtained for an arbitrary mechanism of an enzymatic reaction. This evaluation depends only on the structure and properties of an equilibrium segment; it is independent on the structure and properties of the remaining part (stationary) of the kinetic scheme. In the rapid equilibrium assumption, the smaller the values are of the edges that leave the equilibrium segment in relation to the values of the edges within the equilibrium segment, the higher the accuracy of determination of the reaction velocity is, as well as the concentrations of intermediates.}, language = {en}, number = {2}, urldate = {2016-09-27}, journal = {Biophysics}, author = {Vrzheshch, P. V.}, month = jun, year = {2015}, pages = {205--211}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JI3GH3B6\\S0006350915020219.html:text/html;Vrzheshch (2015) - The accuracy of rapid equilibrium assumption in steady-state enzyme kinetics is.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DM43R4V9\\Vrzheshch (2015) - The accuracy of rapid equilibrium assumption in steady-state enzyme kinetics is.pdf:application/pdf} } @article{gadsby_steady-state_1989, title = {Steady-state current-voltage relationship of the {Na}/{K} pump in guinea pig ventricular myocytes.}, volume = {94}, copyright = {© 1989 Rockefeller University Press}, issn = {0022-1295, 1540-7748}, url = {http://jgp.rupress.org.ezp.lib.unimelb.edu.au/content/94/3/511}, doi = {10.1085/jgp.94.3.511}, abstract = {Whole-cell currents were recorded in guinea pig ventricular myocytes at approximately 36 degrees C before, during, and after exposure to maximally effective concentrations of strophanthidin, a cardiotonic steroid and specific inhibitor of the Na/K pump. Wide-tipped pipettes, in combination with a device for exchanging the solution inside the pipette, afforded reasonable control of the ionic composition of the intracellular solution and of the membrane potential. Internal and external solutions were designed to minimize channel currents and Na/Ca exchange current while sustaining vigorous forward Na/K transport, monitored as strophanthidin-sensitive current. 100-ms voltage pulses from the -40 mV holding potential were used to determine steady-state levels of membrane current between -140 and +60 mV. Control experiments demonstrated that if the Na/K pump cycle were first arrested, e.g., by withdrawal of external K, or of both internal and external Na, then neither strophanthidin nor its vehicle, dimethylsulfoxide, had any discernible effect on steady-state membrane current. Further controls showed that, with the Na/K pump inhibited by strophanthidin, membrane current was insensitive to changes of external [K] between 5.4 and 0 mM and was little altered by changing the pipette [Na] from 0 to 50 mM. Strophanthidin-sensitive current therefore closely approximated Na/K pump current, and was virtually free of contamination by current components altered by the changes in extracellular [K] and intracellular [Na] expected to accompany pump inhibition. The steady-state Na/K pump current-voltage (I-V) relationship, with the pump strongly activated by 5.4 mM external K and 50 mM internal Na (and 10 mM ATP), was sigmoid in shape with a steep positive slope between about 0 and -100 mV, a less steep slope at more negative potentials, and an extremely shallow slope at positive potentials; no region of negative slope was found. That shape of I-V relationship can be generated by a two-state cycle with one pair of voltage-sensitive rate constants and one pair of voltage-insensitive rate constants: such a two-state scheme is a valid steady-state representation of a multi-state cycle that includes only a single voltage-sensitive step.}, language = {en}, number = {3}, urldate = {2016-10-05}, journal = {The Journal of General Physiology}, author = {Gadsby, D. C. and Nakao, M.}, month = sep, year = {1989}, pmid = {2607333}, pages = {511--537}, file = {Gadsby_Nakao (1989) - Steady-state current-voltage relationship of the Na-K pump in guinea pig.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7D2MZC4M\\Gadsby_Nakao (1989) - Steady-state current-voltage relationship of the Na-K pump in guinea pig.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ICCHXEKE\\511.html:text/html} } @article{despa_intracellular_2002, title = {Intracellular {Na}+ {Concentration} {Is} {Elevated} in {Heart} {Failure} {But} {Na}/{K} {Pump} {Function} {Is} {Unchanged}}, volume = {105}, copyright = {© 2002}, issn = {0009-7322, 1524-4539}, url = {http://circ.ahajournals.org.ezp.lib.unimelb.edu.au/content/105/21/2543}, doi = {10.1161/01.CIR.0000016701.85760.97}, abstract = {Background— Intracellular sodium concentration ([Na+]i) modulates cardiac contractile and electrical activity through Na/Ca exchange (NCX). Upregulation of NCX in heart failure (HF) may magnify the functional impact of altered [Na+]i. Methods and Results— We measured [Na+]i by using sodium binding benzofuran isophthalate in control and HF rabbit ventricular myocytes (HF induced by aortic insufficiency and constriction). Resting [Na+]i was 9.7±0.7 versus 6.6±0.5 mmol/L in HF versus control. In both cases, [Na+]i increased by ≈2 mmol/L when myocytes were stimulated (0.5 to 3 Hz). To identify the mechanisms responsible for [Na+]i elevation in HF, we measured the [Na+]i dependence of Na/K pump–mediated Na+ extrusion. There was no difference in Vmax (8.3±0.7 versus 8.0±0.8 mmol/L/min) or Km (9.2±1.0 versus 9.9±0.8 mmol/L in HF and control, respectively). Therefore, at measured [Na+]i levels, the Na/K pump rate is actually higher in HF. However, resting Na+ influx was twice as high in HF versus control (2.3±0.3 versus 1.1±0.2 mmol/L/min), primarily the result of a tetrodotoxin-sensitive pathway. Conclusions— Myocyte [Na+]i is elevated in HF as a result of higher diastolic Na+ influx (with unaltered Na/K-ATPase characteristics). In HF, the combined increased [Na+]i, decreased Ca2+ transient, and prolonged action potential all profoundly affect cellular Ca2+ regulation, promoting greater Ca2+ influx through NCX during action potentials. Notably, the elevated [Na+]i may be critical in limiting the contractile dysfunction observed in HF.}, language = {en}, number = {21}, urldate = {2016-10-06}, journal = {Circulation}, author = {Despa, Sanda and Islam, Mohammed A. and Weber, Christopher R. and Pogwizd, Steven M. and Bers, Donald M.}, month = may, year = {2002}, pmid = {12034663}, keywords = {calcium, heart failure, sodium}, pages = {2543--2548}, file = {Despa et al (2002) - Intracellular Na+ Concentration Is Elevated in Heart Failure But Na-K Pump.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\A67MZRUA\\Despa et al (2002) - Intracellular Na+ Concentration Is Elevated in Heart Failure But Na-K Pump.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\28UFRDGD\\2543.html:text/html} } @article{glitsch_electrophysiology_2001, title = {Electrophysiology of the {Sodium}-{Potassium}-{ATPase} in {Cardiac} {Cells}}, volume = {81}, copyright = {Copyright © 2001 The American Physiological Society}, issn = {0031-9333, 1522-1210}, url = {http://physrev.physiology.org.ezp.lib.unimelb.edu.au/content/81/4/1791}, abstract = {Like several other ion transporters, the Na+-K+ pump of animal cells is electrogenic. The pump generates the pump current I p. Under physiological conditions, I p is an outward current. It can be measured by electrophysiological methods. These methods permit the study of characteristics of the Na+-K+ pump in its physiological environment, i.e., in the cell membrane. The cell membrane, across which a potential gradient exists, separates the cytosol and extracellular medium, which have distinctly different ionic compositions. The introduction of the patch-clamp techniques and the enzymatic isolation of cells have facilitated the investigation of I p in single cardiac myocytes. This review summarizes and discusses the results obtained from I p measurements in isolated cardiac cells. These results offer new exciting insights into the voltage and ionic dependence of the Na+-K+ pump activity, its effect on membrane potential, and its modulation by hormones, transmitters, and drugs. They are fundamental for our current understanding of Na+-K+ pumping in electrically excitable cells.}, language = {en}, number = {4}, urldate = {2016-10-06}, journal = {Physiological Reviews}, author = {Glitsch, Helfried Günther}, month = jan, year = {2001}, pmid = {11581502}, pages = {1791--1826}, file = {Glitsch (2001) - Electrophysiology of the Sodium-Potassium-ATPase in Cardiac Cells.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BG4T2M72\\Glitsch (2001) - Electrophysiology of the Sodium-Potassium-ATPase in Cardiac Cells.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZDTIKA98\\1791.html:text/html} } @article{ould-moulaye_consistent_2002, title = {A consistent set of formation properties of nucleic acid compounds: {Nucleosides}, nucleotides and nucleotide-phosphates in aqueous solution}, volume = {387}, issn = {0040-6031}, shorttitle = {A consistent set of formation properties of nucleic acid compounds}, url = {http://www.sciencedirect.com/science/article/pii/S0040603101008140}, doi = {10.1016/S0040-6031(01)00814-0}, abstract = {Starting from formation properties of purines and pyrimidines, enthalpy of formation, Gibbs energy of formation, entropy of formation and heat capacity of several nucleosides, nucleotides and nucleotide-phosphates were calculated in dilute aqueous solution. For these calculations, the formation properties of ribose-1-phosphate were required and were calculated from data of various sources. Data for some enzymatic equilibrium constants were also used. To complete the set of formation properties of nucleosides and nucleotides, the energy contributions of some chemical bonds were calculated. The proposed values were reconciled with chemical and physical equilibrium data, validating the method of calculation used.}, number = {1}, urldate = {2016-10-07}, journal = {Thermochimica Acta}, author = {Ould-Moulaye, C. B and Dussap, C. G and Gros, J. B}, month = may, year = {2002}, keywords = {Enzymatic equilibrium, Formation properties, Nucleosides, Nucleotide-phosphates, Nucleotides, Sugar-phosphate}, pages = {1--15}, file = {Ould-Moulaye et al (2002) - A consistent set of formation properties of nucleic acid compounds.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WXNGDEVF\\Ould-Moulaye et al (2002) - A consistent set of formation properties of nucleic acid compounds.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7FJDTUIQ\\S0040603101008140.html:text/html} } @article{larowe_biomolecules_2006, title = {Biomolecules in hydrothermal systems: {Calculation} of the standard molal thermodynamic properties of nucleic-acid bases, nucleosides, and nucleotides at elevated temperatures and pressures}, volume = {70}, issn = {0016-7037}, shorttitle = {Biomolecules in hydrothermal systems}, url = {http://www.sciencedirect.com/science/article/pii/S0016703706001827}, doi = {10.1016/j.gca.2006.04.010}, abstract = {Calculation of the thermodynamic properties of biomolecules at high temperatures and pressures is fundamental to understanding the biogeochemistry of hydrothermal systems. Ample evidence indicates that hyperthermophilic microbes interact chemically with their mineralogical environment in these systems. Nevertheless, little is known about the thermodynamic properties of the biomolecules involved in such processes. Recent advances in theoretical biogeochemistry make it possible to calculate these properties using the limited experimental data available in the literature, together with correlation and group additivity algorithms, reference model compounds, and the revised HKF equations of state. This approach permits calculation of the standard molal thermodynamic properties of the 120 common protonated and deprotonated nucleotides and their constituent nucleic-acid bases and nucleosides as a function of temperature and pressure. The requisite equations of state parameters can be calculated from experimental standard molal heat capacities, volumes, and compressibilities reported in the literature for nucleic-acid bases and nucleosides. Because no calorimetric or densimetric data are available for the nucleotides, experimental heats of reaction taken from the literature were used together with correlation and group additivity algorithms to generate provisional values of the corresponding equations of state parameters for the nucleotides. The thermodynamic properties and revised HKF equations of state parameters generated in the present study can be used to carry out comprehensive mass transfer and Gibbs energy calculations to describe and quantify the chemical interaction of minerals and microbes in hydrothermal systems.}, number = {18}, urldate = {2016-10-07}, journal = {Geochimica et Cosmochimica Acta}, author = {LaRowe, Douglas E. and Helgeson, Harold C.}, month = sep, year = {2006}, pages = {4680--4724}, file = {LaRowe_Helgeson (2006) - Biomolecules in hydrothermal systems.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7BM49ZJJ\\LaRowe_Helgeson (2006) - Biomolecules in hydrothermal systems.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KZQXP5JK\\S0016703706001827.html:text/html} } @article{ould-moulaye_consistent_2001, title = {A consistent set of formation properties of nucleic acid compounds: {Purines} and pyrimidines in the solid state and in aqueous solution}, volume = {375}, issn = {0040-6031}, shorttitle = {A consistent set of formation properties of nucleic acid compounds}, url = {http://www.sciencedirect.com/science/article/pii/S0040603101005226}, doi = {10.1016/S0040-6031(01)00522-6}, abstract = {Enthalpy, Gibbs energy of formation, absolute entropy and heat capacity of purines and pyrimidines were calculated in the solid state and in dilute aqueous solution from a single reference state. Properties in the solid state were calculated from combustion data. Properties in dilute aqueous solution were calculated from solubility data and pK values after reconciliation. From this complete set of consistent data, the transformed properties were calculated. Missing data were made up using chemical group contribution techniques giving the formation properties of some chemical bonds specific to purines and pyrimidines.}, number = {1–2}, urldate = {2016-10-09}, journal = {Thermochimica Acta}, author = {Ould-Moulaye, C. B. and Dussap, C. G. and Gros, J. B.}, month = jul, year = {2001}, keywords = {Bioenergetics, Dissociation constants, Formation properties, Purine and pyrimidine bases, Thermodynamics}, pages = {93--107}, file = {Ould-Moulaye et al (2001) - A consistent set of formation properties of nucleic acid compounds.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2QAMI9AT\\Ould-Moulaye et al (2001) - A consistent set of formation properties of nucleic acid compounds.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8GMHXSNP\\S0040603101005226.html:text/html} } @article{chen_inputoutput_2009, title = {Input–output behavior of {ErbB} signaling pathways as revealed by a mass action model trained against dynamic data}, volume = {5}, copyright = {Copyright © 2009 EMBO and Nature Publishing Group. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.}, issn = {1744-4292, 1744-4292}, url = {http://msb.embopress.org/content/5/1/239}, doi = {10.1038/msb.2008.74}, abstract = {The ErbB signaling pathways, which regulate diverse physiological responses such as cell survival, proliferation and motility, have been subjected to extensive molecular analysis. Nonetheless, it remains poorly understood how different ligands induce different responses and how this is affected by oncogenic mutations. To quantify signal flow through ErbB‐activated pathways we have constructed, trained and analyzed a mass action model of immediate‐early signaling involving ErbB1–4 receptors (EGFR, HER2/Neu2, ErbB3 and ErbB4), and the MAPK and PI3K/Akt cascades. We find that parameter sensitivity is strongly dependent on the feature (e.g. ERK or Akt activation) or condition (e.g. EGF or heregulin stimulation) under examination and that this context dependence is informative with respect to mechanisms of signal propagation. Modeling predicts log‐linear amplification so that significant ERK and Akt activation is observed at ligand concentrations far below the Kd for receptor binding. However, MAPK and Akt modules isolated from the ErbB model continue to exhibit switch‐like responses. Thus, key system‐wide features of ErbB signaling arise from nonlinear interaction among signaling elements, the properties of which appear quite different in context and in isolation. Visual Overview SynopsisThe four transmembrane receptors of the ErbB family, of which the epidermal growth factor tyrosine kinase (EGFR or ErbB1) is the founding member, are widely expressed in human tissues and stimulate diverse cellular responses, such as proliferation, survival and motility. ErbB receptors have been studied extensively at a molecular level and several have been shown to play a central role in human cancer. ErbB2 (Her2), for example, is overexpressed in a subset of breast cancers and is the target of trastuzumab, an important anticancer drug. Signaling through ErbB receptors, and the downstream proteins they activate, is complex because ErbB1–4 combine to form both homo‐ and heterodimers having distinct affinities for 13 known ligands and intracellular adaptor proteins. Understanding and predicting how signaling varies with receptor mutation or overexpression is essentially impossible using informal reasoning and pictorial representations of signaling pathways.To address this challenge, we have constructed, trained and analyzed a mass action model of immediate‐early signaling involving four ErbB receptors, as well as the downstream MAP kinase and PI3K–Akt signaling pathways involved in regulating cell proliferation (Figure 1). Our model aims to capture as much mechanistic information as possible, based on an extensive literature, while accurately representing the responses of cells to two major ligand subclasses (EGF and heregulin in multiple tumor cell types). In assembling such a model, we encounter a number of challenges, among which the processes of entraining models to experimental data are the most serious. Mass action models are governed by two kinds of parameters: the concentrations of individual protein species, and the rate constants governing protein–protein association and enzyme catalysis. Models of cell signaling that are realistic at a molecular level may inevitably contain many parameters that are unknown a priori. These parameters can be estimated either by direct measurement (usually in vitro, raising the question how values obtained in dilute solution should be translated to a crowded intracellular environment) or through an inverse process in which the model is fitted to data. The processes of training a kinetic model on experimental data constrain only a subset of parameters. It is assumed by some that the presence of parametric uncertainty in trained models makes them useless; in fact the aim of fitting is to determine only the subset of parameters that determine model performance with sufficient accuracy from which meaningful hypotheses can be drawn. Methods to accomplish this with cell signaling models are in their infancy, and most biochemical models are parameterized based on generic or theoretical assumptions; systematic or rigorous analysis of parameters variation and uncertainty has been restricted to small idealized models. In the current study, we use iterative fitting to generate families of model fits with similar biochemical connectivity, but different values for unconstrained parameters. We then attempt to draw well‐substantiated inferences from the families of models.To ascertain which features of our ErbB model are conserved when parameterized by different sets of rate constants and concentrations, we calculated dynamic sensitivities of multiple observables; this serves to measure the ‘importance’ of each rate or species in affecting measurable outputs. Sensitivity analysis showed that despite degeneracy in parameter values among families of fits, many important features are conserved. However, the rank order of sensitive parameters is strongly influenced by the feature being examined. For example, the proteins and rate constants that influence ERK activation differed from those that influence Akt, and factors important at high ligand concentrations differ from those important at low concentrations. A picture of ErbB signaling emerges in which different physiological outputs can be mapped back to specific biochemical characteristics of signaling proteins under varying input conditions.One striking aspect of this input–output behavior involves the relationship between ligand concentration (the input) and the activities of ERK or Akt (the output). A priori, we might assume little activation of the ErbB pathway when the concentration of ligand is below receptor Kd. However, experiments demonstrate significant Akt and ERK activation (∼20\% maximal) and 100‐fold lower ligand. Moreover, as ligand levels rise we would expect the response to rise ∼9‐fold for every 81‐fold increase in ligand concentrations (representing standard binding thermodynamics). In contrast, we observe a log‐linear amplification relationship between ligand and output over a nearly 106 concentration range (Figure 7). To understand how this might arise, we have examined the performance of our parameterized ErbB model of and subsets of model comprising coupled reactions such as the MAP kinase cascade. We conclude that the unexpected log‐linear input–output behavior of the ErbB model arises from interactions between enzyme cascades that in isolation exhibit canonical Hill‐like behavior. Thus, we must now think carefully about the ways in which signaling modules interact so as to generate behavior that is quite different from what we would expect of the isolated molecules or small cascades.In conclusion, we describe an approach in constructing and analyzing models of cell signaling pathways that can incorporate substantial molecular detail, while remaining sensitive to the inability of experiments to fully constrain parametric complexity. By focusing on well‐substantiated model features, we attempt to understand the origins of an unexpected and physiologically significant characteristic of the ErbB network with regard to dose–response behavior. Looking forward we anticipate building on the current model by including more accurate representations of more reactions, while developing a rigorous approach to generating model‐derived hypotheses, the degree of belief of which is determined by the underlying uncertainty in the model and the data. We will then be in a position to reliably understand cellular physiology in terms of molecular mechanism. A complex mass‐action model of immediate‐early ErbB signaling in human cells yields new biochemical insight despite its non‐identifiability and resulting parametric uncertaintySensitivity analysis reveals a strong relationship between those parameters that are important for model dynamics and the specific physiological feature being analyzed: biochemical values that are highly significant for some responses are unimportant for othersProteins downstream in the ErbB signaling cascade are activated to substantial levels at ligand concentrations several orders of magnitude below those that result in appreciable receptor‐ligand binding or receptor phosphorylationThe extreme sensitivity of ErbB receptors to low ligand concentrations arises from the ability of MAPK and PI3K‐Akt kinase cascades to amplify signals in a highly non‐linear manner; this behavior is lost when the cascades are isolated from the larger ErbB network, demonstrating context sensitivity in their operation}, language = {en}, number = {1}, urldate = {2016-10-11}, journal = {Molecular Systems Biology}, author = {Chen, William W. and Schoeberl, Birgit and Jasper, Paul J. and Niepel, Mario and Nielsen, Ulrik B. and Lauffenburger, Douglas A. and Sorger, Peter K.}, month = jan, year = {2009}, pmid = {19156131}, keywords = {EGFR, ErbB, ODE model, parameter optimization, signal transduction}, pages = {239}, file = {Chen et al (2009) - Input–output behavior of ErbB signaling pathways as revealed by a mass action.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QQPSWKXK\\Chen et al (2009) - Input–output behavior of ErbB signaling pathways as revealed by a mass action.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CS8SWVQ4\\239.html:text/html} } @article{liepe_framework_2014, title = {A framework for parameter estimation and model selection from experimental data in systems biology using approximate {Bayesian} computation}, volume = {9}, copyright = {© 2014 Nature Publishing Group, a division of Macmillan Publishers Limited. All Rights Reserved.}, issn = {1754-2189}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nprot/journal/v9/n2/abs/nprot.2014.025.html}, doi = {10.1038/nprot.2014.025}, abstract = {As modeling becomes a more widespread practice in the life sciences and biomedical sciences, researchers need reliable tools to calibrate models against ever more complex and detailed data. Here we present an approximate Bayesian computation (ABC) framework and software environment, ABC-SysBio, which is a Python package that runs on Linux and Mac OS X systems and that enables parameter estimation and model selection in the Bayesian formalism by using sequential Monte Carlo (SMC) approaches. We outline the underlying rationale, discuss the computational and practical issues and provide detailed guidance as to how the important tasks of parameter inference and model selection can be performed in practice. Unlike other available packages, ABC-SysBio is highly suited for investigating, in particular, the challenging problem of fitting stochastic models to data. In order to demonstrate the use of ABC-SysBio, in this protocol we postulate the existence of an imaginary reaction network composed of seven interrelated biological reactions (involving a specific mRNA, the protein it encodes and a post-translationally modified version of the protein), a network that is defined by two files containing 'observed' data that we provide as supplementary information. In the first part of the PROCEDURE, ABC-SysBio is used to infer the parameters of this system, whereas in the second part we use ABC-SysBio's relevant functionality to discriminate between two different reaction network models, one of them being the 'true' one. Although computationally expensive, the additional insights gained in the Bayesian formalism more than make up for this cost, especially in complex problems. View full text}, language = {en}, number = {2}, urldate = {2016-10-11}, journal = {Nature Protocols}, author = {Liepe, Juliane and Kirk, Paul and Filippi, Sarah and Toni, Tina and Barnes, Chris P. and Stumpf, Michael P. H.}, month = feb, year = {2014}, keywords = {Bayesian inference, bioinformatics, Computational models, Software}, pages = {439--456}, file = {Liepe et al (2014) - A framework for parameter estimation and model selection from experimental data.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PFDEBT6Q\\Liepe et al (2014) - A framework for parameter estimation and model selection from experimental data.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\98BDM6DN\\nprot.2014.025.html:text/html} } @article{oates_causal_2014, title = {Causal network inference using biochemical kinetics}, volume = {30}, issn = {1367-4803, 1460-2059}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/30/17/i468}, doi = {10.1093/bioinformatics/btu452}, abstract = {Motivation: Networks are widely used as structural summaries of biochemical systems. Statistical estimation of networks is usually based on linear or discrete models. However, the dynamics of biochemical systems are generally non-linear, suggesting that suitable non-linear formulations may offer gains with respect to causal network inference and aid in associated prediction problems. Results: We present a general framework for network inference and dynamical prediction using time course data that is rooted in non-linear biochemical kinetics. This is achieved by considering a dynamical system based on a chemical reaction graph with associated kinetic parameters. Both the graph and kinetic parameters are treated as unknown; inference is carried out within a Bayesian framework. This allows prediction of dynamical behavior even when the underlying reaction graph itself is unknown or uncertain. Results, based on (i) data simulated from a mechanistic model of mitogen-activated protein kinase signaling and (ii) phosphoproteomic data from cancer cell lines, demonstrate that non-linear formulations can yield gains in causal network inference and permit dynamical prediction and uncertainty quantification in the challenging setting where the reaction graph is unknown. Availability and implementation: MATLAB R2014a software is available to download from warwick.ac.uk/chrisoates. Contact: c.oates@warwick.ac.uk or sach@mrc-bsu.cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online.}, language = {en}, number = {17}, urldate = {2016-10-11}, journal = {Bioinformatics}, author = {Oates, Chris J. and Dondelinger, Frank and Bayani, Nora and Korkola, James and Gray, Joe W. and Mukherjee, Sach}, month = sep, year = {2014}, pmid = {25161235}, pages = {i468--i474}, file = {Oates et al (2014) - Causal network inference using biochemical kinetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CVG6JK75\\Oates et al (2014) - Causal network inference using biochemical kinetics.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PB8JXHHP\\i468.html:text/html} } @article{srividhya_reconstructing_2007, title = {Reconstructing biochemical pathways from time course data}, volume = {7}, issn = {1615-9861}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1002/pmic.200600428/abstract}, doi = {10.1002/pmic.200600428}, abstract = {Time series data on biochemical reactions reveal transient behavior, away from chemical equilibrium, and contain information on the dynamic interactions among reacting components. However, this information can be difficult to extract using conventional analysis techniques. We present a new method to infer biochemical pathway mechanisms from time course data using a global nonlinear modeling technique to identify the elementary reaction steps which constitute the pathway. The method involves the generation of a complete dictionary of polynomial basis functions based on the law of mass action. Using these basis functions, there are two approaches to model construction, namely the general to specific and the specific to general approach. We demonstrate that our new methodology reconstructs the chemical reaction steps and connectivity of the glycolytic pathway of Lactococcus lactis from time course experimental data.}, language = {en}, number = {6}, urldate = {2016-10-11}, journal = {PROTEOMICS}, author = {Srividhya, Jeyaraman and Crampin, Edmund J. and McSharry, Patrick E. and Schnell, Santiago}, month = mar, year = {2007}, keywords = {Biochemical network inference, Model selection, Reverse engineering, Systems Biology, Time series data}, pages = {828--838}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8G6GJR7E\\abstract.html:text/html;Srividhya et al (2007) - Reconstructing biochemical pathways from time course data.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I4D98PM7\\Srividhya et al (2007) - Reconstructing biochemical pathways from time course data.pdf:application/pdf} } @article{semenov_autocatalytic_2016, title = {Autocatalytic, bistable, oscillatory networks of biologically relevant organic reactions}, volume = {537}, copyright = {© 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.}, issn = {0028-0836}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nature/journal/v537/n7622/abs/nature19776.html}, doi = {10.1038/nature19776}, abstract = {Networks of organic chemical reactions are important in life and probably played a central part in its origin. Network dynamics regulate cell division, circadian rhythms, nerve impulses and chemotaxis, and guide the development of organisms. Although out-of-equilibrium networks of chemical reactions have the potential to display emergent network dynamics such as spontaneous pattern formation, bistability and periodic oscillations, the principles that enable networks of organic reactions to develop complex behaviours are incompletely understood. Here we describe a network of biologically relevant organic reactions (amide formation, thiolate–thioester exchange, thiolate–disulfide interchange and conjugate addition) that displays bistability and oscillations in the concentrations of organic thiols and amides. Oscillations arise from the interaction between three subcomponents of the network: an autocatalytic cycle that generates thiols and amides from thioesters and dialkyl disulfides; a trigger that controls autocatalytic growth; and inhibitory processes that remove activating thiol species that are produced during the autocatalytic cycle. In contrast to previous studies that have demonstrated oscillations and bistability using highly evolved biomolecules (enzymes and DNA) or inorganic molecules of questionable biochemical relevance (for example, those used in Belousov–Zhabotinskii-type reactions), the organic molecules we use are relevant to metabolism and similar to those that might have existed on the early Earth. By using small organic molecules to build a network of organic reactions with autocatalytic, bistable and oscillatory behaviour, we identify principles that explain the ways in which dynamic networks relevant to life could have developed. Modifications of this network will clarify the influence of molecular structure on the dynamics of reaction networks, and may enable the design of biomimetic networks and of synthetic self-regulating and evolving chemical systems.}, language = {en}, number = {7622}, urldate = {2016-10-12}, journal = {Nature}, author = {Semenov, Sergey N. and Kraft, Lewis J. and Ainla, Alar and Zhao, Mengxia and Baghbanzadeh, Mostafa and Campbell, Victoria E. and Kang, Kyungtae and Fox, Jerome M. and Whitesides, George M.}, month = sep, year = {2016}, keywords = {Chemical origin of life, Nonlinear phenomena, Reaction kinetics and dynamics}, pages = {656--660}, file = {Semenov et al (2016) - Autocatalytic, bistable, oscillatory networks of biologically relevant organic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IHNC3CZG\\Semenov et al (2016) - Autocatalytic, bistable, oscillatory networks of biologically relevant organic.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QWZ3MC8F\\nature19776.html:text/html} } @article{august_new_2009, title = {A {New} {Computational} {Tool} for {Establishing} {Model} {Parameter} {Identifiability}}, volume = {16}, issn = {1066-5277}, url = {http://online.liebertpub.com.ezp.lib.unimelb.edu.au/doi/abs/10.1089/cmb.2008.0211}, doi = {10.1089/cmb.2008.0211}, abstract = {We describe a novel method to establish a priori whether the parameters of a nonlinear dynamical system are identifiable—that is, whether they can be deduced from output data (experimental observations). This is an important question as usually identifiability is assumed, and parameters are sought without first establishing whether these can be inferred from a set of measurements. We highlight the connections between parameter identifiability and state observability. We show how observability criteria can be used to check for identifiability, and we use new, state of the art computational tools to implement our approach. Nonlinear dynamical systems are prevalent in systems biology, where they are often used to represent a biological system. Thus, examples from biology are used to illustrate our method.}, number = {6}, urldate = {2016-10-13}, journal = {Journal of Computational Biology}, author = {August, Elias and Papachristodoulou, Antonis}, month = jun, year = {2009}, pages = {875--885}, file = {August_Papachristodoulou (2009) - A New Computational Tool for Establishing Model Parameter Identifiability.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XUHZQ5IF\\August_Papachristodoulou (2009) - A New Computational Tool for Establishing Model Parameter Identifiability.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4UDVDHSG\\cmb.2008.html:text/html} } @article{guynn_equilibrium_1973, title = {The {Equilibrium} {Constants} of the {Adenosine} {Triphosphate} {Hydrolysis} and the {Adenosine} {Triphosphate}-{Citrate} {Lyase} {Reactions}}, volume = {248}, issn = {0021-9258, 1083-351X}, url = {http://www.jbc.org/content/248/20/6966}, abstract = {The observed standard free energy change (ΔG0obs) for the hydrolysis of the terminal pyrophosphate bond of ATP has been experimentally determined under physiological conditions using an entirely new set of reactions. The observed equilibrium constant (Kobs) for the combined reactions of acetate kinase (EC 2.7.2.1) and phosphate acetyltransferase (EC 2.3.1.8) has been determined at 38°, pH 7.0, ionic strength 0.25, and varying free [Mg2+]. The Kobs of these combined reactions reflects the difference between ΔG0obs for the hydrolysis of acetyl-CoA and the ΔG0obs for the hydrolysis of ATP. Using Σ and square brackets to indicate total concentration, Kobs = [ΣADP][ΣPi]/[ΣATP] x [Acetyl-CoA]/[ΣAcetate][CoA] The observed value of this combined equilibrium constant varies with free [Mg2+], being 0.984 ± 0.009 when [Mg2+] = 0 and 0.218 ± 0.002 when free [Mg2+] = 10-3 m. The ΔG0obs for the hydrolysis of acetyl-CoA is virtually unaffected by the free [Mg2+] and has been previously determined to be -8.54 Cal per mole (-35.75 kJ per mole) under the same conditions of temperature, pH, and ionic strength. Therefore at pH 7.0, at ionic strength 0.25, at 38°, and taking the standard state of liquid water to have activity = unity ([H2O] = 1) the ΔG0obs for the reaction [see PDF for equation] can be calculated to be -8.53 Cal per mole (-35.69 kJ per mole) at [Mg2+] = 0 and -7.60 Cal per mole (-31.80 kJ per mole) at [Mg2+] = 10-3 m. The corresponding values of Kobs for the ATP hydrolysis reaction are 9.86 x 105 m ([Mg2+] = 0) and 2.19 x 105 m ([Mg2+] = 10-3 m). Equations have been developed for calculating from the experimental data the ΔG0obs of ATP hydrolysis at different free magnesium and hydrogen ion concentrations. The Kobs of ATP hydrolysis has been used in combination with the Kobs of the citrate synthase reaction (EC 4.1.3.7) to calculate the Kobs of the ATP-citrate lyase reaction (EC 4.1.3.8) Kobs = [ΣADP][Acetyl-CoA] [ΣPi] [ΣOxaloacetate]/[ΣATP] [CoA] [ΣCitrate] Under the same near physiological conditions of 38°, pH 7.0, and ionic strength 0.25, the value of Kobs for the ATP-citrate lyase reaction was found to be very sensitive to the free [Mg2+], being 0.975 m at [Mg2+] = 0 and 0.0985 m when free [Mg2+] = 10-3 m.}, language = {en}, number = {20}, urldate = {2016-10-17}, journal = {Journal of Biological Chemistry}, author = {Guynn, Robert W. and Veech, Richard L.}, month = oct, year = {1973}, pmid = {4355193}, pages = {6966--6972}, file = {Guynn_Veech (1973) - The Equilibrium Constants of the Adenosine Triphosphate Hydrolysis and the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SENC7T9C\\Guynn_Veech (1973) - The Equilibrium Constants of the Adenosine Triphosphate Hydrolysis and the.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4MRZ87TU\\6966.html:text/html} } @article{goldberg_standards_2014, series = {Reporting {Enzymology} {Data} – {STRENDA} {Recommendations} and {Beyond}}, title = {Standards in biothermodynamics}, volume = {1}, issn = {2213-0209}, url = {http://www.sciencedirect.com/science/article/pii/S2213020914000020}, doi = {10.1016/j.pisc.2014.02.001}, abstract = {The field of biothermodynamics encompasses physical property measurements on biochemical and biological systems. This chapter reviews the status of standards documents that are pertinent to biothermodynamics as well as recommendations that have been made for the reporting of experimental results. The importance of standards in nomenclature, symbols, units, and uncertainties is discussed and a summary of sources of data for biochemical substances and reactions is given.}, number = {1–6}, urldate = {2016-10-18}, journal = {Perspectives in Science}, author = {Goldberg, Robert N.}, month = may, year = {2014}, keywords = {Apparent equilibrium constant, Calorimetry, data, Thermodynamics}, pages = {7--14}, file = {Goldberg (2014) - Standards in biothermodynamics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CAXRM8GK\\Goldberg (2014) - Standards in biothermodynamics.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\PDSXSSDQ\\S2213020914000020.html:text/html} } @book{cox_codata_1989, title = {{CODATA} key values for thermodynamics}, publisher = {Chem/Mats-Sci/E}, author = {Cox, J. D. and Wagman, Donald D. and Medvedev, Vadim Andreevich}, year = {1989} } @article{linstrom_nist_2001, title = {{NIST} {Chemistry} webbook; {NIST} standard reference database {No}. 69}, url = {http://www.citeulike.org/group/14458/article/10885717}, urldate = {2016-10-18}, author = {Linstrom, Peter J. and Mallard, W. G.}, year = {2001}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2W6HH4JG\\10885717.html:text/html} } @article{hepler_standard_1996, title = {Standard state heat capacities of aqueous electrolytes and some related undissociated species}, volume = {74}, issn = {0008-4042}, url = {http://www.nrcresearchpress.com.ezp.lib.unimelb.edu.au/doi/abs/10.1139/v96-069}, doi = {10.1139/v96-069}, abstract = {Uses of heat capacities of solutions of electrolytes are reviewed, with a particular emphasis on the standard state partial molar heat capacities and their applications to calculations of the effects of temperature on equilibrium constants, electrode potentials, enthalpies, and entropies. Methods of obtaining these standard partial molar heat capacities are summarized, followed by comparisons of values obtained in different ways. Many of the "best" such heat capacities are collected and then used as the basis for establishing single-ion heat capacities based on the convention that CpO(H+) = 0, followed by illustrations of the convenient use of these quantities. Finally, there is brief discussion of theoretical analysis of these standard partial molar heat capacities in relation to ion–solvent interactions. Key words: heat capacities, electrolytes; aqueous solutions, heat capacities; thermodynamics, electrolytes., On présente une revue de l'utilisation des capacités calorifiques de solutions d'électrolytes en insistant d'une façon particulière sur les capacités calorifiques molaires partielles dans l'état standard et leurs applications aux calculs des effets de la température sur les constantes d'équilibre, les potentiels d'électrode, les enthalpies et les entropies. On résume les méthodes d'obtenir ces capacités calorifiques molaires partielles standard et on présente ensuite un comparaison des diverses valeurs obtenues d'après les diverses manières. Plusieurs des «meilleures» propriétés, comme les capacités calorifiques, ont été rassemblées et ont ensuite été utilisées comme base pour l'établissement des capacités calorifiques d'un seul ion en se basant sur la convention que CpO(H+) = 0; elles sont suivies par des illustrations sur l'utilisation commode de ces quantités. Enfin, on présente une brève discussion de l'analyse théorique de ces capacités calorifiques molaires partielles standard en relation avec les i...}, number = {5}, urldate = {2016-10-19}, journal = {Canadian Journal of Chemistry}, author = {Hepler, Loren G. and Hovey, Jamey K.}, month = may, year = {1996}, pages = {639--649}, file = {Hepler_Hovey (1996) - Standard state heat capacities of aqueous electrolytes and some related.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EX782NUM\\Hepler_Hovey (1996) - Standard state heat capacities of aqueous electrolytes and some related.pdf:application/pdf;NRC Research Press Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\997XD57N\\v96-069.html:text/html} } @article{henkel_notions_2016, title = {Notions of similarity for systems biology models}, issn = {1467-5463, 1477-4054}, url = {http://bib.oxfordjournals.org/content/early/2016/10/11/bib.bbw090}, doi = {10.1093/bib/bbw090}, abstract = {Systems biology models are rapidly increasing in complexity, size and numbers. When building large models, researchers rely on software tools for the retrieval, comparison, combination and merging of models, as well as for version control. These tools need to be able to quantify the differences and similarities between computational models. However, depending on the specific application, the notion of ‘similarity’ may greatly vary. A general notion of model similarity, applicable to various types of models, is still missing. Here we survey existing methods for the comparison of models, introduce quantitative measures for model similarity, and discuss potential applications of combined similarity measures. To frame model comparison as a general problem, we describe a theoretical approach to defining and computing similarities based on a combination of different model aspects. The six aspects that we define as potentially relevant for similarity are underlying encoding, references to biological entities, quantitative behaviour, qualitative behaviour, mathematical equations and parameters and network structure. We argue that future similarity measures will benefit from combining these model aspects in flexible, problem-specific ways to mimic users’ intuition about model similarity, and to support complex model searches in databases.}, language = {en}, urldate = {2016-10-23}, journal = {Briefings in Bioinformatics}, author = {Henkel, Ron and Hoehndorf, Robert and Kacprowski, Tim and Knüpfer, Christian and Liebermeister, Wolfram and Waltemath, Dagmar}, month = oct, year = {2016}, pmid = {27742665}, keywords = {information retrieval, model version control, network model, SBML, Systems Biology}, pages = {bbw090}, file = {Henkel et al (2016) - Notions of similarity for systems biology models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IJIKZ38D\\Henkel et al (2016) - Notions of similarity for systems biology models.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EFXV3AHT\\bib.bbw090.html:text/html} } @article{gadsby_ion_2009, title = {Ion channels versus ion pumps: the principal difference, in principle}, volume = {10}, copyright = {© 2009 Nature Publishing Group}, issn = {1471-0072}, shorttitle = {Ion channels versus ion pumps}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/nrm/journal/v10/n5/abs/nrm2668.html}, doi = {10.1038/nrm2668}, abstract = {The incessant traffic of ions across cell membranes is controlled by two kinds of border guards: ion channels and ion pumps. Open channels let selected ions diffuse rapidly down electrical and concentration gradients, whereas ion pumps labour tirelessly to maintain the gradients by consuming energy to slowly move ions thermodynamically uphill. Because of the diametrically opposed tasks and the divergent speeds of channels and pumps, they have traditionally been viewed as completely different entities, as alike as chalk and cheese. But new structural and mechanistic information about both of these classes of molecular machines challenges this comfortable separation and forces its re-evaluation.}, language = {en}, number = {5}, urldate = {2016-10-27}, journal = {Nature Reviews Molecular Cell Biology}, author = {Gadsby, David C.}, month = may, year = {2009}, pages = {344--352}, file = {Gadsby (2009) - Ion channels versus ion pumps.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GGRXED77\\Gadsby (2009) - Ion channels versus ion pumps.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\E2V4PVKM\\nrm2668.html:text/html} } @article{van_der_schaft_characterization_2010, title = {Characterization and partial synthesis of the behavior of resistive circuits at their terminals}, volume = {59}, issn = {0167-6911}, url = {http://www.sciencedirect.com/science/article/pii/S0167691110000563}, doi = {10.1016/j.sysconle.2010.05.005}, abstract = {The external behavior of linear resistive circuits with terminals is characterized as a linear input–output map given by a weighted Laplacian matrix. Conditions are derived for shaping the external behavior of the circuit by interconnection with an additional resistive circuit.}, number = {7}, urldate = {2016-10-27}, journal = {Systems \& Control Letters}, author = {van der Schaft, Arjan}, month = jul, year = {2010}, keywords = {Boundary vertices, Kirchhoff’s laws, Laplacian matrix, Open graphs, Partial synthesis by interconnection, Schur complements}, pages = {423--428}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\85NWUTRB\\S0167691110000563.html:text/html;van der Schaft (2010) - Characterization and partial synthesis of the behavior of resistive circuits at.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CU37W9ZB\\van der Schaft (2010) - Characterization and partial synthesis of the behavior of resistive circuits at.pdf:application/pdf} } @article{hackett_systems-level_2016, title = {Systems-level analysis of mechanisms regulating yeast metabolic flux}, volume = {354}, copyright = {Copyright © 2016, American Association for the Advancement of Science}, issn = {0036-8075, 1095-9203}, url = {http://science.sciencemag.org.ezp.lib.unimelb.edu.au/content/354/6311/aaf2786}, doi = {10.1126/science.aaf2786}, abstract = {Quantitation of metabolic pathway regulation Although metabolic biochemical pathways are well understood, less is known about precisely how reaction rates or fluxes through the various enzymes are controlled. Hackett et al. developed a method to quantitate such regulatory influence in yeast. They monitored concentrations of metabolites, enzymes, and potential regulators by LC-MS/MS (liquid chromatography–tandem mass spectrometry) and isotope ratio measurements for 56 reactions, over 100 metabolites, and 370 metabolic enzymes in yeast in 25 different steady-state conditions. Bayesian analysis was used to examine the probability of regulatory interactions. Regulation of flux through the pathways was predominantly controlled by changes in the concentration of small-molecule metabolites rather than changes in enzyme abundance. The analysis also revealed previously unrecognized regulation between pathways. Science, this issue p. 432 Structured Abstract INTRODUCTIONMetabolism is among the most strongly conserved processes across all domains of life and is crucial for both bioengineering and disease research, yet we still have an unclear understanding of how metabolic rates (fluxes) are determined. Qualitatively, this deficiency involves missing knowledge of enzyme regulators. Quantitatively, it involves limited understanding of the relative contributions of enzyme and metabolite concentrations in controlling flux across physiological conditions. Addressing these gaps has been challenging because in vitro biochemical approaches lack the physiological context, whereas models of cellular metabolic dynamics have limited capacity for identifying or quantitating specific regulatory events because of overall model complexity. RATIONALEFlux through individual metabolic reactions is directly determined by the concentrations of enzyme, substrates, products, and any allosteric regulators, as captured quantitatively by a Michaelis-Menten–style reaction equation. Analogous to how experimental variation of reaction species in vitro allows for the inference of regulators and reaction equation kinetic parameters, physiological changes in flux entail a change in reaction species that can be used to determine reaction equations on the basis of cellular data. This requires measurement across multiple biological conditions of flux, enzyme concentrations, and metabolite concentrations. We reasoned that chemostat cultures could be used to induce predictable and strong flux changes, with changes in enzymes and metabolites measurable by proteomics and metabolomics. By directly relating cellular flux to the reaction species that determine it, we can carry out regulatory inference at the level of single metabolic reactions by using cellular data. An important benefit is that the physiological significance of any identified regulator is implicit from its role in determining cellular flux. RESULTSHere we introduce systematic identification of meaningful metabolic enzyme regulation (SIMMER). We measured fluxes, and metabolite and enzyme concentrations, in each of 25 yeast chemostats. For each of 56 reactions for which the flux, enzyme, and substrates were measured, we determined whether variation in measured flux could be explained by simple Michaelis-Menten kinetics. We also evaluated alternative models of each reaction’s kinetics that included a suite of allosteric regulators drawn from across all organisms. For 46 reactions, we were able to identify a useful kinetic model, with 17 reactions not including any regulation and 29 reactions being regulated by one to two allosteric regulators. Three previously unrecognized cross-pathway regulatory interactions were validated biochemically. These included inhibition of pyruvate kinase by citrate and inhibition of pyruvate decarboxylase by phenypyruvate. These metabolites accumulated and thereby curtailed glycolytic outflow and ethanol production in nitrogen-limited yeast. For well-supported reaction forms, we were able to determine the extent to which nutrient-based changes in flux were determined by changes in the concentrations of individual reaction species. We find that substrates are the most important determinant of fluxes in general, with enzymes and allosteric regulators having a comparably important role in the case of physiologically irreversible reactions. CONCLUSIONBy connecting changes in flux to their root cause, SIMMER parallels classic in vitro approaches, but it allows simultaneous testing of numerous regulators of many reactions under physiological conditions. Its application to yeast showed that changes in flux across nutrient conditions are predominantly due to metabolite, not enzyme, levels. Thus, yeast metabolism is substantially self-regulating. {\textless}img class="fragment-image" src="https://d2ufo47lrtsv5s.cloudfront.net/content/sci/354/6311/aaf2786/F1.medium.gif"/{\textgreater} Download high-res image Open in new tab Download Powerpoint Integrative analysis of fluxes and metabolite and enzyme concentrations by SIMMER.Measured flux is related, on a reaction-by-reaction basis, to enzyme and metabolite concentrations through a Michaelis-Menten equation. The extent to which variation in flux across experimental conditions can be explained by the enzyme, substrates, and products is assessed. If unregulated kinetics disagrees with the measured flux, we test a set of possible allosteric regulators to determine which, if any, regulators are supported on the basis of improvement in fit. Cellular metabolic fluxes are determined by enzyme activities and metabolite abundances. Biochemical approaches reveal the impact of specific substrates or regulators on enzyme kinetics but do not capture the extent to which metabolite and enzyme concentrations vary across physiological states and, therefore, how cellular reactions are regulated. We measured enzyme and metabolite concentrations and metabolic fluxes across 25 steady-state yeast cultures. We then assessed the extent to which flux can be explained by a Michaelis-Menten relationship between enzyme, substrate, product, and potential regulator concentrations. This revealed three previously unrecognized instances of cross-pathway regulation, which we biochemically verified. One of these involved inhibition of pyruvate kinase by citrate, which accumulated and thereby curtailed glycolytic outflow in nitrogen-limited yeast. Overall, substrate concentrations were the strongest driver of the net rates of cellular metabolic reactions, with metabolite concentrations collectively having more than double the physiological impact of enzymes. Metabolomics, proteomics, and flux analysis are used to dissect quantitatively metabolic regulation in living yeast. Metabolomics, proteomics, and flux analysis are used to dissect quantitatively metabolic regulation in living yeast.}, language = {en}, number = {6311}, urldate = {2016-10-31}, journal = {Science}, author = {Hackett, Sean R. and Zanotelli, Vito R. T. and Xu, Wenxin and Goya, Jonathan and Park, Junyoung O. and Perlman, David H. and Gibney, Patrick A. and Botstein, David and Storey, John D. and Rabinowitz, Joshua D.}, month = oct, year = {2016}, pmid = {27789812}, pages = {aaf2786}, file = {Hackett et al (2016) - Systems-level analysis of mechanisms regulating yeast metabolic flux.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\M9X4C45Q\\Hackett et al (2016) - Systems-level analysis of mechanisms regulating yeast metabolic flux.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\78FD98I9\\aaf2786.html:text/html} } @article{catchpole_detecting_1997, title = {Detecting parameter redundancy}, volume = {84}, issn = {0006-3444, 1464-3510}, url = {http://biomet.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/84/1/187}, doi = {10.1093/biomet/84.1.187}, abstract = {Necessary and sufficient conditions are established for the parameter redundancy of a wide class of nonlinear models for data distributed according to the exponential family. The likelihood surfaces for parameter-redundant models possess completely flat ridges. Whether a model is parameter redundant can be established by checking the rank of a derivative matrix, using a symbolic algebra package. A feature of contingency table applications is the need to extend conclusions from particular to general dimensions. We meet this via an extension theorem. Examples are given from the area of animal survival estimation using mark-recapture/recovery data.}, language = {en}, number = {1}, urldate = {2016-11-02}, journal = {Biometrika}, author = {Catchpole, E. A. and Morgan, B. J. T.}, month = mar, year = {1997}, keywords = {Contingency table, Diagnostics, Identifiability, Likelihood, Nonlinear model, Parameter redundancy, Recapture data, Recovery data, Ridge, Symbolic algebra}, pages = {187--196}, file = {Catchpole_Morgan (1997) - Detecting parameter redundancy.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TZ9NUFXU\\Catchpole_Morgan (1997) - Detecting parameter redundancy.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JB4XNNC2\\187.html:text/html} } @article{bamber_how_2000, title = {How to {Assess} a {Model}'s {Testability} and {Identifiability}}, volume = {44}, issn = {0022-2496}, url = {http://www.sciencedirect.com/science/article/pii/S0022249699912750}, doi = {10.1006/jmps.1999.1275}, abstract = {Formal definitions are given of the following intuitive concepts: (a) A model is quantitatively testable if its predictions are highly precise and narrow. (b) A model is identifiable if the values of its parameters can be ascertained from empirical observations. (c) A model is redundant if the values of some parameters can be deduced from others or if the values of some observables can be deduced from others. Various rules of thumb for nonredundant models are examined. The Counting Rule states that a model is quantitatively testable if and only if it has fewer parameters than observables. This rule can be safely applied only to identifiable models. If a model is unidentifiable, one must apply a generalization of the Counting Rule known as the Jacobian Rule. This rule states that a model is quantitatively testable if and only if the maximum rank (i.e., the number of linearly independent columns) of its Jacobian matrix (i.e., the matrix of partial derivatives of the function that maps parameter values to the predicted values of observables) is smaller than the number of observables. The Identifiability Rule states that a model is identifiable if and only if the maximum rank of its Jacobian matrix equals the number of parameters. The conclusions provided by these rules are only presumptive. To reach definitive conclusions, additional analyses must be performed. To illustrate the foregoing, the quantitative testability and identifiability of linear models and of discrete-state models are analyzed.}, number = {1}, urldate = {2016-11-03}, journal = {Journal of Mathematical Psychology}, author = {Bamber, Donald and van Santen, Jan P. H}, month = mar, year = {2000}, pages = {20--40}, file = {Bamber_van Santen (2000) - How to Assess a Model's Testability and Identifiability.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3SIGES5S\\Bamber_van Santen (2000) - How to Assess a Model's Testability and Identifiability.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W7KSQ97U\\S0022249699912750.html:text/html} } @article{sakoda_determination_1976, title = {Determination of the {Best}-{Fit} {Values} of {Kinetic} {Parameters} of the {Michaelis}-{Menten} {Equation} by the {Method} of {Least} {Squares} with the {Taylor} {Expansion}}, volume = {80}, issn = {0021-924X,}, url = {http://jb.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/80/3/547}, abstract = {The best-fit values of the Michaelis constant (Km) and the maximum veloeity (V) in the Michaelis-Menten equation can be obtained by the method of least squares with the Taylor expansion for the sum of squares of the absolute residual, i.e., the difference between the observed velocity and the corresponding velocity by calculation. This method makes it possible to determine the values of Km and V not in a trial-and-error manner but in a deductive and unique manner after some iterative procedures starting from arbitrary approximate values of Km and V. These values can be said to be uniquely determined for a set of data as the finally converged values are no longer dependent upon the initial approximate values of Km and V. It is also very important to obtain initial approximate values of parameters for the application of the method described above. A simple method is proposed to estimate the approximate values of parameters involved in fractional functions. The method of rearrangement after canceling the denominator of a fractional functions. can be utilized to obtain approximate values, not only for cases of two unknown parameters such as the Michaelis-Menten equation, but also for cases with more than two unknowns.}, language = {en}, number = {3}, urldate = {2016-11-13}, journal = {Journal of Biochemistry}, author = {Sakoda, Mitsuaki and Hiromi, Keitaro}, month = sep, year = {1976}, pmid = {977553}, pages = {547--555}, file = {Sakoda_Hiromi (1976) - Determination of the Best-Fit Values of Kinetic Parameters of the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2RQNGAAE\\Sakoda_Hiromi (1976) - Determination of the Best-Fit Values of Kinetic Parameters of the.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GV3TKESU\\547.html:text/html} } @article{hadeler_least-squares_2007, title = {Least-squares problems for {Michaelis}–{Menten} kinetics}, volume = {30}, issn = {1099-1476}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1002/mma.835/abstract}, doi = {10.1002/mma.835}, abstract = {The Michaelis–Menten kinetics is fundamental in chemical and physiological reaction theory. The problem of parameter identification, which is not well posed for arbitrary data, is shown to be closely related to the Chebyshev sum inequality. This inequality yields sufficient conditions for existence of feasible solutions both for nonlinear and for linear least-squares problems. The conditions are natural and practical as they are satisfied if the data show the expected monotone and concave behaviour. Copyright © 2007 John Wiley \& Sons, Ltd.}, language = {en}, number = {11}, urldate = {2016-11-13}, journal = {Mathematical Methods in the Applied Sciences}, author = {Hadeler, K. P. and Jukić, Dragan and Sabo, Kristian}, month = jul, year = {2007}, keywords = {Chebyshev sum inequality, existence, Michaelis–Menten kinetics, nonlinear least-squares problem}, pages = {1231--1241}, file = {Hadeler et al (2007) - Least-squares problems for Michaelis–Menten kinetics.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QTXIF2IE\\Hadeler et al (2007) - Least-squares problems for Michaelis–Menten kinetics.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9XEJ77SV\\abstract.html:text/html} } @article{cooling_modular_2016, title = {Modular modelling with {Physiome} standards}, issn = {1469-7793}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/JP272633/abstract}, doi = {10.1113/JP272633}, abstract = {Key points * The complexity of computational models is increasing, supported by research in modelling tools and frameworks. But relatively little thought has gone into design principles for complex models. * We propose a set of design principles for complex model construction with the Physiome standard modelling protocol CellML. * By following the principles, models are generated that are extensible and are themselves suitable for reuse in larger models of increasing complexity. * We illustrate these principles with examples including an architectural prototype linking, for the first time, electrophysiology, thermodynamically compliant metabolism, signal transduction, gene regulation and synthetic biology. * The design principles complement other Physiome research projects, facilitating the application of virtual experiment protocols and model analysis techniques to assist the modelling community in creating libraries of composable, characterised and simulatable quantitative descriptions of physiology. Abstract The ability to produce and customise complex computational models has great potential to have a positive impact on human health. As the field develops towards whole-cell models and linking such models in multi-scale frameworks to encompass tissue, organ, or organism levels, reuse of previous modelling efforts will become increasingly necessary. Any modelling group wishing to reuse existing computational models as modules for their own work faces many challenges in the context of construction, storage, retrieval, documentation and analysis of such modules. Physiome standards, frameworks and tools seek to address several of these challenges, especially for models expressed in the modular protocol CellML. Aside from providing a general ability to produce modules, there has been relatively little research work on architectural principles of CellML models that will enable reuse at larger scales. To complement and support the existing tools and frameworks, we develop a set of principles to address this consideration. The principles are illustrated with examples that couple electrophysiology, signalling, metabolism, gene regulation and synthetic biology, together forming an architectural prototype for whole-cell modelling (including human intervention) in CellML. Such models illustrate how testable units of quantitative biophysical simulation can be constructed. Finally, future relationships between modular models so constructed and Physiome frameworks and tools are discussed, with particular reference to how such frameworks and tools can in turn be extended to complement and gain more benefit from the results of applying the principles.}, language = {en}, urldate = {2016-11-14}, journal = {The Journal of Physiology}, author = {Cooling, Michael T. and Nickerson, David P. and Nielsen, Poul M. F. and Hunter, Peter J.}, month = aug, year = {2016}, keywords = {modelling, modularity, physiome, Standards}, pages = {n/a--n/a}, file = {Cooling et al (2016) - Modular modelling with Physiome standards.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JIJ9CR5U\\Cooling et al (2016) - Modular modelling with Physiome standards.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\HP9MFHVC\\abstract.html:text/html} } @article{breitling_structured_2008, title = {A structured approach for the engineering of biochemical network models, illustrated for signalling pathways}, volume = {9}, issn = {1467-5463, 1477-4054}, url = {http://bib.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/9/5/404}, doi = {10.1093/bib/bbn026}, abstract = {Quantitative models of biochemical networks (signal transduction cascades, metabolic pathways, gene regulatory circuits) are a central component of modern systems biology. Building and managing these complex models is a major challenge that can benefit from the application of formal methods adopted from theoretical computing science. Here we provide a general introduction to the field of formal modelling, which emphasizes the intuitive biochemical basis of the modelling process, but is also accessible for an audience with a background in computing science and/or model engineering. We show how signal transduction cascades can be modelled in a modular fashion, using both a qualitative approach—qualitative Petri nets, and quantitative approaches—continuous Petri nets and ordinary differential equations (ODEs). We review the major elementary building blocks of a cellular signalling model, discuss which critical design decisions have to be made during model building, and present a number of novel computational tools that can help to explore alternative modular models in an easy and intuitive manner. These tools, which are based on Petri net theory, offer convenient ways of composing hierarchical ODE models, and permit a qualitative analysis of their behaviour. We illustrate the central concepts using signal transduction as our main example. The ultimate aim is to introduce a general approach that provides the foundations for a structured formal engineering of large-scale models of biochemical networks.}, language = {en}, number = {5}, urldate = {2016-11-15}, journal = {Briefings in Bioinformatics}, author = {Breitling, Rainer and Gilbert, David and Heiner, Monika and Orton, Richard}, month = sep, year = {2008}, pmid = {18573813}, keywords = {biochemical networks, modelling, ordinary differential equations, Petri nets, signal transduction, Systems Biology}, pages = {404--421}, file = {Breitling et al (2008) - A structured approach for the engineering of biochemical network models,.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JUFBVW38\\Breitling et al (2008) - A structured approach for the engineering of biochemical network models,.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UXC78DS2\\404.html:text/html} } @article{sigg_modeling_2014, title = {Modeling ion channels: {Past}, present, and future}, volume = {144}, copyright = {© 2014 Sigg. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).}, issn = {0022-1295, 1540-7748}, shorttitle = {Modeling ion channels}, url = {http://jgp.rupress.org/content/144/1/7}, doi = {10.1085/jgp.201311130}, abstract = {Ion channels are membrane-bound enzymes whose catalytic sites are ion-conducting pores that open and close (gate) in response to specific environmental stimuli. Ion channels are important contributors to cell signaling and homeostasis. Our current understanding of gating is the product of 60 plus years of voltage-clamp recording augmented by intervention in the form of environmental, chemical, and mutational perturbations. The need for good phenomenological models of gating has evolved in parallel with the sophistication of experimental technique. The goal of modeling is to develop realistic schemes that not only describe data, but also accurately reflect mechanisms of action. This review covers three areas that have contributed to the understanding of ion channels: traditional Eyring kinetic theory, molecular dynamics analysis, and statistical thermodynamics. Although the primary emphasis is on voltage-dependent channels, the methods discussed here are easily generalized to other stimuli and could be applied to any ion channel and indeed any macromolecule.}, language = {en}, number = {1}, urldate = {2016-11-17}, journal = {The Journal of General Physiology}, author = {Sigg, Daniel}, month = jul, year = {2014}, pmid = {24935742}, pages = {7--26}, file = {Sigg (2014) - Modeling ion channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XKPSF2U2\\Sigg (2014) - Modeling ion channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DXQKZCVM\\7.html:text/html} } @article{demir_mathematical_1994, title = {A mathematical model of a rabbit sinoatrial node cell}, volume = {266}, copyright = {Copyright © 1994 the American Physiological Society}, issn = {0363-6143, 1522-1563}, url = {http://ajpcell.physiology.org.ezp.lib.unimelb.edu.au/content/266/3/C832}, abstract = {A mathematical model for the electrophysiological responses of a rabbit sinoatrial node cell that is based on whole cell recordings from enzymatically isolated single pacemaker cells at 37 degrees C has been developed. The ion channels, Na(+)-K+ and Ca2+ pumps, and Na(+)-Ca2+ exchanger in the surface membrane (sarcolemma) are described using equations for these known currents in mammalian pacemaker cells. The extracellular environment is treated as a diffusion-limited space, and the myoplasm contains Ca(2+)-binding proteins (calmodulin and troponin). Original features of this model include 1) new equations for the hyperpolarization-activated inward current, 2) assessment of the role of the transient-type Ca2+ current during pacemaker depolarization, 3) inclusion of an Na+ current based on recent experimental data, and 4) demonstration of the possible influence of pump and exchanger currents and background currents on the pacemaker rate. This model provides acceptable fits to voltage-clamp and action potential data and can be used to seek biophysically based explanations of the electrophysiological activity in the rabbit sinoatrial node cell.}, language = {en}, number = {3}, urldate = {2016-11-18}, journal = {American Journal of Physiology - Cell Physiology}, author = {Demir, S. S. and Clark, J. W. and Murphey, C. R. and Giles, W. R.}, month = mar, year = {1994}, pmid = {8166247}, pages = {C832--C852}, file = {Demir et al (1994) - A mathematical model of a rabbit sinoatrial node cell.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XM2KEATC\\Demir et al (1994) - A mathematical model of a rabbit sinoatrial node cell.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CGJQ9MVN\\C832.html:text/html} } @article{gawthrop_bond_1998, title = {Bond graphs, symbolic algebra and the modelling of complex systems}, volume = {5}, url = {http://citeseerx.ist.psu.edu/viewdoc/download?doi=10.1.1.139.9393&rep=rep1&type=pdf}, number = {6}, urldate = {2016-11-22}, journal = {simulation}, author = {Gawthrop, P. J.}, year = {1998}, pages = {7}, file = {Gawthrop - 1998 - Bond graphs, symbolic algebra and the modelling of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\C4S9BT75\\Gawthrop - 1998 - Bond graphs, symbolic algebra and the modelling of.pdf:application/pdf} } @article{sagar_participatory_2016, title = {Participatory medicine: model based tools for engaging and empowering the individual}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, shorttitle = {Participatory medicine}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150092}, doi = {10.1098/rsfs.2015.0092}, abstract = {The long-term goal of the Virtual Physiological Human and Digital Patient projects is to run 'simulations’ of health and disease processes on the virtual or 'digital' patient, and use the results to make predictions about real health and determine the best treatment specifically for an individual. This is termed 'personalized medicine', and is intended to be the future of healthcare. How will people interact and engage with their virtual selves, and how can virtual models be used to motivate people to actively participate in their own healthcare? We discuss these questions, and describe our current efforts to integrate and realistically embody psychobiological models of face-to-face interaction to enliven and increase engagement of virtual humans in healthcare. Overall, this paper highlights the need for attention to the design of human–machine interfaces to address patient engagement in healthcare.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Sagar, Mark and Broadbent, Elizabeth}, month = apr, year = {2016}, pages = {20150092}, file = {Sagar_Broadbent (2016) - Participatory medicine.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\63G9C2CT\\Sagar_Broadbent (2016) - Participatory medicine.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\TAAWFCQU\\20150092.html:text/html} } @article{beek_understanding_2016, title = {Understanding the physiology of the ageing individual: computational modelling of changes in metabolism and endurance}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, shorttitle = {Understanding the physiology of the ageing individual}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150079}, doi = {10.1098/rsfs.2015.0079}, abstract = {Ageing and lifespan are strongly affected by metabolism. The maximal possible uptake of oxygen is not only a good predictor of performance in endurance sports, but also of life expectancy. Figuratively speaking, healthy ageing is a competitive sport. Although the root cause of ageing is damage to macromolecules, it is the balance with repair processes that is decisive. Reduced or intermittent nutrition, hormones and intracellular signalling pathways that regulate metabolism have strong effects on ageing. Homeostatic regulatory processes tend to keep the environment of the cells within relatively narrow bounds. On the other hand, the body is constantly adapting to physical activity and food consumption. Spontaneous fluctuations in heart rate and other processes indicate youth and health. A (homeo)dynamic aspect of homeostasis deteriorates with age. We are now in a position to develop computational models of human metabolism and the dynamics of heart rhythm and oxygen transport that will advance our understanding of ageing. Computational modelling of the connections between dietary restriction, metabolism and protein turnover may increase insight into homeostasis of the proteins in our body. In this way, the computational reconstruction of human physiological processes, the Physiome, can help prevent frailty and age-related disease.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Beek, Johannes H. G. M. van and Kirkwood, Thomas B. L. and Bassingthwaighte, James B.}, month = apr, year = {2016}, pages = {20150079}, file = {Beek et al (2016) - Understanding the physiology of the ageing individual.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\U54FFUSQ\\Beek et al (2016) - Understanding the physiology of the ageing individual.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EERNVQ5E\\20150079.html:text/html} } @article{castro_mathematics_2016, title = {Mathematics in modern immunology}, volume = {6}, copyright = {© 2016 The Authors.. http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.}, issn = {2042-8898, 2042-8901}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150093}, doi = {10.1098/rsfs.2015.0093}, abstract = {Mathematical and statistical methods enable multidisciplinary approaches that catalyse discovery. Together with experimental methods, they identify key hypotheses, define measurable observables and reconcile disparate results. We collect a representative sample of studies in T-cell biology that illustrate the benefits of modelling–experimental collaborations and that have proven valuable or even groundbreaking. We conclude that it is possible to find excellent examples of synergy between mathematical modelling and experiment in immunology, which have brought significant insight that would not be available without these collaborations, but that much remains to be discovered.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Castro, Mario and Lythe, Grant and Molina-París, Carmen and Ribeiro, Ruy M.}, month = apr, year = {2016}, pages = {20150093}, file = {Castro et al (2016) - Mathematics in modern immunology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NG5XNIJB\\Castro et al (2016) - Mathematics in modern immunology.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4BIP4MHV\\20150093.html:text/html} } @article{vinnakota_improving_2016, title = {Improving the physiological realism of experimental models}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150076}, doi = {10.1098/rsfs.2015.0076}, abstract = {The Virtual Physiological Human (VPH) project aims to develop integrative, explanatory and predictive computational models (C-Models) as numerical investigational tools to study disease, identify and design effective therapies and provide an in silico platform for drug screening. Ultimately, these models rely on the analysis and integration of experimental data. As such, the success of VPH depends on the availability of physiologically realistic experimental models (E-Models) of human organ function that can be parametrized to test the numerical models. Here, the current state of suitable E-models, ranging from in vitro non-human cell organelles to in vivo human organ systems, is discussed. Specifically, challenges and recent progress in improving the physiological realism of E-models that may benefit the VPH project are highlighted and discussed using examples from the field of research on cardiovascular disease, musculoskeletal disorders, diabetes and Parkinson's disease.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Vinnakota, Kalyan C. and Cha, Chae Y. and Rorsman, Patrik and Balaban, Robert S. and Gerche, Andre La and Wade-Martins, Richard and Beard, Daniel A. and Jeneson, Jeroen A. L.}, month = apr, year = {2016}, pages = {20150076}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R7IAXDAU\\20150076.html:text/html;Vinnakota et al (2016) - Improving the physiological realism of experimental models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DUJIKUIN\\Vinnakota et al (2016) - Improving the physiological realism of experimental models.pdf:application/pdf} } @article{geris_silico_2016, title = {In silico regenerative medicine: how computational tools allow regulatory and financial challenges to be addressed in a volatile market}, volume = {6}, copyright = {© 2016 The Authors.. http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.}, issn = {2042-8898, 2042-8901}, shorttitle = {In silico regenerative medicine}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150105}, doi = {10.1098/rsfs.2015.0105}, abstract = {The cell therapy market is a highly volatile one, due to the use of disruptive technologies, the current economic situation and the small size of the market. In such a market, companies as well as academic research institutes are in need of tools to advance their understanding and, at the same time, reduce their R\&D costs, increase product quality and productivity, and reduce the time to market. An additional difficulty is the regulatory path that needs to be followed, which is challenging in the case of cell-based therapeutic products and should rely on the implementation of quality by design (QbD) principles. In silico modelling is a tool that allows the above-mentioned challenges to be addressed in the field of regenerative medicine. This review discusses such in silico models and focuses more specifically on the bioprocess. Three (clusters of) examples related to this subject are discussed. The first example comes from the pharmaceutical engineering field where QbD principles and their implementation through the use of in silico models are both a regulatory and economic necessity. The second example is related to the production of red blood cells. The described in silico model is mainly used to investigate the manufacturing process of the cell-therapeutic product, and pays special attention to the economic viability of the process. Finally, we describe the set-up of a model capturing essential events in the development of a tissue-engineered combination product in the context of bone tissue engineering. For each of the examples, a short introduction to some economic aspects is given, followed by a description of the in silico tool or tools that have been developed to allow the implementation of QbD principles and optimal design.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Geris, L. and Guyot, Y. and Schrooten, J. and Papantoniou, I.}, month = apr, year = {2016}, pages = {20150105}, file = {Geris et al (2016) - In silico regenerative medicine.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QI8B32DS\\Geris et al (2016) - In silico regenerative medicine.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EWJAC593\\20150105.html:text/html} } @article{nyman_requirements_2016, title = {Requirements for multi-level systems pharmacology models to reach end-usage: the case of type 2 diabetes}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, shorttitle = {Requirements for multi-level systems pharmacology models to reach end-usage}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150075}, doi = {10.1098/rsfs.2015.0075}, abstract = {We are currently in the middle of a major shift in biomedical research: unprecedented and rapidly growing amounts of data may be obtained today, from in vitro, in vivo and clinical studies, at molecular, physiological and clinical levels. To make use of these large-scale, multi-level datasets, corresponding multi-level mathematical models are needed, i.e. models that simultaneously capture multiple layers of the biological, physiological and disease-level organization (also referred to as quantitative systems pharmacology—QSP—models). However, today's multi-level models are not yet embedded in end-usage applications, neither in drug research and development nor in the clinic. Given the expectations and claims made historically, this seemingly slow adoption may seem surprising. Therefore, we herein consider a specific example—type 2 diabetes—and critically review the current status and identify key remaining steps for these models to become mainstream in the future. This overview reveals how, today, we may use models to ask scientific questions concerning, e.g., the cellular origin of insulin resistance, and how this translates to the whole-body level and short-term meal responses. However, before these multi-level models can become truly useful, they need to be linked with the capabilities of other important existing models, in order to make them ‘personalized’ (e.g. specific to certain patient phenotypes) and capable of describing long-term disease progression. To be useful in drug development, it is also critical that the developed models and their underlying data and assumptions are easily accessible. For clinical end-usage, in addition, model links to decision-support systems combined with the engagement of other disciplines are needed to create user-friendly and cost-efficient software packages.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Nyman, Elin and Rozendaal, Yvonne J. W. and Helmlinger, Gabriel and Hamrén, Bengt and Kjellsson, Maria C. and Strålfors, Peter and Riel, Natal A. W. van and Gennemark, Peter and Cedersund, Gunnar}, month = apr, year = {2016}, pages = {20150075}, file = {Nyman et al (2016) - Requirements for multi-level systems pharmacology models to reach end-usage.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GNIFHK2B\\Nyman et al (2016) - Requirements for multi-level systems pharmacology models to reach end-usage.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EA42PKQV\\20150075.html:text/html} } @article{bono_requirements_2016, title = {Requirements for the formal representation of pathophysiology mechanisms by clinicians}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150099}, doi = {10.1098/rsfs.2015.0099}, abstract = {Knowledge of multiscale mechanisms in pathophysiology is the bedrock of clinical practice. If quantitative methods, predicting patient-specific behaviour of these pathophysiology mechanisms, are to be brought to bear on clinical decision-making, the Human Physiome community and Clinical community must share a common computational blueprint for pathophysiology mechanisms. A number of obstacles stand in the way of this sharing—not least the technical and operational challenges that must be overcome to ensure that (i) the explicit biological meanings of the Physiome's quantitative methods to represent mechanisms are open to articulation, verification and study by clinicians, and that (ii) clinicians are given the tools and training to explicitly express disease manifestations in direct contribution to modelling. To this end, the Physiome and Clinical communities must co-develop a common computational toolkit, based on this blueprint, to bridge the representation of knowledge of pathophysiology mechanisms (a) that is implicitly depicted in electronic health records and the literature, with (b) that found in mathematical models explicitly describing mechanisms. In particular, this paper makes use of a step-wise description of a specific disease mechanism as a means to elicit the requirements of representing pathophysiological meaning explicitly. The computational blueprint developed from these requirements addresses the Clinical community goals to (i) organize and manage healthcare resources in terms of relevant disease-related knowledge of mechanisms and (ii) train the next generation of physicians in the application of quantitative methods relevant to their research and practice.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Bono, B. de and Helvensteijn, M. and Kokash, N. and Martorelli, I. and Sarwar, D. and Islam, S. and Grenon, P. and Hunter, P.}, month = apr, year = {2016}, pages = {20150099}, file = {Bono et al (2016) - Requirements for the formal representation of pathophysiology mechanisms by.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\F7QWR6RW\\Bono et al (2016) - Requirements for the formal representation of pathophysiology mechanisms by.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9M4H89RS\\20150099.html:text/html} } @article{chabiniok_multiphysics_2016, title = {Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic: ventricular cardiac mechanics}, volume = {6}, copyright = {© 2016 The Authors.. http://creativecommons.org/licenses/by/4.0/Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.}, issn = {2042-8898, 2042-8901}, shorttitle = {Multiphysics and multiscale modelling, data–model fusion and integration of organ physiology in the clinic}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150083}, doi = {10.1098/rsfs.2015.0083}, abstract = {With heart and cardiovascular diseases continually challenging healthcare systems worldwide, translating basic research on cardiac (patho)physiology into clinical care is essential. Exacerbating this already extensive challenge is the complexity of the heart, relying on its hierarchical structure and function to maintain cardiovascular flow. Computational modelling has been proposed and actively pursued as a tool for accelerating research and translation. Allowing exploration of the relationships between physics, multiscale mechanisms and function, computational modelling provides a platform for improving our understanding of the heart. Further integration of experimental and clinical data through data assimilation and parameter estimation techniques is bringing computational models closer to use in routine clinical practice. This article reviews developments in computational cardiac modelling and how their integration with medical imaging data is providing new pathways for translational cardiac modelling.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Chabiniok, Radomir and Wang, Vicky Y. and Hadjicharalambous, Myrianthi and Asner, Liya and Lee, Jack and Sermesant, Maxime and Kuhl, Ellen and Young, Alistair A. and Moireau, Philippe and Nash, Martyn P. and Chapelle, Dominique and Nordsletten, David A.}, month = apr, year = {2016}, pages = {20150083}, file = {Chabiniok et al (2016) - Multiphysics and multiscale modelling, data–model fusion and integration of.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DDJF8JV7\\Chabiniok et al (2016) - Multiphysics and multiscale modelling, data–model fusion and integration of.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V757CF9B\\20150083.html:text/html} } @article{fernandez_multiscale_2016, title = {Multiscale musculoskeletal modelling, data–model fusion and electromyography-informed modelling}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150084}, doi = {10.1098/rsfs.2015.0084}, abstract = {This paper proposes methods and technologies that advance the state of the art for modelling the musculoskeletal system across the spatial and temporal scales; and storing these using efficient ontologies and tools. We present population-based modelling as an efficient method to rapidly generate individual morphology from only a few measurements and to learn from the ever-increasing supply of imaging data available. We present multiscale methods for continuum muscle and bone models; and efficient mechanostatistical methods, both continuum and particle-based, to bridge the scales. Finally, we examine both the importance that muscles play in bone remodelling stimuli and the latest muscle force prediction methods that use electromyography-assisted modelling techniques to compute musculoskeletal forces that best reflect the underlying neuromuscular activity. Our proposal is that, in order to have a clinically relevant virtual physiological human, (i) bone and muscle mechanics must be considered together; (ii) models should be trained on population data to permit rapid generation and use underlying principal modes that describe both muscle patterns and morphology; and (iii) these tools need to be available in an open-source repository so that the scientific community may use, personalize and contribute to the database of models.}, language = {en}, number = {2}, urldate = {2016-11-28}, journal = {Interface Focus}, author = {Fernandez, J. and Zhang, J. and Heidlauf, T. and Sartori, M. and Besier, T. and Röhrle, O. and Lloyd, D.}, month = apr, year = {2016}, pages = {20150084}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AEDKEMWV\\20150084.html:text/html} } @article{thomas_physiome_2016, title = {A physiome interoperability roadmap for personalized drug development}, volume = {6}, copyright = {© 2016 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {2042-8898, 2042-8901}, url = {http://rsfs.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/6/2/20150094}, doi = {10.1098/rsfs.2015.0094}, abstract = {The goal of developing therapies and dosage regimes for characterized subgroups of the general population can be facilitated by the use of simulation models able to incorporate information about inter-individual variability in drug disposition (pharmacokinetics), toxicity and response effect (pharmacodynamics). Such observed variability can have multiple causes at various scales, ranging from gross anatomical differences to differences in genome sequence. Relevant data for many of these aspects, particularly related to molecular assays (known as ‘-omics’), are available in online resources, but identification and assignment to appropriate model variables and parameters is a significant bottleneck in the model development process. Through its efforts to standardize annotation with consequent increase in data usability, the human physiome project has a vital role in improving productivity in model development and, thus, the development of personalized therapy regimes. Here, we review the current status of personalized medicine in clinical practice, outline some of the challenges that must be overcome in order to expand its applicability, and discuss the relevance of personalized medicine to the more widespread challenges being faced in drug discovery and development. We then review some of (i) the key data resources available for use in model development and (ii) the potential areas where advances made within the physiome modelling community could contribute to physiologically based pharmacokinetic and physiologically based pharmacokinetic/pharmacodynamic modelling in support of personalized drug development. We conclude by proposing a roadmap to further guide the physiome community in its on-going efforts to improve data usability, and integration with modelling efforts in the support of personalized medicine development.}, language = {en}, number = {2}, urldate = {2016-11-29}, journal = {Interface Focus}, author = {Thomas, Simon and Wolstencroft, Katherine and Bono, Bernard de and Hunter, Peter J.}, month = apr, year = {2016}, pages = {20150094}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UX3DZCPK\\20150094.html:text/html;Thomas et al (2016) - A physiome interoperability roadmap for personalized drug development.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XJ489ZUH\\Thomas et al (2016) - A physiome interoperability roadmap for personalized drug development.pdf:application/pdf} } @article{schuster_what_1995, title = {What {Information} about the {Conserved}-{Moiety} {Structure} of {Chemical} {Reaction} {Systems} {Can} be {Derived} from {Their} {Stoichiometry}?}, volume = {99}, issn = {0022-3654}, url = {http://dx.doi.org/10.1021/j100020a026}, doi = {10.1021/j100020a026}, number = {20}, urldate = {2016-12-01}, journal = {The Journal of Physical Chemistry}, author = {Schuster, Stefan and Hilgetag, Claus}, month = may, year = {1995}, pages = {8017--8023}, file = {ACS Full Text Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\XXF2PHED\\j100020a026.html:text/html;Schuster_Hilgetag (1995) - What Information about the Conserved-Moiety Structure of Chemical Reaction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GSD7BH47\\Schuster_Hilgetag (1995) - What Information about the Conserved-Moiety Structure of Chemical Reaction.pdf:application/pdf} } @article{hunter_virtual_2016, title = {The {Virtual} {Physiological} {Human}: {The} {Physiome} {Project} {Aims} to {Develop} {Reproducible}, {Multiscale} {Models} for {Clinical} {Practice}}, volume = {7}, issn = {2154-2287}, shorttitle = {The {Virtual} {Physiological} {Human}}, doi = {10.1109/MPUL.2016.2563841}, abstract = {The Physiome Project was initiated by the International Union of Physiological Sciences (IUPS; www.iups.org) in 1997 to bring multiscale engineering modeling approaches to the physiological interpretation of the wealth of molecular data that was becoming available at that time [1]. The discipline of physiology, which with anatomy underpins medical practice, had lost its traditional central position in the biological sciences (at least from a funding perspective) to molecular biology, despite the very small impact molecular biology has had on the diagnosis and treatment of disease. While diseases and drugs certainly operate at the molecular level, the regulation of genetic transcription and, hence, the expression of proteins (the building blocks of life) are both highly dependent on environmental factors governed by the physical world in which molecular biology operates. Engineering-in particular, the rapidly growing field of bioengineering-is the discipline that has the integrative skills and tools to put the molecular pieces of Humpty Dumpty back together again.}, number = {4}, journal = {IEEE Pulse}, author = {Hunter, P.}, month = jul, year = {2016}, keywords = {anatomy underpin medical practice, Biological system modeling, diseases, Drugs, Genetics, genetic transcription, Mathematical model, Molecular biology, molecular biophysics, molecular level, multiscale engineering modeling, patient diagnosis, patient treatment, physiological interpretation, Physiology, physiome project, protein expression, Proteins, virtual physiological human}, pages = {36--42}, file = {Hunter (2016) - The Virtual Physiological Human.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8XIGB76J\\Hunter (2016) - The Virtual Physiological Human.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UHIBDBQ6\\7509697.html:text/html} } @article{cooling_modelling_2008, title = {Modelling biological modularity with {CellML}}, volume = {2}, issn = {1751-8849}, doi = {10.1049/iet-syb:20070020}, abstract = {In recent years advances in the construction of mathematical models of biological systems have yielded an array of valuable constructs. The authors seek to provide a 'leading practice' method for implementing modularised kinetic mass-action models in order to obtain a number of advantages in model construction, validation and derived insights. The authors advocate the consideration of 'accounting cycles' or 'chains' to define 'functional' components and the separate consideration of 'messenger' components for mobile or diffusive molecular species. From a conceptual modularisation the authors illustrate, with an example drawn from signal transduction, a component- based formulation in the model exchange format cellular modelling markup language (CellML) 1.1 - demonstrating loose coupling between functionally-focused reusable components. Finally, the authors discuss the dilemmas associated with modelling protein-to-protein interactions, and the vision for using future CellML enhancements to resolve potential duplications when combining independently developed models.}, number = {2}, journal = {IET Systems Biology}, author = {Cooling, M. T. and Hunter, P. and Crampin, E. J.}, month = mar, year = {2008}, keywords = {biological modularity, biology computing, CellML modelling, cellular biophysics, cellular modelling markup language, modularised kinetic mass-action models, physiological models, signal transduction}, pages = {73--79}, file = {Cooling et al (2008) - Modelling biological modularity with CellML.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2MFU2KGJ\\Cooling et al (2008) - Modelling biological modularity with CellML.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DNIS9PP8\\4483541.html:text/html} } @article{gracia_mass_2006, title = {Mass and charge conservation check in dynamic models: application to the new {ADM}1 model}, volume = {53}, copyright = {© IWA Publishing 2006}, issn = {0273-1223, 1996-9732}, shorttitle = {Mass and charge conservation check in dynamic models}, url = {http://wst.iwaponline.com/content/53/1/225}, doi = {10.2166/wst.2006.025}, abstract = {Skip to Next Section This paper proposes a systematic methodology for the analysis of the mass and charge balances in dynamic models expressed using the Petersen matrix notation. This methodology is based on the definition of the model components via elemental mass fractions and in the estimation of the COD as a function of the redox equations associated with these elements. This approach makes the automatic calculation of all the stoichiometric coefficients under different measuring units and the study of COD, charge or mass fluxes easier. As an example of its application this methodology was applied to the ADM1 in order to illustrate its usefulness for the analysis of organic matter characterisation, nitrogen release or biogas composition in anaerobic digestion. The application of the methodology for a rigorous integration of different IWA models is proposed for further study.}, language = {en}, number = {1}, urldate = {2016-12-06}, journal = {Water Science and Technology}, author = {Gracia, M. de and Sancho, L. and García-Heras, J. L. and Vanrolleghem, P. and Ayesa, E.}, month = jan, year = {2006}, pages = {225--240}, file = {Gracia et al (2006) - Mass and charge conservation check in dynamic models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZDKSJ9SN\\Gracia et al (2006) - Mass and charge conservation check in dynamic models.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KDVB3HUS\\225.html:text/html} } @article{gevorgyan_detection_2008, title = {Detection of stoichiometric inconsistencies in biomolecular models}, volume = {24}, issn = {1367-4803, 1460-2059}, url = {http://bioinformatics.oxfordjournals.org.ezp.lib.unimelb.edu.au/content/24/19/2245}, doi = {10.1093/bioinformatics/btn425}, abstract = {Motivation: Metabolic modelling provides a mathematically rigorous basis for system-level analysis of biochemical networks. However, the growing sizes of metabolic models can lead to serious problems in their construction and validation. In this work, we describe a relatively poorly investigated type of modelling error, called stoichiometric inconsistencies. These errors are caused by incorrect definitions of reaction stoichiometries and result in conflicts between two fundamental physical constraints to be satisfied by any valid metabolic model: positivity of molecular masses of all metabolites and mass conservation in all interconversions. Results: We introduce formal definitions of stoichiometric inconsistencies, inconsistent net stoichiometries, elementary leakage modes and other important fundamental properties of incorrectly defined biomolecular networks. Algorithms are described for the verification of stoichiometric consistency of a model, detection of unconserved metabolites and inconsistent minimal net stoichiometries. The usefulness of these algorithms for effective resolving of inconsistencies and for detection of input errors is demonstrated on a published genome-scale metabolic model of Saccharomyces cerevisiae and one of Streptococcus agalactiae constructed using the KEGG database. Availability: http://mudshark.brookes.ac.uk/index.php/Albert\_Gevorgyan Contact:dfell@brookes.ac.uk}, language = {en}, number = {19}, urldate = {2016-12-08}, journal = {Bioinformatics}, author = {Gevorgyan, Albert and Poolman, Mark G. and Fell, David A.}, month = oct, year = {2008}, pmid = {18697772}, pages = {2245--2251}, file = {Gevorgyan et al (2008) - Detection of stoichiometric inconsistencies in biomolecular models.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AEUTIZMS\\Gevorgyan et al (2008) - Detection of stoichiometric inconsistencies in biomolecular models.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7BUNGWMR\\2245.html:text/html} } @article{marashi_mathematical_2014, title = {A mathematical approach to emergent properties of metabolic networks: {Partial} coupling relations, hyperarcs and flux ratios}, volume = {355}, issn = {0022-5193}, shorttitle = {A mathematical approach to emergent properties of metabolic networks}, url = {http://www.sciencedirect.com/science/article/pii/S0022519314002318}, doi = {10.1016/j.jtbi.2014.04.011}, abstract = {Emergent properties in systems biology are those which arise only when the biological system passes a certain level of complexity. In this study, we introduce some of the emergent properties which appear in the constraint-based analysis of metabolic networks. These properties generally appear as a result of existence of hfdeyperarcs and irreversible reactions in networks. Here, we present examples of metabolic networks in which there exist at least two reactions whose fluxes cannot be written as products and/or ratios of the stoichiometric coefficients of the network. We show that any such network contains at least one hyperarc. Additionally, we prove that partial coupling cannot appear in consistent metabolic networks with less than four reactions, or with less than three irreversible reactions, or without hyperarc(s).}, urldate = {2016-12-11}, journal = {Journal of Theoretical Biology}, author = {Marashi, Sayed-Amir and Tefagh, Mojtaba}, month = aug, year = {2014}, keywords = {Emergence, FCA, Flow networks, Flux coupling analysis, Hypergraph}, pages = {185--193}, file = {Marashi_Tefagh (2014) - A mathematical approach to emergent properties of metabolic networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CZURJTXD\\Marashi_Tefagh (2014) - A mathematical approach to emergent properties of metabolic networks.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ENTVV2FJ\\S0022519314002318.html:text/html} } @book{bers_excitation-contraction_2001, address = {Dordrecht}, series = {Developments in {Cardiovascular} {Medicine}}, title = {Excitation-{Contraction} {Coupling} and {Cardiac} {Contractile} {Force}}, volume = {237}, isbn = {978-0-7923-7158-8 978-94-010-0658-3}, url = {http://link.springer.com/10.1007/978-94-010-0658-3}, urldate = {2016-12-13}, publisher = {Springer Netherlands}, author = {Bers, Donald M.}, year = {2001}, file = {Bers (2001) - Excitation-Contraction Coupling and Cardiac Contractile Force.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D5B85EBX\\Bers (2001) - Excitation-Contraction Coupling and Cardiac Contractile Force.pdf:application/pdf} } @article{bers_sarcoplasmic_2003-1, title = {Sarcoplasmic {Reticulum} {Ca}2+ and {Heart} {Failure}}, volume = {93}, copyright = {© 2003}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org/content/93/6/487}, doi = {10.1161/01.RES.0000091871.54907.6B}, abstract = {Heart failure (HF) is a leading cause of death and enormous effort has focused at understanding the molecular and cellular mechanisms of the decreased cardiac contractility. While changes of other components contribute, it is generally agreed that much of the contractile deficit is due to reduced myocyte Ca2+ transients.1,2 Alterations in Ca2+ current ( I Ca) and action potential characteristics are also seen in HF, but a central factor limiting Ca2+ transient amplitude is a decrease of sarcoplasmic reticulum (SR) Ca2+ content.3–6 HF is extremely complex, but it is easy to appreciate how reduced SR Ca2+ content would reduce SR Ca2+ release, myofilament activation, and contractility. Despite agreement that SR Ca2+ content is reduced in HF, controversy exists about why SR content is low. SR Ca2+ content reflects the balance between Ca2+ uptake (via SERCA) and Ca2+ efflux via ryanodine receptor (RyR). Thus, reduced SR content in HF must be due to reduced Ca2+ pumping by SERCA or increased SR Ca2+ leak via RyRs. Both are supported by experimental data (below). Transsarcolemmal Ca2+ fluxes also affect SR Ca2+ load. That is, reduced Ca2+ influx (eg, via I Ca) or enhanced Ca2+ extrusion via Na+-Ca2+ exchange (NCX) can unload the SR. Results are not unanimous, but most groups find little alteration in peak I Ca density in HF, while many find evidence of enhanced NCX expression and function.1,2 Increased NCX function can compete with SERCA during [Ca2+]i decline, extruding more Ca2+ from the cell and depleting the SR. In the new steady state, a larger fraction of activating Ca2+ also enters the cell at each beat in HF (eg, smaller Ca2+ release causes less …}, language = {en}, number = {6}, urldate = {2016-12-14}, journal = {Circulation Research}, author = {Bers, Donald M. and Eisner, David A. and Valdivia, Héctor H.}, month = sep, year = {2003}, pmid = {14500331}, keywords = {calcium sparks, heart failure, ryanodine receptors}, pages = {487--490}, file = {Bers et al (2003) - Sarcoplasmic Reticulum Ca2+ and Heart Failure.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\99TAEX4J\\Bers et al (2003) - Sarcoplasmic Reticulum Ca2+ and Heart Failure.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7ZRI6R52\\487.html:text/html} } @article{noble_models_2001, title = {Models of cardiac ventricular action potentials: iterative interaction between experiment and simulation}, volume = {359}, issn = {1364-503X, 1471-2962}, shorttitle = {Models of cardiac ventricular action potentials}, url = {http://rsta.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/359/1783/1127}, doi = {10.1098/rsta.2001.0820}, abstract = {The development of cardiac ventricular cell models since 1960 is reviewed with the focus on the interaction between simulation and experimental work. At each stage, the reasons for new models are explained, as are their defects and how these were used to point the way to successor models. A key feature of our analysis is the demonstration that as much, if not more, was learnt from the way in which models failed as from their successes. The review leads up to the most recent developments in this field and indicates the ways in which it may be expected to advance in the future.}, language = {en}, number = {1783}, urldate = {2017-01-17}, journal = {Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and Engineering Sciences}, author = {Noble, D. and Rudy, Y.}, month = jun, year = {2001}, pages = {1127--1142}, file = {Noble and Rudy - 2001 - Models of cardiac ventricular action potentials i.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6AJMUMAP\\Noble and Rudy - 2001 - Models of cardiac ventricular action potentials i.pdf:application/pdf} } @article{gawthrop_bond_2015, title = {Bond {Graph} {Modelling} of {Chemoelectrical} {Energy} {Transduction}: {The} {Energetic} {Cost} of the {Action} {Potential}}, shorttitle = {Bond {Graph} {Modelling} of {Chemoelectrical} {Energy} {Transduction}}, url = {http://arxiv.org/abs/1512.00956}, abstract = {Energy-based bond graph modelling of biomolecular systems is extended to include chemoelectrical trans- duction thus enabling integrated thermodynamically-compliant modelling of chemoelectrical systems in general and excitable membranes in particular. Our general approach is illustrated by recreating a well-known model of an excitable membrane. This model is used to investigate the energy consumed during a membrane action potential thus contributing to the current debate on the trade-off between the speed of an action potential event and energy consumption. The influx of Na+ is often taken as a proxy for energy consumption; in contrast, this paper presents an energy based model of action potentials. As the energy based approach avoids the assumptions underlying the proxy approach it can be directly used to compute energy consumption in both healthy and diseased neurons. These results are illustrated by comparing the energy consumption of healthy and degenerative retinal ganglion cells using both simulated and in vitro data.}, urldate = {2017-02-02}, journal = {arXiv:1512.00956 [physics, q-bio]}, author = {Gawthrop, Peter J. and Siekmann, Ivo and Kameneva, Tatiana and Saha, Susmita and Ibbotson, Michael R. and Crampin, Edmund J.}, month = dec, year = {2015}, note = {arXiv: 1512.00956}, keywords = {Physics - Biological Physics, Quantitative Biology - Quantitative Methods}, file = {Gawthrop et al (2015) - Bond Graph Modelling of Chemoelectrical Energy Transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AFATBGXN\\Gawthrop et al (2015) - Bond Graph Modelling of Chemoelectrical Energy Transduction.pdf:application/pdf} } @article{luo_model_1991, title = {A model of the ventricular cardiac action potential. {Depolarization}, repolarization, and their interaction.}, volume = {68}, copyright = {Copyright © 1991 by American Heart Association}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/68/6/1501}, doi = {10.1161/01.RES.68.6.1501}, abstract = {A mathematical model of the membrane action potential of the mammalian ventricular cell is introduced. The model is based, whenever possible, on recent single-cell and single-channel data and incorporates the possibility of changing extracellular potassium concentration [K]o. The fast sodium current, INa, is characterized by fast upstroke velocity (Vmax = 400 V/sec) and slow recovery from inactivation. The time-independent potassium current, IK1, includes a negative-slope phase and displays significant crossover phenomenon as [K]o is varied. The time-dependent potassium current, IK, shows only a minimal degree of crossover. A novel potassium current that activates at plateau potentials is included in the model. The simulated action potential duplicates the experimentally observed effects of changes in [K]o on action potential duration and rest potential. Physiological simulations focus on the interaction between depolarization and repolarization (i.e., premature stimulation). Results demonstrate the importance of the slow recovery of INa in determining the response of the cell. Simulated responses to periodic stimulation include monotonic Wenckebach patterns and alternans at normal [K]o, whereas at low [K]o nonmonotonic Wenckebach periodicities, aperiodic patterns, and enhanced supernormal excitability that results in unstable responses ("chaotic activity") are observed. The results are consistent with recent experimental observations, and the model simulations relate these phenomena to the underlying ionic channel kinetics.}, language = {en}, number = {6}, urldate = {2017-02-06}, journal = {Circulation Research}, author = {Luo, C. H. and Rudy, Y.}, month = jun, year = {1991}, pmid = {1709839}, pages = {1501--1526}, file = {Luo_Rudy (1991) - A model of the ventricular cardiac action potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\84INDJGZ\\Luo_Rudy (1991) - A model of the ventricular cardiac action potential.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\I8DH3KDQ\\1501.html:text/html} } @article{chua_hodgkin-huxley_2012, title = {Hodgkin-{Huxley} axon is made of memristors}, volume = {22}, issn = {0218-1274, 1793-6551}, url = {http://www.worldscientific.com/doi/abs/10.1142/S021812741230011X}, doi = {10.1142/S021812741230011X}, language = {en}, number = {03}, urldate = {2017-02-14}, journal = {International Journal of Bifurcation and Chaos}, author = {Chua, Leon and Sbitnev, Valery and Kim, Hyongsuk}, month = mar, year = {2012}, pages = {1230011}, file = {ChuSbiKim12.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\J4BNM99U\\ChuSbiKim12.pdf:application/pdf} } @article{makielski_sodium_1987, title = {Sodium current in voltage clamped internally perfused canine cardiac {Purkinje} cells}, volume = {52}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S000634958783182X}, doi = {10.1016/S0006-3495(87)83182-X}, abstract = {Study of the excitatory sodium current (INa) intact heart muscle has been hampered by the limitations of voltage clamp methods in multicellular preparations that result from the presence of large series resistance and from extracellular ion accumulation and depletion. To minimize these problems we voltage clamped and internally perfused freshly isolated canine cardiac Purkinje cells using a large bore (25-microns diam) double-barreled flow-through glass suction pipette. Control of [Na+]i was demonstrated by the agreement of measured INa reversal potentials with the predictions of the Nernst relation. Series resistance measured by an independent microelectrode was comparable to values obtained in voltage clamp studies of squid axons (less than 3.0 omega-cm2). The rapid capacity transient decays (tau c less than 15 microseconds) and small deviations of membrane potential (less than 4 mV at peak INa) achieved in these experiments represent good conditions for the study of INa. We studied INa in 26 cells (temperature range 13 degrees-24 degrees C) with 120 or 45 mM [Na+]o and 15 mM [Na+]i. Time to peak INa at 18 degrees C ranged from 1.0 ms (-40 mV) to less than 250 microseconds (+ 40 mV), and INa decayed with a time course best described by two time constants in the voltage range -60 to -10 mV. Normalized peak INa in eight cells at 18 degrees C was 2.0 +/- 0.2 mA/cm2 with [Na+]o 45 mM and 4.1 +/- 0.6 mA/cm2 with [Na+]o 120 mM. These large peak current measurements require a high density of Na+ channels. It is estimated that 67 +/- 6 channels/micron 2 are open at peak INa, and from integrated INa as many as 260 Na+ channels/micron2 are available for opening in canine cardiac Purkinje cells.}, number = {1}, urldate = {2017-02-20}, journal = {Biophysical Journal}, author = {Makielski, J. C. and Sheets, M. F. and Hanck, D. A. and January, C. T. and Fozzard, H. A.}, month = jul, year = {1987}, pages = {1--11}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\F26FG35P\\S000634958783182X.html:text/html} } @article{sula_complete_2017, title = {The complete structure of an activated open sodium channel}, volume = {8}, copyright = {© 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved.}, issn = {2041-1723}, url = {http://www.nature.com.ezp.lib.unimelb.edu.au/ncomms/2017/170216/ncomms14205/full/ncomms14205.html}, doi = {10.1038/ncomms14205}, abstract = {Voltage-gated sodium (Nav) channels are crucial for action potential initiation in excitable cells. Here the authors present the complete structure of prokaryotic NavMs in a fully open state, providing structural insight into the opening and closure of the channel\&\#39;s intracellular gate.}, language = {en}, urldate = {2017-02-22}, journal = {Nature Communications}, author = {Sula, Altin and Booker, Jennifer and Ng, Leo C. T. and Naylor, Claire E. and DeCaen, Paul G. and Wallace, B. A.}, month = feb, year = {2017}, pages = {14205}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SFHV987H\\ncomms14205.html:text/html;Sula et al (2017) - The complete structure of an activated open sodium channel.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6MWEM65C\\Sula et al (2017) - The complete structure of an activated open sodium channel.pdf:application/pdf} } @article{zhu_reduction_2011, title = {Reduction in number of sarcolemmal {KATP} channels slows cardiac action potential duration shortening under hypoxia}, volume = {415}, issn = {0006-291X}, url = {http://www.sciencedirect.com/science/article/pii/S0006291X11019590}, doi = {10.1016/j.bbrc.2011.10.125}, abstract = {The cardiovascular system operates under demands ranging from conditions of rest to extreme stress. One mechanism of cardiac stress tolerance is action potential duration shortening driven by ATP-sensitive potassium (KATP) channels. KATP channel expression has a significant physiologic impact on action potential duration shortening and myocardial energy consumption in response to physiologic heart rate acceleration. However, the effect of reduced channel expression on action potential duration shortening in response to severe metabolic stress is yet to be established. Here, transgenic mice with myocardium-specific expression of a dominant negative KATP channel subunit were compared with littermate controls. Evaluation of KATP channel whole cell current and channel number/patch was assessed by patch clamp in isolated ventricular cardiomyocytes. Monophasic action potentials were monitored in retrogradely perfused, isolated hearts during the transition to hypoxic perfusate. An 80–85\% reduction in cardiac KATP channel current density results in a similar magnitude, but significantly slower rate, of shortening of the ventricular action potential duration in response to severe hypoxia, despite no significant difference in coronary flow. Therefore, the number of functional cardiac sarcolemmal KATP channels is a critical determinant of the rate of adaptation of myocardial membrane excitability, with implications for optimization of cardiac energy consumption and consequent cardioprotection under conditions of severe metabolic stress.}, number = {4}, urldate = {2017-02-27}, journal = {Biochemical and Biophysical Research Communications}, author = {Zhu, Zhiyong and Burnett, Colin M-L. and Maksymov, Gennadiy and Stepniak, Elizabeth and Sierra, Ana and Subbotina, Ekaterina and Anderson, Mark E. and Coetzee, William A. and Hodgson-Zingman, Denice M. and Zingman, Leonid V.}, month = dec, year = {2011}, keywords = {ATP-sensitive potassium channel, Glyburide, Heart, KATP, Monophasic action potential}, pages = {637--641}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7NHD3HQ3\\S0006291X11019590.html:text/html;Zhu et al (2011) - Reduction in number of sarcolemmal KATP channels slows cardiac action potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2SHWV54H\\Zhu et al (2011) - Reduction in number of sarcolemmal KATP channels slows cardiac action potential.pdf:application/pdf} } @article{shaw_electrophysiologic_1997, title = {Electrophysiologic effects of acute myocardial ischemia: a theoretical study of altered cell excitability and action potential duration}, volume = {35}, issn = {0008-6363}, shorttitle = {Electrophysiologic effects of acute myocardial ischemia}, url = {https://academic-oup-com.ezp.lib.unimelb.edu.au/cardiovascres/article/35/2/256/460403/Electrophysiologic-effects-of-acute-myocardial}, doi = {10.1016/S0008-6363(97)00093-X}, number = {2}, urldate = {2017-02-27}, journal = {Cardiovascular Research}, author = {Shaw, Robin M. and Rudy, Yoram}, month = aug, year = {1997}, pages = {256--272}, file = {Shaw_Rudy (1997) - Electrophysiologic effects of acute myocardial ischemia.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\37674B8T\\Shaw_Rudy (1997) - Electrophysiologic effects of acute myocardial ischemia.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JDXISAEJ\\Electrophysiologic-effects-of-acute-myocardial.html:text/html} } @article{bassingthwaighte_strategies_2000, title = {Strategies for the {Physiome} {Project}}, volume = {28}, issn = {0090-6964, 1573-9686}, url = {https://link-springer-com.ezp.lib.unimelb.edu.au/article/10.1114/1.1313771}, doi = {10.1114/1.1313771}, abstract = {The physiome is the quantitative description of the functioning organism in normal and pathophysiological states. The human physiome can be regarded as the virtual human. It is built upon the morphome}, language = {en}, number = {8}, urldate = {2017-02-27}, journal = {Annals of Biomedical Engineering}, author = {Bassingthwaighte, James B.}, month = aug, year = {2000}, pages = {1043--1058}, file = {Bassingthwaighte (2000) - Strategies for the Physiome Project.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SEJMWWXJ\\Bassingthwaighte (2000) - Strategies for the Physiome Project.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\92HPS3JM\\1.html:text/html} } @article{hoffman_physiological_1964, series = {Symposium on {Cardiac} {Arrhythmias}}, title = {The physiological basis of cardiac arrhythmias}, volume = {37}, issn = {0002-9343}, url = {http://www.sciencedirect.com/science/article/pii/0002934364900178}, doi = {10.1016/0002-9343(64)90017-8}, number = {5}, urldate = {2017-02-27}, journal = {The American Journal of Medicine}, author = {Hoffman, Brian F. and Cranefield, Paul F.}, month = nov, year = {1964}, pages = {670--684}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\K493VS5E\\0002934364900178.html:text/html} } @article{carmeliet_cardiac_1978, title = {Cardiac transmembrane potentials and metabolism.}, volume = {42}, copyright = {Copyright © 1978 by American Heart Association}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/42/5/577}, doi = {10.1161/01.RES.42.5.577}, language = {en}, number = {5}, urldate = {2017-02-27}, journal = {Circulation Research}, author = {Carmeliet, E.}, month = may, year = {1978}, pmid = {346251}, pages = {577--587}, file = {Carmeliet (1978) - Cardiac transmembrane potentials and metabolism.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\72Z4MFBG\\Carmeliet (1978) - Cardiac transmembrane potentials and metabolism.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8ZVZHU8I\\577.html:text/html} } @article{sperelakis_metabolic_1976, title = {A metabolic control mechanism for calcium ion influx that may protect the ventricular myocardial cell}, volume = {37}, issn = {0002-9149}, url = {http://www.sciencedirect.com/science/article/pii/0002914976904288}, doi = {10.1016/0002-9149(76)90428-8}, abstract = {Calcium ion influx into the myocardial cell during the action potential initiates and controls the degree of contraction. The Ca++ influx leads to an increase of the myoplasmic free Ca++ concentration to about 10−5 molar for activation of the myofibrils; Ca++ may also be released from the sarcoplasmic reticulum by the entering Ca++ or by voltage change across its membrane. The inward Ca++ current during the action potential plateau traverses the sarcolemma through a separate set of slow cation channels that have some peculiar properties compared to fast sodium ion channels: Slow channels are not sensitive to tetrodotoxin, have lower activation and inactivation potentials and are kinetically slow (slow activation, inactivation and recovery processes). Slow Ca++ channels require metabolic energy and are blocked by verapamil, manganese ion, lanthanum ion and acidosis. When the fast Na++ channels are blocked by tetrodotoxin or voltage inactivated by 27 millimolar potassium ion, excitability is lost but can be restored by catecholamines and methylxanthines: Propagating slowly rising electrical responses (accompanied by contractions) occur that resemble the plateau of the normal action potential. Positive inotropic agents such as norepinephrine, theophylline and histamine appear to act by elevating cyclic adenosine monophosphate (AMP) levels and increasing the number of Ca++ channels available for voltage activation. Increased cyclic AMP could lead to phosphorylation of a membrane protein constituent of the slow channels by means of a cyclic AMP-dependent protein kinase and adenosine triphosphate (ATP). Thus, the myocardial cell exercises control over the number of available slow channels and, hence, the Ca++ influx per impulse. This control mechanism could serve to protect the myocardial cell during periods of regional ischemia by acting to conserve ATP through reduced Ca++ influx and contraction, and thus preventing the affected cells from working themselves to death. The Ca++ channels in ischemic cells could be made inoperative by decreased ATP, decreased pH or accumulation of some other metabolite.}, number = {7}, urldate = {2017-02-27}, journal = {The American Journal of Cardiology}, author = {Sperelakis, Nick and Schneider, Joel A.}, month = jun, year = {1976}, pages = {1079--1085}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KA58EGRS\\0002914976904288.html:text/html} } @book{sterling_principles_2015, title = {Principles of {Neural} {Design}}, isbn = {978-0-262-02870-7}, url = {http://www.jstor.org.ezp.lib.unimelb.edu.au/stable/j.ctt17kk982}, abstract = {Neuroscience research has exploded, with more than fifty thousand neuroscientists applying increasingly advanced methods. A mountain of new facts and mechanisms has emerged. And yet a principled framework to organize this knowledge has been missing. In this book, Peter Sterling and Simon Laughlin, two leading neuroscientists, strive to fill this gap, outlining a set of organizing principles to explain the whys of neural design that allow the brain to compute so efficiently. Setting out to "reverse engineer" the brain -- disassembling it to understand it -- Sterling and Laughlin first consider why an animal should need a brain, tracing computational abilities from bacterium to protozoan to worm. They examine bigger brains and the advantages of "anticipatory regulation"; identify constraints on neural design and the need to "nanofy"; and demonstrate the routes to efficiency in an integrated molecular system, phototransduction. They show that the principles of neural design at finer scales and lower levels apply at larger scales and higher levels; describe neural wiring efficiency; and discuss learning as a principle of biological design that includes "save only what is needed."Sterling and Laughlin avoid speculation about how the brain \textit{might} work and endeavor to make sense of what is already known. Their distinctive contribution is to gather a coherent set of basic rules and exemplify them across spatial and functional scales.}, urldate = {2017-02-28}, publisher = {MIT Press}, author = {Sterling, Peter and Laughlin, Simon}, year = {2015} } @article{noauthor_cardiac_2002, title = {Cardiac {Ion} {Channels}}, volume = {64}, url = {http://dx.doi.org/10.1146/annurev.physiol.64.083101.145105}, doi = {10.1146/annurev.physiol.64.083101.145105}, abstract = {The normal electrophysiologic behavior of the heart is determined by ordered propagation of excitatory stimuli that result in rapid depolarization and slow repolarization, thereby generating action potentials in individual myocytes. Abnormalities of impulse generation, propagation, or the duration and configuration of individual cardiac action potentials form the basis of disorders of cardiac rhythm, a continuing major public health problem for which available drugs are incompletetly effective and often dangerous. The integrated activity of specific ionic currents generates action potentials, and the genes whose expression results in the molecular components underlying individual ion currents in heart have been cloned. This review discusses these new tools and how their application to the problem of arrhythmias is generating new mechanistic insights to identify patients at risk for this condition and developing improved antiarrhythmic therapies.}, number = {1}, urldate = {2017-02-28}, journal = {Annual Review of Physiology}, year = {2002}, pmid = {11826275}, pages = {431--475} } @article{linz_control_1998, title = {Control of {L}-type calcium current during the action potential of guinea-pig ventricular myocytes}, volume = {513}, issn = {0022-3751}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2231304/}, doi = {10.1111/j.1469-7793.1998.425bb.x}, abstract = {During an action potential the L-type Ca2+ current (ICa,L) activates rapidly, then partially declines leading to a sustained inward current during the plateau phase. The reason for the sustained part of ICa,L has been investigated here.In the present study the mechanisms controlling the ICa,L during an action potential were investigated quantitatively in isolated guinea-pig ventricular myocytes by whole-cell patch clamp. To measure the actual time courses of ICa,L and the corresponding L-type channel inactivation (fAP) during an action potential, action potential-clamp protocols combined with square pulses were applied.Within the first 10 ms of the action potential the ICa,L rapidly inactivated by about 50 \%; during the plateau phase inactivation proceeded to 95 \%. Later, during repolarization, the L-type channels recovered up to 25 \%.The voltage-dependent component of inactivation during an action potential was determined from measurements of L-type current carried by monovalent cations. This component of inactivation proceeded rather slowly and contributed only a little to fAP. ICa,L during an action potential is thus mainly controlled by Ca2+-dependent inactivation.In order to investigate the source of the Ca2+ controlling fAP, internal Ca2+ homeostasis was manipulated by the use of Ca2+ buffers (EGTA, BAPTA), by blocking Na+−Ca2+ exchange, or by blocking Ca2+ release from the sarcoplasmic reticulum (SR). Internal BAPTA markedly reduced the L-type channel inactivation during the entire action potential, whereas EGTA affected fAP only during the middle and late plateau phases. Inhibition of Na+−Ca2+ exchange markedly increased inactivation of L-type channels. Although blocking SR Ca2+ release decreased the fura-2-measured cytoplasmic Ca2+ concentration ([Ca2+]i) transient by about 90 \%, it reduced L-type channel inactivation only during the initial 50 ms of the action potential. Thus, it is Ca2+ entering the cell through the L-type channels that controls the inactivation process for the majority of the action potential. Nevertheless, SR Ca2+-release contributes 40–50 \% to L-type channel inactivation during the initial period of the action potential. However, the maximum extent of inactivation reached during the plateau is independent of Ca2+ released from the SR.For the first time, the actual time course of L-type channel inactivation has been directly determined during an action potential under various defined [Ca2+]i conditions. Thereby, the relative contribution to ICa,L inactivation of voltage, Ca2+ entering through L-type channels, and Ca2+ being released from the SR could be directly demonstrated.}, number = {Pt 2}, urldate = {2017-02-28}, journal = {The Journal of Physiology}, author = {Linz, Klaus W and Meyer, Rainer}, month = dec, year = {1998}, pmid = {9806993}, pmcid = {PMC2231304}, pages = {425--442} } @article{shibasaki_conductance_1987, title = {Conductance and kinetics of delayed rectifier potassium channels in nodal cells of the rabbit heart.}, volume = {387}, url = {https://www-ncbi-nlm-nih-gov.ezp.lib.unimelb.edu.au/pmc/articles/PMC1192502/}, abstract = {1. The delayed rectifier K+ current (IK) of single pace-maker cells from the sino-atrial node and the atrioventricular node of the rabbit heart was investigated using the whole-cell and cell-attached configurations of the patch-clamp technique. 2. The ...}, language = {en}, urldate = {2017-03-01}, journal = {The Journal of Physiology}, author = {Shibasaki, T.}, month = jun, year = {1987}, pmid = {2443680}, pages = {227}, file = {Shibasaki (1987) - Conductance and kinetics of delayed rectifier potassium channels in nodal cells.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KBVP6URK\\Shibasaki (1987) - Conductance and kinetics of delayed rectifier potassium channels in nodal cells.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FEVJ4QR5\\PMC1192502.html:text/html} } @article{silva_subunit_2005, title = {Subunit interaction determines {IKs} participation in cardiac repolarization and repolarization reserve}, volume = {112}, issn = {1524-4539}, doi = {10.1161/CIRCULATIONAHA.105.543306}, abstract = {BACKGROUND: The role of IKs, the slow delayed rectifier K+ current, in cardiac ventricular repolarization has been a subject of debate. METHODS AND RESULTS: We develop a detailed Markov model of IKs and its alpha-subunit KCNQ1 and examine their kinetic properties during the cardiac ventricular action potential at different rates. We observe that interaction between KCNQ1 and KCNE1 (the beta-subunit) confers kinetic properties on IKs that make it suitable for participation in action potential repolarization and its adaptation to rate changes; in particular, the channel develops an available reserve of closed states near the open state that can open rapidly on demand. CONCLUSIONS: Because of its ability to form an available reserve, IKs can function as a repolarization reserve when IKr, the rapid delayed rectifier, is reduced by disease or drug and can prevent excessive action potential prolongation and development of arrhythmogenic early afterdepolarizations.}, language = {eng}, number = {10}, journal = {Circulation}, author = {Silva, Jonathan and Rudy, Yoram}, month = sep, year = {2005}, pmid = {16129795}, pmcid = {PMC1820744}, keywords = {Action Potentials, Animals, Anura, Computer simulation, Guinea Pigs, Humans, Ion Channel Gating, KCNQ1 Potassium Channel, kinetics, Long QT Syndrome, Markov Chains, Models, Biological, Myocardial Contraction, Oocytes, Potassium Channels, Voltage-Gated, Protein Subunits, Reproducibility of Results}, pages = {1384--1391} } @article{mcallister_reconstruction_1975, title = {Reconstruction of the electrical activity of cardiac {Purkinje} fibres.}, volume = {251}, url = {https://www-ncbi-nlm-nih-gov.ezp.lib.unimelb.edu.au/pmc/articles/PMC1348375/}, abstract = {1. The electrical activity of Cardiac Purkinje fibres was reconstructed using a mathematical model of the membrane current. The individual components of ionic curent were described by equations which wee based as closely as possible on previous experiments ...}, language = {en}, number = {1}, urldate = {2017-03-02}, journal = {The Journal of Physiology}, author = {McAllister, R. E. and Noble, D. and Tsien, R. W.}, month = sep, year = {1975}, pmid = {1185607}, pages = {1}, file = {McAllister et al (1975) - Reconstruction of the electrical activity of cardiac Purkinje fibres.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9JEEBW6E\\McAllister et al (1975) - Reconstruction of the electrical activity of cardiac Purkinje fibres.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8MSEJMTD\\PMC1348375.html:text/html} } @article{kurachi_voltage-dependent_1985, title = {Voltage-dependent activation of the inward-rectifier potassium channel in the ventricular cell membrane of guinea-pig heart.}, volume = {366}, url = {https://www-ncbi-nlm-nih-gov.ezp.lib.unimelb.edu.au/pmc/articles/PMC1193038/}, abstract = {The activation kinetics of the inward-rectifier K+ channel were studied by single-channel recording in isolated single cells of the guinea-pig ventricle with two different extracellular concentrations of K+ ([K+]o 150 and 75 mM). When voltage pulses were ...}, language = {en}, urldate = {2017-03-02}, journal = {The Journal of Physiology}, author = {Kurachi, Y.}, month = sep, year = {1985}, pmid = {2414434}, pages = {365}, file = {Kurachi (1985) - Voltage-dependent activation of the inward-rectifier potassium channel in the.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UMWVDFUK\\Kurachi (1985) - Voltage-dependent activation of the inward-rectifier potassium channel in the.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZCAR3CZX\\PMC1193038.html:text/html} } @article{winslow_modeling_2016, title = {Modeling calcium regulation of contraction, energetics, signaling, and transcription in the cardiac myocyte}, volume = {8}, issn = {1939-005X}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1002/wsbm.1322/abstract}, doi = {10.1002/wsbm.1322}, abstract = {Calcium (Ca2+) plays many important regulatory roles in cardiac muscle cells. In the initial phase of the action potential, influx of Ca2+ through sarcolemmal voltage-gated L-type Ca2+ channels (LCCs) acts as a feed-forward signal that triggers a large release of Ca2+ from the junctional sarcoplasmic reticulum (SR). This Ca2+ drives heart muscle contraction and pumping of blood in a process known as excitation–contraction coupling (ECC). Triggered and released Ca2+ also feed back to inactivate LCCs, attenuating the triggered Ca2+ signal once release has been achieved. The process of ECC consumes large amounts of ATP. It is now clear that in a process known as excitation–energetics coupling, Ca2+ signals exert beat-to-beat regulation of mitochondrial ATP production that closely couples energy production with demand. This occurs through transport of Ca2+ into mitochondria, where it regulates enzymes of the tricarboxylic acid cycle. In excitation–signaling coupling, Ca2+ activates a number of signaling pathways in a feed-forward manner. Through effects on their target proteins, these interconnected pathways regulate Ca2+ signals in complex ways to control electrical excitability and contractility of heart muscle. In a process known as excitation–transcription coupling, Ca2+ acting primarily through signal transduction pathways also regulates the process of gene transcription. Because of these diverse and complex roles, experimentally based mechanistic computational models are proving to be very useful for understanding Ca2+ signaling in the cardiac myocyte. WIREs Syst Biol Med 2016, 8:37–67. doi: 10.1002/wsbm.1322 For further resources related to this article, please visit the WIREs website.}, language = {en}, number = {1}, urldate = {2017-03-06}, journal = {Wiley Interdisciplinary Reviews: Systems Biology and Medicine}, author = {Winslow, Raimond L. and Walker, Mark A. and Greenstein, Joseph L.}, month = jan, year = {2016}, pages = {37--67} } @article{li_inhibiting_2014, title = {Inhibiting {Na}+/{K}+ {ATPase} {Can} {Impair} {Mitochondrial} {Energetics} and {Induce} {Abnormal} {Ca}2+ {Cycling} and {Automaticity} in {Guinea} {Pig} {Cardiomyocytes}}, volume = {9}, issn = {1932-6203}, url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0093928}, doi = {10.1371/journal.pone.0093928}, abstract = {Cardiac glycosides have been used for the treatment of heart failure because of their capabilities of inhibiting Na+/K+ ATPase (NKA), which raises [Na+]i and attenuates Ca2+ extrusion via the Na+/Ca2+ exchanger (NCX), causing [Ca2+]i elevation. The resulting [Ca2+]i accumulation further enhances Ca2+-induced Ca2+ release, generating the positive inotropic effect. However, cardiac glycosides have some toxic and side effects such as arrhythmogenesis, confining their extensive clinical applications. The mechanisms underlying the proarrhythmic effect of glycosides are not fully understood. Here we investigated the mechanisms by which glycosides could cause cardiac arrhythmias via impairing mitochondrial energetics using an integrative computational cardiomyocyte model. In the simulations, the effect of glycosides was mimicked by blocking NKA activity. Results showed that inhibiting NKA not only impaired mitochondrial Ca2+ retention (thus suppressed reactive oxygen species (ROS) scavenging) but also enhanced oxidative phosphorylation (thus increased ROS production) during the transition of increasing workload, causing oxidative stress. Moreover, concurrent blocking of mitochondrial Na+/Ca2+ exchanger, but not enhancing of Ca2+ uniporter, alleviated the adverse effects of NKA inhibition. Intriguingly, NKA inhibition elicited Ca2+ transient and action potential alternans under more stressed conditions such as severe ATP depletion, augmenting its proarrhythmic effect. This computational study provides new insights into the mechanisms underlying cardiac glycoside-induced arrhythmogenesis. The findings suggest that targeting both ion handling and mitochondria could be a very promising strategy to develop new glycoside-based therapies in the treatment of heart failure.}, number = {4}, urldate = {2017-03-06}, journal = {PLOS ONE}, author = {Li, Qince and Pogwizd, Steven M. and Prabhu, Sumanth D. and Zhou, Lufang}, month = apr, year = {2014}, keywords = {Action Potentials, arrhythmia, Cardiac pacing, Cytosol, Glycosides, mitochondria, Mitochondrial membrane, Oxidative stress}, pages = {e93928}, file = {Li et al (2014) - Inhibiting Na+-K+ ATPase Can Impair Mitochondrial Energetics and Induce.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SKJUTW2N\\Li et al (2014) - Inhibiting Na+-K+ ATPase Can Impair Mitochondrial Energetics and Induce.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JKX543EX\\article.html:text/html} } @incollection{stemmler_energetically_2011, title = {Energetically {Optimal} {Action} {Potentials}}, url = {http://papers.nips.cc/paper/4327-energetically-optimal-action-potentials.pdf}, urldate = {2017-03-06}, booktitle = {Advances in {Neural} {Information} {Processing} {Systems} 24}, publisher = {Curran Associates, Inc.}, author = {Stemmler, Martin B. and Sengupta, Biswa and Laughlin, Simon and Niven, Jeremy}, editor = {Shawe-Taylor, J. and Zemel, R. S. and Bartlett, P. L. and Pereira, F. and Weinberger, K. Q.}, year = {2011}, pages = {1566--1574}, file = {NIPS Snapshort:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KRITQ7SP\\4327-energetically-optimal-action-potentials.html:text/html;Stemmler et al (2011) - Energetically Optimal Action Potentials.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BPQH29HH\\Stemmler et al (2011) - Energetically Optimal Action Potentials.pdf:application/pdf} } @book{paynter_analysis_1961, title = {Analysis and design of engineering systems}, publisher = {MIT press}, author = {Paynter, Henry M.}, year = {1961} } @book{dayan_theoretical_2001, title = {Theoretical neuroscience}, volume = {806}, url = {http://inis.jinr.ru/sl/Cs_Computer%20science/CsGn_Genetic,%20neural/Dayan%20P.,%20Abbott%20L.F.%20Theoretical%20neuroscience%20(2002)(432s).pdf.gz}, urldate = {2017-03-08}, publisher = {Cambridge, MA: MIT Press}, author = {Dayan, Peter and Abbott, Laurence F.}, year = {2001} } @article{wellstead_rocontrol_2008, title = {The rôle of control and system theory in systems biology}, volume = {32}, issn = {1367-5788}, url = {http://www.sciencedirect.com/science/article/pii/S1367578808000047}, doi = {10.1016/j.arcontrol.2008.02.001}, abstract = {The use of new technology and mathematics to study the systems of nature is one of the most significant scientific trends of the century. Driven by the need for more precise scientific understanding, advances in automated measurement are providing rich new sources of biological and physiological data. These data provide information to create mathematical models of increasing sophistication and realism—models that can emulate biological and physiological systems with sufficient accuracy to advance our understanding of living systems and disease mechanisms. New measurement and modelling methods set the stage for control and systems theory to play their rôle in seeking out the mechanisms and principles that regulate life. It is of inestimable importance for the future of control as a discipline that this rôle is performed in the correct manner. If we handle the area wisely then living systems will present a seemingly boundless range of important new problems—just as physical and engineering systems have done in previous centuries. But there is a crucial difficulty. Faced with a bewildering array of choices in an unfamiliar area, how does a researcher select a worthwhile and fruitful problem? This article is an attempt to help by offering a control-oriented guide to the labyrinthine world of biology/physiology and its control research opportunities.}, number = {1}, urldate = {2017-03-08}, journal = {Annual Reviews in Control}, author = {Wellstead, Peter and Bullinger, Eric and Kalamatianos, Dimitrios and Mason, Oliver and Verwoerd, Mark}, month = apr, year = {2008}, keywords = {Biology, Computational physiology, Control systems, Estimation, Mathematical biology, System identification, Systems Biology, Systems dynamics}, pages = {33--47} } @article{alekseev_sarcolemmal_2010, title = {Sarcolemmal {ATP}-{Sensitive} {K}+ {Channels} {Control} {Energy} {Expenditure} {Determining} {Body} {Weight}}, volume = {11}, issn = {1550-4131}, url = {http://www.sciencedirect.com/science/article/pii/S1550413109003738}, doi = {10.1016/j.cmet.2009.11.009}, abstract = {Summary Metabolic processes that regulate muscle energy use are major determinants of bodily energy balance. Here, we find that sarcolemmal ATP-sensitive K+ (KATP) channels, which couple membrane excitability with cellular metabolic pathways, set muscle energy expenditure under physiological stimuli. Disruption of KATP channel function provoked, under conditions of unaltered locomotor activity and blood substrate availability, an extra energy cost of cardiac and skeletal muscle performance. Inefficient fuel metabolism in KATP channel-deficient striated muscles reduced glycogen and fat body depots, promoting a lean phenotype. The propensity to lesser body weight imposed by KATP channel deficit persisted under a high-fat diet, yet obesity restriction was achieved at the cost of compromised physical endurance. Thus, sarcolemmal KATP channels govern muscle energy economy, and their downregulation in a tissue-specific manner could present an antiobesity strategy by rendering muscle increasingly thermogenic at rest and less fuel efficient during exercise.}, number = {1}, urldate = {2017-03-08}, journal = {Cell Metabolism}, author = {Alekseev, Alexey E. and Reyes, Santiago and Yamada, Satsuki and Hodgson-Zingman, Denice M. and Sattiraju, Srinivasan and Zhu, Zhiyong and Sierra, Ana and Gerbin, Marina and Coetzee, William A. and Goldhamer, David J. and Terzic, Andre and Zingman, Leonid V.}, month = jan, year = {2010}, keywords = {HUMDISEASE}, pages = {58--69} } @article{zingman_exercise-induced_2011, title = {Exercise-induced expression of cardiac {ATP}-sensitive potassium channels promotes action potential shortening and energy conservation}, volume = {51}, issn = {0022-2828}, url = {http://www.sciencedirect.com/science/article/pii/S0022282811001222}, doi = {10.1016/j.yjmcc.2011.03.010}, abstract = {Physical activity is one of the most important determinants of cardiac function. The ability of the heart to increase delivery of oxygen and metabolic fuels relies on an array of adaptive responses necessary to match bodily demand while avoiding exhaustion of cardiac resources. The ATP-sensitive potassium (KATP) channel has the unique ability to adjust cardiac membrane excitability in accordance with ATP and ADP levels, and up-regulation of its expression that occurs in response to exercise could represent a critical element of this adaption. However, the mechanism by which KATP channel expression changes result in a beneficial effect on cardiac excitability and function remains to be established. Here, we demonstrate that an exercise-induced rise in KATP channel expression enhanced the rate and magnitude of action potential shortening in response to heart rate acceleration. This adaptation in membrane excitability promoted significant reduction in cardiac energy consumption under escalating workloads. Genetic disruption of normal KATP channel pore function abolished the exercise-related changes in action potential duration adjustment and caused increased cardiac energy consumption. Thus, an expression-driven enhancement in the KATP channel-dependent membrane response to alterations in cardiac workload represents a previously unrecognized mechanism for adaptation to physical activity and a potential target for cardioprotection.}, number = {1}, urldate = {2017-03-08}, journal = {Journal of Molecular and Cellular Cardiology}, author = {Zingman, Leonid V. and Zhu, Zhiyong and Sierra, Ana and Stepniak, Elizabeth and Burnett, Colin M. -L. and Maksymov, Gennadiy and Anderson, Mark E. and Coetzee, William A. and Hodgson-Zingman, Denice M.}, month = jul, year = {2011}, keywords = {Exercise, Heart rate, KATP, K-ATP, Oxygen consumption, Remodeling}, pages = {72--81} } @article{sengupta_action_2010, title = {Action {Potential} {Energy} {Efficiency} {Varies} {Among} {Neuron} {Types} in {Vertebrates} and {Invertebrates}}, volume = {6}, issn = {1553-7358}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1000840}, doi = {10.1371/journal.pcbi.1000840}, abstract = {Author Summary Neurons produce a myriad of action potentials with different shapes and varying heights and widths; underlying these action potentials are highly nonlinear, voltage-dependent ionic conductances with varying biophysical properties. Each action potential comes at a cost: the brain uses a substantial portion of its total energy budget to generate and propagate action potentials. Recent results show that some mammalian action potentials have biophysical properties that make them energy efficient. Yet, how widespread are energy efficient action potentials? Using mathematical analysis and modeling, we show that there is no direct relationship between the height, width, and the energy consumption of a single action potential. Furthermore, we establish that many mammalian action potentials have biophysical properties that reduce the overlap between their inward and outward currents so as to minimize energy consumption. This reduction in overlap results from a combination of ion channel properties uniquely tailored for each particular neuron type and the functional purpose of the action potential in that neuron. By comparing the measured biophysical parameters to the parameters produced by numerical optimization for maximal energy-efficiency, we argue that natural selection for energy-efficiency could help explain both the shape of the action potential and the underlying biophysics of ionic currents.}, number = {7}, urldate = {2017-03-08}, journal = {PLOS Computational Biology}, author = {Sengupta, Biswa and Stemmler, Martin and Laughlin, Simon B. and Niven, Jeremy E.}, month = jul, year = {2010}, keywords = {Action Potentials, Axons, Interneurons, Motor neurons, Neurons, optimization, Squids, Voltage-gated ion channels}, pages = {e1000840}, file = {pcbi.1000840.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WCGIE2P7\\pcbi.1000840.pdf:application/pdf} } @article{erecinska_relationships_1990, title = {Relationships between the neuronal sodium/potassium pump and energy metabolism. {Effects} of {K}+, {Na}+, and adenosine triphosphate in isolated brain synaptosomes.}, volume = {95}, copyright = {© 1990 Rockefeller University Press}, issn = {0022-1295, 1540-7748}, url = {http://jgp.rupress.org.ezp.lib.unimelb.edu.au/content/95/4/591}, doi = {10.1085/jgp.95.4.591}, abstract = {The relationships between Na/K pump activity and adenosine triphosphate (ATP) production were determined in isolated rat brain synaptosomes. The activity of the enzyme was modulated by altering [K+]e, [Na+]i, and [ATP]i while synaptosomal oxygen uptake and lactate production were measured simultaneously. KCl increased respiration and glycolysis with an apparent Km of about 1 mM which suggests that, at the [K+]e normally present in brain, 3.3-4 mM, the pump is near saturation with this cation. Depolarization with 6-40 mM KCl had negligible effect on ouabain-sensitive O2 uptake indicating that at the voltages involved the activity of the Na/K ATPase is largely independent of membrane potential. Increases in [Na+]i by addition of veratridine markedly enhanced glycoside-inhibitable respiration and lactate production. Calculations of the rates of ATP synthesis necessary to support the operation of the pump showed that greater than 90\% of the energy was derived from oxidative phosphorylation. Consistent with this: (a) the ouabain-sensitive Rb/O2 ratio was close to 12 (i.e., Rb/ATP ratio of 2); (b) inhibition of mitochondrial ATP synthesis by Amytal resulted in a decrease in the glycoside-dependent rate of 86Rb uptake. Analyses of the mechanisms responsible for activation of the energy-producing pathways during enhanced Na and K movements indicate that glycolysis is predominantly stimulated by increase in activity of phosphofructokinase mediated via a rise in the concentrations of adenosine monophosphate [AMP] and inorganic phosphate [Pi] and a fall in the concentration of phosphocreatine [PCr]; the main moving force for the elevation in mitochondrial ATP generation is the decline in [ATP]/[ADP] [Pi] (or equivalent) and consequent readjustments in the ratio of the intramitochondrial pyridine nucleotides [( NAD]m/[NADH]m). Direct stimulation of pyruvate dehydrogenase by calcium appears to be of secondary importance. It is concluded that synaptosomal Na/K pump is fueled primarily by oxidative phosphorylation and that a fall in [ATP]/[ADP][Pi] is the chief factor responsible for increased energy production.}, language = {en}, number = {4}, urldate = {2017-03-08}, journal = {The Journal of General Physiology}, author = {Erecińska, M. and Dagani, F.}, month = apr, year = {1990}, pmid = {2159972}, pages = {591--616} } @article{rasmusson_mathematical_1990, title = {A mathematical model of electrophysiological activity in a bullfrog atrial cell}, volume = {259}, copyright = {Copyright © 1990 the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/259/2/h370}, abstract = {We have developed a model of cardiac atrial electrical activity based on voltage-clamp measurements obtained from single cells isolated from the bullfrog atrium. These measurements have allowed us to simulate a number of processes thought to be important in action potential initiation, repolarization, and the excitation-contraction (EC) coupling process. In this atrial model, the cell membrane contains both channel-mediated (Na+, Ca2+, inward rectifier K+, delayed rectifier K+, linear background leak) and transporter-mediated (Na(+)-K+ pump, Na(+)-Ca2+ exchanger, Ca2+ pump) currents. The cell is surrounded extracellularly by a diffusion-limited space. The intracellular volume contains Ca2(+)-binding proteins (calmodulin, troponin). The model makes several important predictions. 1) Incomplete inactivation of the Ca2+ current provides an inward current the maintains the plateau of the action potential. 2) Activation of the delayed rectifier K+ current initiates repolarization. 3) Due to Ca2+ buffering by myoplasmic proteins the Na(+)-Ca2+ exchanger current is relatively small and has little influence on repolarization. 4) The Na(+)-K+ pump current does not play a major role in repolarization. 5) K+ accumulation and Ca2+ depletion may occur in the extracellular spaces. 6) Modulation of EC coupling is governed by interactions between the myoplasmic Ca2(+)-binding proteins; specifically, the inotropic "positive staircase effect" may be explained by interactions between Ca2+ and Mg2+ at a competitive binding site on troponin. When considered in conjunction with the results of our model of primary pacemaking in the sinus venosus [Rasmusson et al., Am. J. Physiol. 259 (Heart Circ. Physiol. 28): H352-H369, 1990], this atrial model shows how the presence or absence of certain transmembrane currents can change action potential characteristics and consequently alter the relative influence of the various transporter-mediated and channel-mediated currents.}, language = {en}, number = {2}, urldate = {2017-03-28}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {Rasmusson, R. L. and Clark, J. W. and Giles, W. R. and Robinson, K. and Clark, R. B. and Shibata, E. F. and Campbell, D. L.}, month = aug, year = {1990}, pmid = {2386218}, pages = {H370--H389}, file = {Rasmusson et al (1990) - A mathematical model of electrophysiological activity in a bullfrog atrial cell.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3MDV8M3H\\Rasmusson et al (1990) - A mathematical model of electrophysiological activity in a bullfrog atrial cell.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3BC96SWX\\h370.html:text/html} } @article{hill_heat_1938, title = {The {Heat} of {Shortening} and the {Dynamic} {Constants} of {Muscle}}, volume = {126}, issn = {0962-8452, 1471-2954}, url = {http://rspb.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/126/843/136}, doi = {10.1098/rspb.1938.0050}, language = {en}, number = {843}, urldate = {2017-04-21}, journal = {Proceedings of the Royal Society of London B: Biological Sciences}, author = {Hill, A. V.}, month = oct, year = {1938}, pages = {136--195}, file = {Hill - 1938 - The Heat of Shortening and the Dynamic Constants o.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DNBNP2JS\\Hill - 1938 - The Heat of Shortening and the Dynamic Constants o.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BM7RDP7K\\136.html:text/html} } @article{michailova_modeling_2005, title = {Modeling {Regulation} of {Cardiac} {KATP} and {L}-type {Ca}2+ {Currents} by {ATP}, {ADP}, and {Mg}2+}, volume = {88}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349505732835}, doi = {10.1529/biophysj.104.046284}, abstract = {Changes in cytosolic free Mg2+ and adenosine nucleotide phosphates affect cardiac excitability and contractility. To investigate how modulation by Mg2+, ATP, and ADP of KATP and L-type Ca2+ channels influences excitation-contraction coupling, we incorporated equations for intracellular ATP and MgADP regulation of the KATP current and MgATP regulation of the L-type Ca2+ current in an ionic-metabolic model of the canine ventricular myocyte. The new model: 1), quantitatively reproduces a dose-response relationship for the effects of changes in ATP on KATP current, 2), simulates effects of ADP in modulating ATP sensitivity of KATP channel, 3), predicts activation of Ca2+ current during rapid increase in MgATP, and 4), demonstrates that decreased ATP/ADP ratio with normal total Mg2+ or increased free Mg2+ with normal ATP and ADP activate KATP current, shorten action potential, and alter ionic currents and intracellular Ca2+ signals. The model predictions are in agreement with experimental data measured under normal and a variety of pathological conditions.}, number = {3}, urldate = {2017-04-26}, journal = {Biophysical Journal}, author = {Michailova, Anushka and Saucerman, Jeffrey and Ellen Belik, Mary and McCulloch, Andrew D.}, month = mar, year = {2005}, pages = {2234--2249}, file = {Michailova et al (2005) - Modeling Regulation of Cardiac KATP and L-type Ca2+ Currents by ATP, ADP, and.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4VVU7NMX\\Michailova et al (2005) - Modeling Regulation of Cardiac KATP and L-type Ca2+ Currents by ATP, ADP, and.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VHXNFNP2\\S0006349505732835.html:text/html} } @article{cardelli_morphisms_2014, title = {Morphisms of reaction networks that couple structure to function}, volume = {8}, issn = {1752-0509}, url = {http://dx.doi.org/10.1186/1752-0509-8-84}, doi = {10.1186/1752-0509-8-84}, abstract = {The mechanisms underlying complex biological systems are routinely represented as networks. Network kinetics is widely studied, and so is the connection between network structure and behavior. However, similarity of mechanism is better revealed by relationships between network structures.}, urldate = {2017-04-26}, journal = {BMC Systems Biology}, author = {Cardelli, Luca}, year = {2014}, keywords = {Biological networks, Chemical reaction networks, Influence networks, Morphisms}, pages = {84}, annote = {Pages 84 in PDF}, file = {Cardelli (2014) - Morphisms of reaction networks that couple structure to function.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DZPNK695\\Cardelli (2014) - Morphisms of reaction networks that couple structure to function.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\9C68B33R\\1752-0509-8-84.html:text/html} } @article{borutzky_advances_1995, title = {Advances in bond graph modelling: theory, software, applications}, volume = {39}, issn = {0378-4754}, shorttitle = {Advances in bond graph modelling}, url = {http://www.sciencedirect.com/science/article/pii/0378475495001066}, doi = {10.1016/0378-4754(95)00106-6}, abstract = {Bond-graph modelling has been known for more than 30 years and is recognized to an increasing extend by academia and industries all over the world. By the same time considerable progress has been made with regard to the methodology, to the development of supporting software, and to applications in various fields of engineering. The aim of this paper is to survey more recent advances in bond graph modelling, to discuss some topics of current research, and to briefly investigate emerging relationships to other disciplines.}, number = {5}, urldate = {2017-05-09}, journal = {Mathematics and Computers in Simulation}, author = {Borutzky, W. and Dauphin-Tanguy, G. and Thoma, J. U.}, month = nov, year = {1995}, pages = {465--475}, file = {Borutzky et al (1995) - Advances in bond graph modelling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8ZJM6FBK\\Borutzky et al (1995) - Advances in bond graph modelling.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MMDTKFAS\\0378475495001066.html:text/html} } @article{gawthrop_bond_2017, title = {Bond {Graph} {Modeling} of {Chemiosmotic} {Biomolecular} {Energy} {Transduction}}, volume = {16}, issn = {1536-1241}, doi = {10.1109/TNB.2017.2674683}, abstract = {Engineering systems modeling and analysis based on the bond graph approach has been applied to biomolecular systems. In this context, the notion of a Faraday-equivalent chemical potential is introduced which allows chemical potential to be expressed in an analogous manner to electrical volts thus allowing engineering intuition to be applied to biomolecular systems. Redox reactions, and their representation by half-reactions, are key components of biological systems which involve both electrical and chemical domains. A bond graph interpretation of redox reactions is given which combines bond graphs with the Faraday-equivalent chemical potential. This approach is particularly relevant when the biomolecular system implements chemoelectrical transduction – for example chemiosmosis within the key metabolic pathway of mitochondria: oxidative phosphorylation. An alternative way of implementing computational modularity using bond graphs is introduced and used to give a physically based model of the mitochondrial electron transport chain To illustrate the overall approach, this model is analyzed using the Faraday-equivalent chemical potential approach and engineering intuition is used to guide affinity equalisation: a energy based analysis of the mitochondrial electron transport chain.}, number = {3}, journal = {IEEE Transactions on NanoBioscience}, author = {Gawthrop, P. J.}, month = apr, year = {2017}, keywords = {Analytical models, Biological system modeling, Chemicals, Computational modeling, computational systems biology, Context, Electric potential, Protons, Systems Biology}, pages = {177--188}, file = {Gawthrop (2017) - Bond Graph Modeling of Chemiosmotic Biomolecular Energy Transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DEM9UP4T\\Gawthrop (2017) - Bond Graph Modeling of Chemiosmotic Biomolecular Energy Transduction.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QEKS5KGF\\7864453.html:text/html} } @article{gawthrop_bond_2016, title = {Bond {Graph} {Modelling} of {Chemiosmotic} {Biomolecular} {Energy} {Transduction}}, url = {http://arxiv.org/abs/1611.04264}, abstract = {Engineering systems modelling and analysis based on the bond graph approach has been applied to biomolecular systems. In this context, the notion of a Faraday-equivalent chemical potential is introduced which allows chemical potential to be expressed in an analogous manner to electrical volts thus allowing engineering intuition to be applied to biomolecular systems. Redox reactions, and their representation by half-reactions, are key components of biological systems which involve both electrical and chemical domains. A bond graph interpretation of redox reactions is given which combines bond graphs with the Faraday- equivalent chemical potential. This approach is particularly relevant when the biomolecular system implements chemoelectrical transduction - for example chemiosmosis within the key metabolic pathway of mitochondria: oxidative phosphorylation. An alternative way of implementing computational modularity using bond graphs is introduced and used to give a physically based model of the mitochondrial electron transport chain. To illustrate the overall approach, this model is analysed using the Faraday-equivalent chemical potential approach and engineering intuition is used to guide affinity equalisation: a energy based analysis of the mitochondrial electron transport chain.}, urldate = {2017-05-15}, journal = {arXiv:1611.04264 [q-bio]}, author = {Gawthrop, Peter}, month = nov, year = {2016}, note = {arXiv: 1611.04264}, keywords = {Quantitative Biology - Molecular Networks}, file = {arXiv.org Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JDG7KK44\\1611.html:text/html;Gawthrop (2016) - Bond Graph Modelling of Chemiosmotic Biomolecular Energy Transduction.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BPUIHJVZ\\Gawthrop (2016) - Bond Graph Modelling of Chemiosmotic Biomolecular Energy Transduction.pdf:application/pdf} } @article{doerr_ionic_1990, title = {Ionic currents contributing to the action potential in single ventricular myocytes of the guinea pig studied with action potential clamp}, volume = {416}, issn = {0031-6768, 1432-2013}, url = {https://link-springer-com.ezp.lib.unimelb.edu.au/article/10.1007/BF00392058}, doi = {10.1007/BF00392058}, abstract = {With the action potential clamp procedure we studied the contribution of various ionic currents to the action potential in single ventricular myocytes. Action potentials were elicited by a current pul}, language = {en}, number = {3}, urldate = {2017-05-18}, journal = {Pflügers Archiv}, author = {Doerr, T. and Denger, R. and Doerr, A. and Trautwein, W.}, month = may, year = {1990}, pages = {230--237}, file = {Doerr et al (1990) - Ionic currents contributing to the action potential in single ventricular.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\M57EFS3C\\Doerr et al (1990) - Ionic currents contributing to the action potential in single ventricular.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3D9GGI6W\\10.html:text/html} } @article{ten_tusscher_alternans_2006, title = {Alternans and spiral breakup in a human ventricular tissue model}, volume = {291}, copyright = {Copyright © 2006 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/291/3/H1088}, doi = {10.1152/ajpheart.00109.2006}, abstract = {Ventricular fibrillation (VF) is one of the main causes of death in the Western world. According to one hypothesis, the chaotic excitation dynamics during VF are the result of dynamical instabilities in action potential duration (APD) the occurrence of which requires that the slope of the APD restitution curve exceeds 1. Other factors such as electrotonic coupling and cardiac memory also determine whether these instabilities can develop. In this paper we study the conditions for alternans and spiral breakup in human cardiac tissue. Therefore, we develop a new version of our human ventricular cell model, which is based on recent experimental measurements of human APD restitution and includes a more extensive description of intracellular calcium dynamics. We apply this model to study the conditions for electrical instability in single cells, for reentrant waves in a ring of cells, and for reentry in two-dimensional sheets of ventricular tissue. We show that an important determinant for the onset of instability is the recovery dynamics of the fast sodium current. Slower sodium current recovery leads to longer periods of spiral wave rotation and more gradual conduction velocity restitution, both of which suppress restitution-mediated instability. As a result, maximum restitution slopes considerably exceeding 1 (up to 1.5) may be necessary for electrical instability to occur. Although slopes necessary for the onset of instabilities found in our study exceed 1, they are within the range of experimentally measured slopes. Therefore, we conclude that steep APD restitution-mediated instability is a potential mechanism for VF in the human heart.}, language = {en}, number = {3}, urldate = {2017-05-18}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {ten Tusscher, K. H. W. J. and Panfilov, A. V.}, month = sep, year = {2006}, pmid = {16565318}, pages = {H1088--H1100}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7K96HI4D\\H1088.html:text/html;Tusscher_Panfilov (2006) - Alternans and spiral breakup in a human ventricular tissue model.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S484ERQK\\Tusscher_Panfilov (2006) - Alternans and spiral breakup in a human ventricular tissue model.pdf:application/pdf} } @article{ten_tusscher_model_2004, title = {A model for human ventricular tissue}, volume = {286}, copyright = {Copyright © 2004 by the American Physiological Society}, issn = {0363-6135, 1522-1539}, url = {http://ajpheart.physiology.org.ezp.lib.unimelb.edu.au/content/286/4/H1573}, doi = {10.1152/ajpheart.00794.2003}, abstract = {The experimental and clinical possibilities for studying cardiac arrhythmias in human ventricular myocardium are very limited. Therefore, the use of alternative methods such as computer simulations is of great importance. In this article we introduce a mathematical model of the action potential of human ventricular cells that, while including a high level of electrophysiological detail, is computationally cost-effective enough to be applied in large-scale spatial simulations for the study of reentrant arrhythmias. The model is based on recent experimental data on most of the major ionic currents: the fast sodium, L-type calcium, transient outward, rapid and slow delayed rectifier, and inward rectifier currents. The model includes a basic calcium dynamics, allowing for the realistic modeling of calcium transients, calcium current inactivation, and the contraction staircase. We are able to reproduce human epicardial, endocardial, and M cell action potentials and show that differences can be explained by differences in the transient outward and slow delayed rectifier currents. Our model reproduces the experimentally observed data on action potential duration restitution, which is an important characteristic for reentrant arrhythmias. The conduction velocity restitution of our model is broader than in other models and agrees better with available data. Finally, we model the dynamics of spiral wave rotation in a two-dimensional sheet of human ventricular tissue and show that the spiral wave follows a complex meandering pattern and has a period of 265 ms. We conclude that the proposed model reproduces a variety of electrophysiological behaviors and provides a basis for studies of reentrant arrhythmias in human ventricular tissue.}, language = {en}, number = {4}, urldate = {2017-05-18}, journal = {American Journal of Physiology - Heart and Circulatory Physiology}, author = {ten Tusscher, K. H. W. J. and Noble, D. and Noble, P. J. and Panfilov, A. V.}, month = apr, year = {2004}, pmid = {14656705}, pages = {H1573--H1589}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5PSJTFFT\\H1573.html:text/html;Tusscher et al (2004) - A model for human ventricular tissue.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W56N2N7B\\Tusscher et al (2004) - A model for human ventricular tissue.pdf:application/pdf} } @article{jost_restricting_2005, title = {Restricting {Excessive} {Cardiac} {Action} {Potential} and {QT} {Prolongation}}, volume = {112}, copyright = {© 2005}, issn = {0009-7322, 1524-4539}, url = {http://circ.ahajournals.org.ezp.lib.unimelb.edu.au/content/112/10/1392}, doi = {10.1161/CIRCULATIONAHA.105.550111}, abstract = {Background— Although pharmacological block of the slow, delayed rectifier potassium current (IKs) by chromanol 293B, L-735,821, or HMR-1556 produces little effect on action potential duration (APD) in isolated rabbit and dog ventricular myocytes, the effect of IKs block on normal human ventricular muscle APD is not known. Therefore, studies were conducted to elucidate the role of IKs in normal human ventricular muscle and in preparations in which both repolarization reserve was attenuated and sympathetic activation was increased by exogenous dofetilide and adrenaline. Methods and Results— Preparations were obtained from undiseased organ donors. Action potentials were measured in ventricular trabeculae and papillary muscles using conventional microelectrode techniques; membrane currents were measured in ventricular myocytes using voltage-clamp techniques. Chromanol 293B (10 μmol/L), L-735,821 (100 nmol/L), and HMR-1556 (100 nmol/L and 1 μmol/L) produced a {\textless}12-ms change in APD while pacing at cycle lengths ranging from 300 to 5000 ms, whereas the IKr blockers sotalol and E-4031 markedly lengthened APD. In voltage-clamp experiments, L-735,821 and chromanol 293B each blocked IKs in the presence of E-4031 to block IKr. The E-4031–sensitive current (IKr) at the end of a 150-ms-long test pulse to 30 mV was 32.9±6.7 pA (n=8); the L-735,821–sensitive current (IKs) magnitude was 17.8±2.94 pA (n=10). During a longer 500-ms test pulse, IKr was not substantially changed (33.6±6.1 pA; n=8), and IKs was significantly increased (49.6±7.24 pA; n=10). On application of an “action potential–like” test pulse, IKr increased as voltage became more negative, whereas IKs remained small throughout all phases of the action potential–like test pulse. In experiments in which APD was first lengthened by 50 nmol/L dofetilide and sympathetic activation was increased by 1 μmol/L adrenaline, 1 μmol/L HMR-1556 significantly increased APD by 14.7±3.2\% (P{\textless}0.05; n=3). Conclusions— Pharmacological IKs block in the absence of sympathetic stimulation plays little role in increasing normal human ventricular muscle APD. However, when human ventricular muscle repolarization reserve is attenuated, IKs plays an increasingly important role in limiting action potential prolongation.}, language = {en}, number = {10}, urldate = {2017-05-19}, journal = {Circulation}, author = {Jost, Norbert and Virág, László and Bitay, Miklós and Takács, János and Lengyel, Csaba and Biliczki, Péter and Nagy, Zsolt and Bogáts, Gábor and Lathrop, David A. and Papp, Julius G. and Varró, András}, month = sep, year = {2005}, pmid = {16129791}, keywords = {arrhythmia, Electrophysiology, ion channels, long-QT syndrome, potassium channels}, pages = {1392--1399}, file = {Jost et al (2005) - Restricting Excessive Cardiac Action Potential and QT Prolongation.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NSB9EH4R\\Jost et al (2005) - Restricting Excessive Cardiac Action Potential and QT Prolongation.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FF7BSP5M\\1392.html:text/html} } @article{schramm_energy_1994, title = {The energy expenditure of actomyosin-{ATPase}, {Ca}(2+)-{ATPase} and {Na}+,{K}(+)-{ATPase} in guinea-pig cardiac ventricular muscle.}, volume = {481}, issn = {0022-3751}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1155908/}, abstract = {1. The rate of heat production (heat rate) and isometric twitch tension of ventricular trabeculae isolated from guinea-pig heart were measured at 37 degrees C in order to determine the relative contributions of actomyosin-ATPase, Ca(2+)-ATPase and Na+,K(+)-ATPase to myocardial energy metabolism. 2. The increase in heat rate recorded during isometric contractions at optimal length (contraction-related heat production) was 19.1 +/- 1.2 mW cm-3 at a stimulation rate of 2 Hz. The tension-time integral of individual contractions measured under the same conditions was 147 +/- 15 mM s cm-2. 3. The heat production of the actomyosin-ATPase was determined by inhibiting the contractile proteins with 2,3-butanedione monoxime (BDM). Contraction-related heat production was reduced by 0.219 +/- 0.010 and the isometric tension-time integral was reduced by 0.288 +/- 0.016 in the presence of 1 mM BDM. From these data an estimate of 0.76 for the relative contribution of the actomyosin-ATPase to contraction-related heat production was derived. 4. The heat production related to actomyosin-ATPase plus Ca(2+)-ATPase was studied by blocking Ca2+ influx into the myocardial cells with a solution containing 100 microM Ca2+ and 400 microM Ni2+. In this solution contraction-related heat production was reduced by 0.907 +/- 0.012. Comparison of this value with the component attributable to the actomyosin-ATPase yields an estimate of 0.15 for the relative contribution of the Ca(2+)-ATPase to contraction related heat production. 5. The heat production related to the Na+,K(+)-ATPase in resting preparations was studied by blocking the sodium pump with 400 microM dihydro-ouabain (DHO). DHO produced a transient decrease in heat rate lasting 1-2 min, which was followed by a secondary increase. From the heat transient produced by DHO the heat rate related to the Na+,K(+)-ATPase in the steady state was extrapolated. The relative contribution of the sodium pump to resting heat production was estimated to be 0.17. 6. The heat production related to the Na+,K(+)-ATPase in contracting preparations was studied by first blocking Ca2+ influx with 100 microM Ca2+ and 400 microM Ni2+, and then inhibiting the sodium pump with 400 microM dihydro-ouabain (DHO). The relative contribution of the sodium pump to contraction-related heat production extrapolated from these data was 0.10, which agreed well with the fraction of contraction-related heat production persisting after blockage of actomyosin-ATPase and Ca(2+)-ATPase (0.09).(ABSTRACT TRUNCATED AT 400 WORDS)}, number = {Pt 3}, urldate = {2017-05-23}, journal = {The Journal of Physiology}, author = {Schramm, M and Klieber, H G and Daut, J}, month = dec, year = {1994}, pmid = {7707233}, pmcid = {PMC1155908}, pages = {647--662}, file = {Schramm et al (1994) - The energy expenditure of actomyosin-ATPase, Ca(2+)-ATPase and Na+,K(+)-ATPase.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\H4KV446Q\\Schramm et al (1994) - The energy expenditure of actomyosin-ATPase, Ca(2+)-ATPase and Na+,K(+)-ATPase.pdf:application/pdf} } @incollection{destexhe_thermodynamic_2014, title = {Thermodynamic {Models} of {Ion} {Channels}}, copyright = {©2014 Springer Science+Business Media New York}, isbn = {978-1-4614-7320-6}, url = {http://link.springer.com/referenceworkentry/10.1007/978-1-4614-7320-6_136-1}, abstract = {DefinitionThermodynamic models provide a kinetic description of ion channels starting from first principles. Instead of using empirical functions for the voltage dependence of the parameters of the ion channel, they are deduced from a physically plausible framework. This framework formalizes the effect of the interaction between the electric field and the ion channel. This interaction can be linear or nonlinear, leading to different classes of models for voltage-dependent ion channels.Detailed DescriptionIntroductionThe first quantitative description of the voltage dependence of ionic currents and their role in generating action potentials was provided by Hodgkin and Huxley (1952). This description, however, was semiempirical. They postulated that the ionic conductance was dependent on the assembly of “gating particles,” acting independently and in a voltage-dependent manner. This formalism gave rise to the well-known Hodgkin-Huxley set of equations, which could account quantitatively ...}, language = {en}, urldate = {2017-05-23}, booktitle = {Encyclopedia of {Computational} {Neuroscience}}, publisher = {Springer New York}, author = {Destexhe, Prof Alain}, editor = {Jaeger, Dieter and Jung, Ranu}, year = {2014}, note = {DOI: 10.1007/978-1-4614-7320-6\_136-1}, keywords = {Computation by Abstract Devices, Neurobiology, Neurosciences}, pages = {1--7}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MCZXHUZE\\978-1-4614-7320-6_136-1.html:text/html} } @article{tsien_transition_1969, title = {A transition state theory approach to the kinetics of conductance changes in excitable membranes}, volume = {1}, issn = {0022-2631, 1432-1424}, url = {https://link-springer-com.ezp.lib.unimelb.edu.au/article/10.1007/BF01869785}, doi = {10.1007/BF01869785}, abstract = {The kinetics of ionic current mechanisms in excitable membranes are analyzed. It is assumed that there are voltage-dependent reactions occurring in the membrane which are independent of the flow of io}, language = {en}, number = {1}, urldate = {2017-05-23}, journal = {The Journal of Membrane Biology}, author = {Tsien, R. W. and Noble, D.}, month = dec, year = {1969}, pages = {248--273}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZNX6V7TK\\BF01869785.html:text/html;Tsien_Noble (1969) - A transition state theory approach to the kinetics of conductance changes in.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EUPBUREU\\Tsien_Noble (1969) - A transition state theory approach to the kinetics of conductance changes in.pdf:application/pdf} } @article{sakmann_conductance_1984, title = {Conductance properties of single inwardly rectifying potassium channels in ventricular cells from guinea-pig heart.}, volume = {347}, issn = {0022-3751}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1199469/}, abstract = {Single ventricular cells were enzymatically isolated from adult guinea-pig hearts (Isenberg \& Klöckner, 1982). The patch-clamp technique (Hamill, Marty, Neher, Sakmann \& Sigworth, 1981) was used to examine the conductance properties of an inward-rectifying K+ channel present in their sarcolemmal membrane. When the K+ concentration on the extracellular side of the patch was between 10.8 and 300 mM, inward current steps were observed at potentials more negative than the K+ equilibrium potential (EK). At more positive potentials no current steps were detectable, demonstrating the strong rectification of the channel. The zero-current potential extrapolated from the voltage dependence of the inward currents depends on the external K4 concentration [K+]o in a fashion expected for a predominantly K+-selective ion channel. It is shifted by 49 mV for a tenfold change in [K+]o. The conductance of the channel depends on the square root of [K+]o. In approximately symmetrical transmembrane K+ concentrations (145 mM-external K+), the single-channel conductance is 27 pS (at 19-23 degrees C). In normal Tyrode solution (5.4 mM-external K+) we calculate a single-channel conductance of 3.6 pS. The size of inward current steps at a fixed negative membrane potential V increases with [K+]o. The relation between step size and [K+]o shows saturation. Assuming a Michaelis-Menten scheme for binding of permeating K+ to the channel, an apparent binding constant of 210 mM is calculated for a membrane potential of -100 mV. For this potential the current at saturating [K+]o is estimated as 6.5 pA. The rectification of the single-channel conductance at membrane potentials positive to EK occurs within 1.5 ms of stepping the membrane potential from a potential of high conductance to one of low conductance. In addition to the main conductance state, the channel can adopt several substates of conductance. The main state could be the result of the simultaneous opening of four conducting subunits, each of which has a conductance of about 7 pS in 145 mM-external K+. The density of the inward-rectifying K+ channels in the ventricular sarcolemma is 0-10 channel/10 micron2 of surface membrane; the average of twenty-eight patches was 1 channel/1.8 micron2. It is concluded that the inward-rectifying K+ channels mediate the resting K+ conductance of ventricular heart muscle and the current termed IK1 in conventional voltage-clamp experiments.}, urldate = {2017-05-25}, journal = {The Journal of Physiology}, author = {Sakmann, B and Trube, G}, month = feb, year = {1984}, pmid = {6323703}, pmcid = {PMC1199469}, pages = {641--657}, file = {Sakmann_Trube (1984) - Conductance properties of single inwardly rectifying potassium channels in.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\BA66A42C\\Sakmann_Trube (1984) - Conductance properties of single inwardly rectifying potassium channels in.pdf:application/pdf} } @article{snyders_structure_1999, title = {Structure and function of cardiac potassium channels}, volume = {42}, issn = {0008-6363}, url = {https://academic-oup-com.ezp.lib.unimelb.edu.au/cardiovascres/article/42/2/377/278061/Structure-and-function-of-cardiac-potassium}, doi = {10.1016/S0008-6363(99)00071-1}, number = {2}, urldate = {2017-05-26}, journal = {Cardiovascular Research}, author = {Snyders, Dirk J.}, month = may, year = {1999}, pages = {377--390}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\CHRBGEWM\\Structure-and-function-of-cardiac-potassium.html:text/html;Snyders (1999) - Structure and function of cardiac potassium channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5K5M9JH2\\Snyders (1999) - Structure and function of cardiac potassium channels.pdf:application/pdf} } @article{fink_markov_2009, title = {Markov models for ion channels: versatility versus identifiability and speed}, volume = {367}, copyright = {© 2009 The Royal Society}, issn = {1364-503X, 1471-2962}, shorttitle = {Markov models for ion channels}, url = {http://rsta.royalsocietypublishing.org/content/367/1896/2161}, doi = {10.1098/rsta.2008.0301}, abstract = {Markov models (MMs) represent a generalization of Hodgkin–Huxley models. They provide a versatile structure for modelling single channel data, gating currents, state-dependent drug interaction data, exchanger and pump dynamics, etc. This paper uses examples from cardiac electrophysiology to discuss aspects related to parameter estimation. (i) Parameter unidentifiability (found in 9 out of 13 of the considered models) results in an inability to determine the correct layout of a model, contradicting the idea that model structure and parameters provide insights into underlying molecular processes. (ii) The information content of experimental voltage step clamp data is discussed, and a short but sufficient protocol for parameter estimation is presented. (iii) MMs have been associated with high computational cost (owing to their large number of state variables), presenting an obstacle for multicellular whole organ simulations as well as parameter estimation. It is shown that the stiffness of models increases computation time more than the number of states. (iv) Algorithms and software programs are provided for steady-state analysis, analytical solutions for voltage steps and numerical derivation of parameter identifiability. The results provide a new standard for ion channel modelling to further the automation of model development, the validation process and the predictive power of these models.}, language = {en}, number = {1896}, urldate = {2017-06-06}, journal = {Philosophical Transactions of the Royal Society of London A: Mathematical, Physical and Engineering Sciences}, author = {Fink, Martin and Noble, Denis}, month = jun, year = {2009}, pmid = {19414451}, pages = {2161--2179}, file = {Fink_Noble (2009) - Markov models for ion channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\MXGD7IXP\\Fink_Noble (2009) - Markov models for ion channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5HQPQ4M5\\2161.html:text/html} } @article{zeng_two_1995, title = {Two {Components} of the {Delayed} {Rectifier} {K}$^{\textrm{+}}$ {Current} in {Ventricular} {Myocytes} of the {Guinea} {Pig} {Type}}, volume = {77}, copyright = {© 1995 American Heart Association, Inc.}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/77/1/140}, doi = {10.1161/01.RES.77.1.140}, abstract = {Abstract Two distinct delayed rectifier K+ currents, IKr and IKs, were found recently in ventricular cells. We formulated these currents theoretically and investigated their roles in action potential repolarization and the restitution of action potential duration (APD). The Luo-Rudy (L-R) model of the ventricular action potential was used in the simulations. The single delayed rectifier K+ current in the model was replaced by IKr and IKs. Our results show that IKs is the major outward current during the plateau repolarization. A specific block of either IKr or IKs can effectively prolong APD to the same degree. Therefore, either channel provides a target for class III antiarrhythmic drugs. In the simulated guinea pig ventricular cell, complete block of IKr does not result in early afterdepolarizations (EADs). In contrast, {\textgreater}80\% block of IKs results in abnormal repolarization and EADs. This behavior reflects the high IKs-to-IKr density ratio (≈8:1) in this cell and can be reversed (ie, IKr block can cause EADs) by reducing the ratio of Iks to IKr. The computed APD restitution curve is consistent with the experimental behavior, displaying fast APD variation at short diastolic intervals (DIs) and downward shift at longer DIs with the decrease of basic drive cycle length (BCL). Examining the ionic currents and their underlying kinetic processes, we found that activation of both IKr and IKs is the primary determinant of the APD restitution at shorter DIs, with Ca2+ current through L-type channels (ICa) playing a minor role. The rate of APD change depends on the relative densities of IKr and IKs; it increases when the IKr-to-IKs density ratio is large. The BCL-dependent shift of restitution at longer DIs is primarily attributed to long-lasting changes in [Ca2+]i. This in turn causes different degrees of Ca2+-dependent inactivation of ICa and different degrees of Ca2+-dependent conductance of IKs at very long DIs ({\textgreater}5 s) for different BCLs. This BCL dependence of ICa and IKs that is secondary to long-lasting changes in [Ca2+]i is responsible for APD changes at long DIs and can be viewed as a “memory property” of cardiac cells.}, language = {en}, number = {1}, urldate = {2017-06-13}, journal = {Circulation Research}, author = {Zeng, Jinglin and Laurita, Kenneth R. and Rosenbaum, David S. and Rudy, Yoram}, month = jul, year = {1995}, pmid = {7788872}, keywords = {action potential duration, K+ current, optical mapping, repolarization, simulation}, pages = {140--152}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UH4EEXJI\\140.html:text/html} } @article{viswanathan_effects_1999, title = {Effects of \textit{{I}}$_{\textrm{{Kr}}}$ and \textit{{I}}$_{\textrm{{Ks}}}$ {Heterogeneity} on {Action} {Potential} {Duration} and {Its} {Rate} {Dependence}}, volume = {99}, copyright = {Copyright © 1999 by American Heart Association}, issn = {0009-7322, 1524-4539}, url = {http://circ.ahajournals.org.ezp.lib.unimelb.edu.au/content/99/18/2466}, doi = {10.1161/01.CIR.99.18.2466}, abstract = {Background—A growing body of evidence suggests that heterogeneity of ion channel expression and electrophysiological characteristics is an important property of the ventricular myocardium. The 2 components of the delayed rectifier potassium current, IKr (rapid) and IKs (slow), play a dominant role in the repolarization of the action potential and are important determinants of its duration. Methods and Results—In this report, the effects of heterogeneities of IKr and IKs on action potential duration (APD) and its rate dependence (adaptation) are studied with the use of the LRd model of a mammalian ventricular cell. Results demonstrate the importance of IKs density variations in heterogeneity of repolarization. Cells with reduced IKs (eg, mid-myocardial M cells) display long APD and steep dependence of APD on rate. Mechanistically, accumulation of IKs activation and increased sodium calcium exchange current, INaCa, secondary to Na+ accumulation at a fast rate underlie the steep APD-rate relation of these cells. When cells are electrotonically coupled in a multicellular fiber through resistive gap junction, APD differences are reduced. The results demonstrate strong dependence of APD heterogeneity on the degree of intercellular coupling even in the normal physiological range. Highly reduced coupling maximizes APD heterogeneity. Conclusions—Heterogeneity of IKs:IKr density strongly influences APD and its rate dependence. However, in the intact myocardium, the degree of gap-junction coupling may be an important factor that determines the manifestation of APD heterogeneity and dispersion of repolarization. The clinical significance of this study is in the context of repolarization abnormalities and associated arrhythmias (eg, long QT syndrome and torsade de pointes).}, language = {en}, number = {18}, urldate = {2017-06-13}, journal = {Circulation}, author = {Viswanathan, Prakash C. and Shaw, Robin M. and Rudy, Yoram}, month = may, year = {1999}, pmid = {10318671}, keywords = {Action Potentials, arrhythmia, calcium channels, conduction, potassium}, pages = {2466--2474}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7ZAHPP4Z\\2466.html:text/html;Viswanathan et al (1999) - Effects of iI-isubKr-sub and iI-isubKs-sub Heterogeneity on.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZAQVJQA4\\Viswanathan et al (1999) - Effects of iI-isubKr-sub and iI-isubKs-sub Heterogeneity on.pdf:application/pdf} } @article{noble_modeling_2004, title = {Modeling the {Heart}}, volume = {19}, copyright = {© 2004 Int. Union Physiol. Sci./Am. Physiol. Soc.}, issn = {1548-9213, 1548-9221}, url = {http://physiologyonline.physiology.org.ezp.lib.unimelb.edu.au/content/19/4/191}, doi = {10.1152/physiol.00004.2004}, abstract = {Models of the heart have been developed since 1960, starting with the discovery and modeling of potassium channels. The first models of calcium balance were made in the 1980s and have now reached a high degree of physiological detail. During the 1990s, these cell models were incorporated into anatomically detailed tissue and organ models.}, language = {en}, number = {4}, urldate = {2017-06-14}, journal = {Physiology}, author = {Noble, Denis}, month = aug, year = {2004}, pmid = {15304633}, pages = {191--197}, file = {Noble (2004) - Modeling the Heart.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EI7G22ZM\\Noble (2004) - Modeling the Heart.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FE6VWWVA\\191.html:text/html} } @article{nelson_left_2000, title = {Left {Ventricular} or {Biventricular} {Pacing} {Improves} {Cardiac} {Function} at {Diminished} {Energy} {Cost} in {Patients} {With} {Dilated} {Cardiomyopathy} and {Left} {Bundle}-{Branch} {Block}}, volume = {102}, copyright = {Copyright © 2000 by American Heart Association}, issn = {0009-7322, 1524-4539}, url = {http://circ.ahajournals.org.ezp.lib.unimelb.edu.au/content/102/25/3053}, doi = {10.1161/01.CIR.102.25.3053}, abstract = {Background—Left ventricular or biventricular pacing/stimulation can acutely improve systolic function in patients with dilated cardiomyopathy (DCM) and intraventricular conduction delay by resynchronizing contraction. Most heart failure therapies directly enhancing systolic function do so while concomitantly increasing myocardial oxygen consumption (MVO2). We hypothesized that pacing/stimulation, in contrast, incurs systolic benefits without raising energy demand. Methods and Results—Ten DCM patients with left bundle-branch block (ejection fraction 20±3\%, QRS duration179±3 ms, mean±SEM) underwent cardiac catheterization to measure ventricular and aortic pressure, coronary blood flow, arterial–coronary sinus oxygen difference (ΔAVO2), and MV̇O2. Data were measured under sinus rhythm or with left ventricular or biventricular pacing/stimulation at the same heart rate. These results were then contrasted to intravenous dobutamine (n=7) titrated to match systolic changes during LV pacing. Systolic function rose quickly and substantially from LV pacing (18±4\% rise in arterial pulse pressure, which correlates with cardiac output, and 43±6\% increase in dP/dtmax; both P{\textless}0.01). However, ΔAVO2 and MV̇O2 declined −4±2\% and −8±6.5\%, respectively (both P{\textless}0.05). Similar results were obtained with biventricular activation. In contrast, dobutamine raised dP/dtmax 37±6\%, accompanied by a 22±11\% rise in per-beat MV̇O2 (P{\textless}0.05 versus pacing). Conclusions—Ventricular resynchronization by left ventricular or biventricular pacing/stimulation in DCM patients with left bundle-branch block acutely enhances systolic function while modestly lowering energy cost. This should prove valuable for treating DCM patients with basal dyssynchrony.}, language = {en}, number = {25}, urldate = {2017-06-14}, journal = {Circulation}, author = {Nelson, Gregory S. and Berger, Ronald D. and Fetics, Barry J. and Talbot, Maurice and Spinelli, Julio C. and Hare, Joshua M. and Kass, David A.}, month = dec, year = {2000}, pmid = {11120694}, keywords = {bundle-branch block, heart failure, Oxygen, pacing}, pages = {3053--3059}, file = {Nelson et al (2000) - Left Ventricular or Biventricular Pacing Improves Cardiac Function at.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IXW4GJCH\\Nelson et al (2000) - Left Ventricular or Biventricular Pacing Improves Cardiac Function at.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\H8XX94VC\\3053.html:text/html} } @misc{noauthor_inactivation_nodate, title = {Inactivation of calcium current in bull-frog atrial myocytes. - {Campbell} - 1988 - {The} {Journal} of {Physiology} - {Wiley} {Online} {Library}}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1113/jphysiol.1988.sp017250/full}, urldate = {2017-06-22}, file = {Inactivation of calcium current in bull-frog atrial myocytes. - Campbell - 1988 - The Journal of Physiology - Wiley Online Library:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\G3XR5BTD\\full.html:text/html} } @article{borges_effects_2016, title = {Effects of the spike timing-dependent plasticity on the synchronisation in a random {Hodgkin}–{Huxley} neuronal network}, volume = {34}, issn = {1007-5704}, url = {http://www.sciencedirect.com/science/article/pii/S1007570415003366}, doi = {10.1016/j.cnsns.2015.10.005}, abstract = {In this paper, we study the effects of spike timing-dependent plasticity on synchronisation in a network of Hodgkin–Huxley neurons. Neuron plasticity is a flexible property of a neuron and its network to change temporarily or permanently their biochemical, physiological, and morphological characteristics, in order to adapt to the environment. Regarding the plasticity, we consider Hebbian rules, specifically for spike timing-dependent plasticity (STDP), and with regard to network, we consider that the connections are randomly distributed. We analyse the synchronisation and desynchronisation according to an input level and probability of connections. Moreover, we verify that the transition for synchronisation depends on the neuronal network architecture, and the external perturbation level.}, journal = {Communications in Nonlinear Science and Numerical Simulation}, author = {Borges, R. R. and Borges, F. S. and Lameu, E. L. and Batista, A. M. and Iarosz, K. C. and Caldas, I. L. and Viana, R. L. and Sanjuán, M. A. F.}, month = may, year = {2016}, keywords = {Neuronal network, Plasticity, Synchronisation}, pages = {12--22}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\V4ZPFVZB\\S1007570415003366.html:text/html} } @article{perez_analyzing_2016, title = {Analyzing and {Modeling} the {Dysfunction} of {Inhibitory} {Neurons} in {Alzheimer}’s {Disease}}, volume = {11}, issn = {1932-6203}, url = {http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0168800}, doi = {10.1371/journal.pone.0168800}, abstract = {Alzheimer’s disease (AD) is characterized by the abnormal proteolytic processing of amyloid precursor protein, resulting in increased production of a self-aggregating form of beta amyloid (Aβ). Several lines of work on AD patients and transgenic mice with high Aβ levels exhibit altered rhythmicity, aberrant neuronal network activity and hyperexcitability reflected in clusters of hyperactive neurons, and spontaneous epileptic activity. Recent studies highlight that abnormal accumulation of Aβ changes intrinsic properties of inhibitory neurons, which is one of the main reasons underlying the impaired network activity. However, specific cellular mechanisms leading to interneuronal dysfunction are not completely understood. Using extended Hodgkin-Huxley (HH) formalism in conjunction with patch-clamp experiments, we investigate the mechanisms leading to the impaired activity of interneurons. Our detailed analysis indicates that increased Na+ leak explains several observations in inhibitory neurons, including their failure to reliably produce action potentials, smaller action potential amplitude, increased resting membrane potential, and higher membrane depolarization in response to a range of stimuli in a model of APPSWE/PSEN1DeltaE9 (APdE9) AD mice as compared to age-matched control mice. While increasing the conductance of hyperpolarization activated cyclic nucleotide-gated (HCN) ion channel could account for most of the observations, the extent of increase required to reproduce these observations render such changes unrealistic. Furthermore, increasing the conductance of HCN does not account for the observed changes in depolarizability of interneurons from APdE9 mice as compared to those from NTG mice. None of the other pathways tested could lead to all observations about interneuronal dysfunction. Thus we conclude that upregulated sodium leak is the most likely source of impaired interneuronal function.}, number = {12}, urldate = {2017-06-29}, journal = {PLOS ONE}, author = {Perez, Carlos and Ziburkus, Jokubas and Ullah, Ghanim}, month = dec, year = {2016}, keywords = {Action Potentials, Alzheimer disease, Animal behavior, Interneurons, Membrane potential, Mice, Mouse models, Neurons}, pages = {e0168800}, file = {Perez et al (2016) - Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7FAE98CB\\Perez et al (2016) - Analyzing and Modeling the Dysfunction of Inhibitory Neurons in Alzheimer’s.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FC6WNCCG\\article.html:text/html} } @article{niven_energy_2008, title = {Energy limitation as a selective pressure on the evolution of sensory systems}, volume = {211}, issn = {0022-0949}, doi = {10.1242/jeb.017574}, abstract = {Evolution of animal morphology, physiology and behaviour is shaped by the selective pressures to which they are subject. Some selective pressures act to increase the benefits accrued whilst others act to reduce the costs incurred, affecting the cost/benefit ratio. Selective pressures therefore produce a trade-off between costs and benefits that ultimately influences the fitness of the whole organism. The nervous system has a unique position as the interface between morphology, physiology and behaviour; the final output of the nervous system is the behaviour of the animal, which is a product of both its morphology and physiology. The nervous system is under selective pressure to generate adaptive behaviour, but at the same time is subject to costs related to the amount of energy that it consumes. Characterising this trade-off between costs and benefits is essential to understanding the evolution of nervous systems, including our own. Within the nervous system, sensory systems are the most amenable to analysing costs and benefits, not only because their function can be more readily defined than that of many central brain regions and their benefits quantified in terms of their performance, but also because recent studies of sensory systems have begun to directly assess their energetic costs. Our review focuses on the visual system in particular, although the principles we discuss are equally applicable throughout the nervous system. Examples are taken from a wide range of sensory modalities in both vertebrates and invertebrates. We aim to place the studies we review into an evolutionary framework. We combine experimentally determined measures of energy consumption from whole retinas of rabbits and flies with intracellular measurements of energy consumption from single fly photoreceptors and recently constructed energy budgets for neural processing in rats to assess the contributions of various components to neuronal energy consumption. Taken together, these studies emphasize the high costs of maintaining neurons at rest and whilst signalling. A substantial proportion of neuronal energy consumption is related to the movements of ions across the neuronal cell membrane through ion channels, though other processes such as vesicle loading and transmitter recycling also consume energy. Many of the energetic costs within neurons are linked to 3Na(+)/2K(+) ATPase activity, which consumes energy to pump Na(+) and K(+) ions across the cell membrane and is essential for the maintenance of the resting potential and its restoration following signalling. Furthermore, recent studies in fly photoreceptors show that energetic costs can be related, via basic biophysical relationships, to their function. These findings emphasize that neurons are subject to a law of diminishing returns that severely penalizes excess functional capacity with increased energetic costs. The high energetic costs associated with neural tissue favour energy efficient coding and wiring schemes, which have been found in numerous sensory systems. We discuss the role of these efficient schemes in reducing the costs of information processing. Assessing evidence from a wide range of vertebrate and invertebrate examples, we show that reducing energy expenditure can account for many of the morphological features of sensory systems and has played a key role in their evolution.}, language = {eng}, number = {Pt 11}, journal = {The Journal of Experimental Biology}, author = {Niven, Jeremy E. and Laughlin, Simon B.}, month = jun, year = {2008}, pmid = {18490395}, keywords = {Animals, Biological Evolution, Brain, Diptera, Energy Metabolism, Fishes, Mammals, Photoreceptor Cells, Rabbits, Retina, Selection, Genetic, Vision, Ocular, Visual Perception}, pages = {1792--1804} } @article{rudy_computational_2006, title = {Computational biology in the study of cardiac ion channels and cell electrophysiology}, volume = {39}, issn = {1469-8994, 0033-5835}, url = {https://www-cambridge-org.ezp.lib.unimelb.edu.au/core/journals/quarterly-reviews-of-biophysics/article/computational-biology-in-the-study-of-cardiac-ion-channels-and-cell-electrophysiology/911294871CFB1B0F119252B67BA74E64}, doi = {10.1017/S0033583506004227}, abstract = {1. Prologue 582. The Hodgkin–Huxley formalism for computing the action potential 592.1 The axon action potential model 592.2 Cardiac action potential models 623. Ion-channel based formulation of the action potential 653.1 Ion-channel structure 653.2 Markov models of ion-channel kinetics 663.3 Role of selected ion channels in rate dependence of the cardiac action potential 713.4 Physiological implications of IKs subunit interaction 773.5 Mechanism of cardiac action potential rate-adaptation is species dependent 784. Simulating ion-channel mutations and their electrophysiological consequences 814.1 Mutations in SCN5A, the gene that encodes the cardiac sodium channel 824.1.1 The ΔKPQ mutation and LQT3 824.1.2 SCN5A mutation that underlies a dual phenotype 874.2 Mutations in HERG, the gene that encodes IKr: re-examination of the ‘gain of function/loss of function’ concept 944.3 Role of IKs as ‘repolarization reserve’ 1005. Modeling cell signaling in electrophysiology 1025.1 CaMKII regulation of the Ca2+ transient 1025.2 The β-adrenergic signaling cascade 1056. Epilogue 1077. Acknowledgments 1088. References 109The cardiac cell is a complex biological system where various processes interact to generate electrical excitation (the action potential, AP) and contraction. During AP generation, membrane ion channels interact nonlinearly with dynamically changing ionic concentrations and varying transmembrane voltage, and are subject to regulatory processes. In recent years, a large body of knowledge has accumulated on the molecular structure of cardiac ion channels, their function, and their modification by genetic mutations that are associated with cardiac arrhythmias and sudden death. However, ion channels are typically studied in isolation (in expression systems or isolated membrane patches), away from the physiological environment of the cell where they interact to generate the AP. A major challenge remains the integration of ion-channel properties into the functioning, complex and highly interactive cell system, with the objective to relate molecular-level processes and their modification by disease to whole-cell function and clinical phenotype. In this article we describe how computational biology can be used to achieve such integration. We explain how mathematical (Markov) models of ion-channel kinetics are incorporated into integrated models of cardiac cells to compute the AP. We provide examples of mathematical (computer) simulations of physiological and pathological phenomena, including AP adaptation to changes in heart rate, genetic mutations in SCN5A and HERG genes that are associated with fatal cardiac arrhythmias, and effects of the CaMKII regulatory pathway and β-adrenergic cascade on the cell electrophysiological function.}, number = {1}, urldate = {2017-06-29}, journal = {Quarterly Reviews of Biophysics}, author = {Rudy, Yoram and Silva, Jonathan R.}, month = feb, year = {2006}, pages = {57--116}, file = {Rudy_Silva (2006) - Computational biology in the study of cardiac ion channels and cell.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\5WEKBS85\\Rudy_Silva (2006) - Computational biology in the study of cardiac ion channels and cell.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\DZ7SFIEH\\911294871CFB1B0F119252B67BA74E64.html:text/html} } @article{reuter_ion_1984, title = {Ion channels in cardiac cell membranes}, volume = {46}, url = {http://www.annualreviews.org/doi/pdf/10.1146/annurev.ph.46.030184.002353}, number = {1}, urldate = {2017-07-03}, journal = {Annual review of physiology}, author = {Reuter, Harald}, year = {1984}, pages = {473--484}, file = {annurev.ph.46.030184.002353.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WHUFBPDZ\\annurev.ph.46.030184.002353.pdf:application/pdf} } @misc{noauthor_characterization_nodate, title = {Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization.}, url = {https://www-ncbi-nlm-nih-gov.ezp.lib.unimelb.edu.au/pmc/articles/PMC1160853/}, urldate = {2017-07-03}, file = {Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization.:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EF29K9ZM\\PMC1160853.html:text/html} } @article{yue_characterization_1996, title = {Characterization of an ultrarapid delayed rectifier potassium channel involved in canine atrial repolarization.}, volume = {496}, issn = {0022-3751}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1160853/}, abstract = {1. Depolarizing pulses positive to 0 mV elicit a transient outward current (Ito) and a sustained 'pedestal' current in canine atrial myocytes. The pedestal current was highly sensitive to 4-aminopyridine (4-AP) and TEA, with 50\% inhibitory concentrations (EC50) of 5.3 +/- 0.7 and 307 +/- 25 microM, respectively. When the pedestal current was separated from Ito with prepulses or by studying current sensitive to 10 mM TEA, it showed very rapid activation and deactivation. We therefore designated the current IKur,d, for 'ultrarapid delayed rectifier, dog'. IKur,d inactivation was bi-exponential, with mean time constants of 609 +/- 91 and 5563 +/- 676 ms during a 20 s pulse to +40 mV. 2. The reversal potential of IKur,d tail currents are dependent on extracellular potassium concentration ([K+]o; slope, 54.7 mV decade-1). The envelope of tails test was satisfied and the current inwardly rectified at {\textgreater} or = +40 mV. The current was insensitive to E-4031, dendrotoxin and chloride substitution, but was inhibited by barium, with an EC50 of 1.65 mM. Lanthanum ions caused a positive shift in voltage dependence without producing direct inhibition. 3. Single-channel activity was observed in cell-attached, inside-out and outside-out patches. Upon depolarization from -50 to +30 mV, single channels had similar time constants and [K+]o dependence to whole-cell current. Channel open probability (Po) increased with depolarization in a saturable fashion and the Po-voltage relation had a half-activation voltage and slope factor similar to whole-cell IKur,d. 4. Unitary channel current was linearly related to depolarization potential to +40 mV; at more positive potentials, inward rectification occurred. The unitary conductance was 20.3 and 35.5 pS for an [K+]o of 5.4 and 130 mM, respectively. Single-channel activity was strongly inhibited by 50 microM 4-AP or 10 mM TEA. Both 4-AP and TEA decreased open time, suggesting open-channel block. 5. Selective inhibition of IKur,d with 50 microM 4-AP or 0.3-5 mM TEA prolonged canine atrial action potentials, indicating that IKur,d contributes to canine atrial repolarization. The single-channel and macroscopic properties of IKur,d have many similarities to those of currents carried by Kv3.1 cloned channels and our findings thus suggest a possible role for Kv3.1 channels in cardiac repolarization.}, number = {Pt 3}, journal = {The Journal of Physiology}, author = {Yue, L and Feng, J and Li, G R and Nattel, S}, month = nov, year = {1996}, pmid = {8930833}, pmcid = {PMC1160853}, pages = {647--662}, file = {Yue et al (1996) - Characterization of an ultrarapid delayed rectifier potassium channel involved.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\74PPP59R\\Yue et al (1996) - Characterization of an ultrarapid delayed rectifier potassium channel involved.pdf:application/pdf} } @article{armstrong_na_2006, title = {Na channel inactivation from open and closed states}, volume = {103}, issn = {0027-8424, 1091-6490}, url = {http://www.pnas.org/content/103/47/17991}, doi = {10.1073/pnas.0607603103}, abstract = {A sodium channel is composed of four similar domains, each containing a highly charged S4 helix that is driven outward (activates) in response to a depolarization. Functionally, the channel has two gates, called activation gate (a gate) and inactivation gate (I gate), both of which must be open for conduction to occur. The cytoplasmically located a gate opens after a depolarization has activated the S4s of (probably) all four domains. The I gate consists of a cytoplasmically located inactivation “particle” and a receptor for it in the channel. The receptor becomes available after some degree of S4 activation, and the particle diffuses in to inactivate the channel. The I gate usually closes when the a gate is open [open-state inactivation (Osi)] but also can close before the channel reaches the conducting state. This “closed-state inactivation” (Csi) is studied quantitatively in this paper to determine the degree of S4 activation required for (i) opening the a gate, and (ii) permitting the I gate to close. Csi is most prominent for small depolarizations, during which occupancy of the partially activated closed states is prolonged. Large depolarizations drive the S4s outward quickly, minimizing the duration of closed-state occupancy and making Csi small and Osi large. Based on these data and evidence in the literature, it is concluded that opening the a gate requires S4 activation in domains 1–3, with partial activation of the S4 of domain 4. Csi requires only S4 activation of domains 3 and 4, which does not open the a gate.}, language = {en}, number = {47}, urldate = {2017-07-06}, journal = {Proceedings of the National Academy of Sciences}, author = {Armstrong, Clay M.}, month = nov, year = {2006}, pmid = {17101981}, keywords = {activation}, pages = {17991--17996}, file = {Armstrong (2006) - Na channel inactivation from open and closed states.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\4WJN7ZID\\Armstrong (2006) - Na channel inactivation from open and closed states.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZERMWKEI\\17991.html:text/html} } @article{horn_immobilizing_2000, title = {Immobilizing the {Moving} {Parts} of {Voltage}-{Gated} {Ion} {Channels}}, volume = {116}, copyright = {© 2000 The Rockefeller University Press}, issn = {0022-1295, 1540-7748}, url = {http://jgp.rupress.org.ezp.lib.unimelb.edu.au/content/116/3/461}, doi = {10.1085/jgp.116.3.461}, abstract = {Voltage-gated ion channels have at least two classes of moving parts, voltage sensors that respond to changes in the transmembrane potential and gates that create or deny permeant ions access to the conduction pathway. To explore the coupling between voltage sensors and gates, we have systematically immobilized each using a bifunctional photoactivatable cross-linker, benzophenone-4-carboxamidocysteine methanethiosulfonate, that can be tethered to cysteines introduced into the channel protein by mutagenesis. To validate the method, we first tested it on the inactivation gate of the sodium channel. The benzophenone-labeled inactivation gate of the sodium channel can be trapped selectively either in an open or closed state by ultraviolet irradiation at either a hyperpolarized or depolarized voltage, respectively. To verify that ultraviolet light can immobilize S4 segments, we examined its relative effects on ionic and gating currents in Shaker potassium channels, labeled at residue 359 at the extracellular end of the S4 segment. As predicted by the tetrameric stoichiometry of these potassium channels, ultraviolet irradiation reduces ionic current by approximately the fourth power of the gating current reduction, suggesting little cooperativity between the movements of individual S4 segments. Photocross-linking occurs preferably at hyperpolarized voltages after labeling residue 359, suggesting that depolarization moves the benzophenone adduct out of a restricted environment. Immobilization of the S4 segment of the second domain of sodium channels prevents channels from opening. By contrast, photocross-linking the S4 segment of the fourth domain of the sodium channel has effects on both activation and inactivation. Our results indicate that specific voltage sensors of the sodium channel play unique roles in gating, and suggest that movement of one voltage sensor, the S4 segment of domain 4, is at least a two-step process, each step coupled to a different gate.}, language = {en}, number = {3}, urldate = {2017-07-06}, journal = {The Journal of General Physiology}, author = {Horn, Richard and Ding, Shinghua and Gruber, Hermann J.}, month = sep, year = {2000}, pmid = {10962021}, keywords = {benzophenone, cysteine mutagenesis, S4 segment, Shaker potassium channel, sodium channel}, pages = {461--476}, file = {Horn et al (2000) - Immobilizing the Moving Parts of Voltage-Gated Ion Channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UPBCH8MH\\Horn et al (2000) - Immobilizing the Moving Parts of Voltage-Gated Ion Channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IP32282C\\461.html:text/html} } @article{vandenberg_sodium_1991, title = {A sodium channel gating model based on single channel, macroscopic ionic, and gating currents in the squid giant axon}, volume = {60}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349591821865}, doi = {10.1016/S0006-3495(91)82186-5}, abstract = {Sodium channel gating behavior was modeled with Markovian models fitted to currents from the cut-open squid giant axon in the absence of divalent cations. Optimum models were selected with maximum likelihood criteria using single-channel data, then models were refined and extended by simultaneous fitting of macroscopic ionic currents, ON and OFF gating currents, and single-channel first latency densities over a wide voltage range. Best models have five closed states before channel opening, with inactivation from at least one closed state as well as the open state. Forward activation rate constants increase with depolarization, and deactivation rate constants increase with hyperpolarization. Rates of inactivation from the open or closed states are generally slower than activation or deactivation rates and show little or no voltage dependence. Channels tend to reopen several times before inactivating. Macroscopic rates of activation and inactivation result from a combination of closed, open and inactivated state transitions. At negative potentials the time to first opening dominates the macroscopic current due to slow activation rates compared with deactivation rates: channels tend to reopen rarely, and often inactivate from closed states before they reopen. At more positive potentials, the time to first opening and burst duration together produce the macroscopic current.}, number = {6}, journal = {Biophysical Journal}, author = {Vandenberg, C. A. and Bezanilla, F.}, month = dec, year = {1991}, pages = {1511--1533}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7RQ3966Z\\S0006349591821865.html:text/html;Vandenberg_Bezanilla (1991) - A sodium channel gating model based on single channel, macroscopic ionic, and.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\8JMPXCR3\\Vandenberg_Bezanilla (1991) - A sodium channel gating model based on single channel, macroscopic ionic, and.pdf:application/pdf} } @article{armstrong_ionic_1974, title = {Ionic pores, gates, and gating currents}, volume = {7}, issn = {1469-8994, 0033-5835}, url = {https://www-cambridge-org.ezp.lib.unimelb.edu.au/core/journals/quarterly-reviews-of-biophysics/article/ionic-pores-gates-and-gating-currents/9BFA9DBAEE4A0A2B562EF53899260790}, doi = {10.1017/S0033583500001402}, abstract = {The current phase of axon physiology began with the invention of the voltage clamp by Cole (1949) and its use by Hodgkin \& Huxley (1952d) to produce an astonishingly complete analysis of the ionic permeabilities that are responsible for the action potential. Their description did notcontain much in the way of molecular detail, and left open such questions as whether ions cross the membrane by way of pores or carriers, and the nature of the ‘gating‘ processes that increase ordecrease ion permeability in response to changes of the membrane potential. In the last few years our picture of the ionicchannels has grown considerably more tangible, though it still falls far short of a detailed molecular description. This article describes this sharpened picture and reviews the evidence for it. The viewpoint expressed is a very personal one, andno attempt has been made to review the literature of axonology comprehensively.}, number = {2}, urldate = {2017-07-06}, journal = {Quarterly Reviews of Biophysics}, author = {Armstrong, Clay M.}, month = may, year = {1974}, pages = {179--209}, file = {Armstrong (1974) - Ionic pores, gates, and gating currents.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\D57TED6G\\Armstrong (1974) - Ionic pores, gates, and gating currents.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\S4C2HZN2\\9BFA9DBAEE4A0A2B562EF53899260790.html:text/html} } @article{noauthor_abstracts_1973, title = {Abstracts of {Papers} {Presented} at the {Marine} {Biological} {Laboratory}}, volume = {145}, issn = {0006-3185}, url = {http://www.jstor.org.ezp.lib.unimelb.edu.au/stable/1540049}, number = {2}, journal = {Biological Bulletin}, year = {1973}, pages = {423--461} } @article{bezanilla_gating_1974, title = {Gating {Currents} of the {Sodium} {Channels}: {Three} {Ways} to {Block} {Them}}, volume = {183}, copyright = {1974 by the American Association for the Advancement of Science}, issn = {0036-8075, 1095-9203}, shorttitle = {Gating {Currents} of the {Sodium} {Channels}}, url = {http://science.sciencemag.org.ezp.lib.unimelb.edu.au/content/183/4126/753}, doi = {10.1126/science.183.4126.753}, abstract = {Preceding the opening of the sodium channels of axon membrane there is a small outward current, gating current, that is probably associated with the molecular rearrangements that open the channels. Gating current is reversibly blocked by three procedures that block the sodium current: (i) internal perfusion with zinc ions, (ii) inactivation of sodium conductance by brief depolarization, and (iii) prolonged depolarization.}, language = {en}, number = {4126}, urldate = {2017-07-06}, journal = {Science}, author = {Bezanilla, Francisco and Armstrong, Clay M.}, month = feb, year = {1974}, pmid = {4821243}, pages = {753--754}, file = {Bezanilla_Armstrong (1974) - Gating Currents of the Sodium Channels.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UKU48PVX\\Bezanilla_Armstrong (1974) - Gating Currents of the Sodium Channels.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\33I8MSNA\\753.html:text/html} } @article{ermentrout_simplifying_2001, title = {Simplifying and reducing complex models}, url = {http://www.math.pitt.edu/~bard/pubs/s2.pdf}, urldate = {2017-08-01}, journal = {Computational Modeling of Genetic and Biochemical Networks. MIT Press, Cambridge, MA}, author = {Ermentrout, Bard}, year = {2001}, pages = {307--323}, file = {s2.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\B6PFME82\\s2.pdf:application/pdf} } @article{crampin_mathematical_2004, series = {New approaches to modelling and analysis of biochemical reactions, pathways and networks}, title = {Mathematical and computational techniques to deduce complex biochemical reaction mechanisms}, volume = {86}, issn = {0079-6107}, url = {http://www.sciencedirect.com/science/article/pii/S007961070400046X}, doi = {10.1016/j.pbiomolbio.2004.04.002}, abstract = {Time series data can now be routinely collected for biochemical reaction pathways, and recently, several methods have been proposed to infer reaction mechanisms for metabolic pathways and networks. In this paper we provide a survey of mathematical techniques for determining reaction mechanisms for time series data on the concentration or abundance of different reacting components, with little prior information about the pathways involved.}, number = {1}, journal = {Progress in Biophysics and Molecular Biology}, author = {Crampin, E. J. and Schnell, S. and McSharry, P. E.}, month = sep, year = {2004}, pages = {77--112}, file = {Crampin et al (2004) - Mathematical and computational techniques to deduce complex biochemical.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\QJRPMHBV\\Crampin et al (2004) - Mathematical and computational techniques to deduce complex biochemical.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\FRBBIVCC\\S007961070400046X.html:text/html} } @article{finkelstein_computational_2004, title = {Computational challenges of systems biology}, volume = {37}, issn = {0018-9162}, doi = {10.1109/MC.2004.1297236}, abstract = {Progress in the study of biological systems such as the heart, brain, and liver will require computer scientists to work closely with life scientists and mathematicians. Computer science will play a key role in shaping the new discipline of systems biology and addressing the significant computational challenges it poses.}, number = {5}, journal = {Computer}, author = {Finkelstein, A. and Hetherington, J. and Li, Linzhong and Margoninski, O. and Saffrey, P. and Seymour, R. and Warner, A.}, month = may, year = {2004}, keywords = {bioinformatics, Biological system modeling, Biological systems, Biology, biology computing, DNA, DNA sequences, entity-relationship model, entity-relationship modelling, Genetics, Genomics, Heart, high-level information model, Molecular biology, molecular biophysics, Physiology, Proteins, proteins generation, RNA synthesis, Systems Biology}, pages = {26--33}, file = {Finkelstein et al (2004) - Computational challenges of systems biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\THAFZ34S\\Finkelstein et al (2004) - Computational challenges of systems biology.pdf:application/pdf;IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\35DC3HI4\\1297236.html:text/html} } @article{babtie_how_2017, title = {How to deal with parameters for whole-cell modelling}, volume = {14}, copyright = {© 2017 The Author(s). http://royalsocietypublishing.org/licencePublished by the Royal Society. All rights reserved.}, issn = {1742-5689, 1742-5662}, url = {http://rsif.royalsocietypublishing.org/content/14/133/20170237}, doi = {10.1098/rsif.2017.0237}, abstract = {Dynamical systems describing whole cells are on the verge of becoming a reality. But as models of reality, they are only useful if we have realistic parameters for the molecular reaction rates and cell physiological processes. There is currently no suitable framework to reliably estimate hundreds, let alone thousands, of reaction rate parameters. Here, we map out the relative weaknesses and promises of different approaches aimed at redressing this issue. While suitable procedures for estimation or inference of the whole (vast) set of parameters will, in all likelihood, remain elusive, some hope can be drawn from the fact that much of the cellular behaviour may be explained in terms of smaller sets of parameters. Identifying such parameter sets and assessing their behaviour is now becoming possible even for very large systems of equations, and we expect such methods to become central tools in the development and analysis of whole-cell models.}, language = {en}, number = {133}, urldate = {2017-08-10}, journal = {Journal of The Royal Society Interface}, author = {Babtie, Ann C. and Stumpf, Michael P. H.}, month = aug, year = {2017}, pages = {20170237}, file = {Babtie_Stumpf (2017) - How to deal with parameters for whole-cell modelling.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\H8WEGC3I\\Babtie_Stumpf (2017) - How to deal with parameters for whole-cell modelling.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2TEQQE3E\\20170237.html:text/html} } @article{shiferaw_mechanism_2017, title = {Mechanism for {Triggered} {Waves} in {Atrial} {Myocytes}}, volume = {113}, issn = {0006-3495}, url = {http://www.cell.com/biophysj/abstract/S0006-3495(17)30676-8}, doi = {10.1016/j.bpj.2017.06.026}, language = {English}, number = {3}, urldate = {2017-08-15}, journal = {Biophysical Journal}, author = {Shiferaw, Yohannes and Aistrup, Gary L. and Wasserstrom, J. Andrew}, month = aug, year = {2017}, pmid = {28793220}, pages = {656--670}, file = {Shiferaw et al (2017) - Mechanism for Triggered Waves in Atrial Myocytes.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VDXHMJ2H\\Shiferaw et al (2017) - Mechanism for Triggered Waves in Atrial Myocytes.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JBDNMS36\\S0006-3495(17)30676-8.html:text/html} } @article{dano_reduction_2006, title = {Reduction of a biochemical model with preservation of its basic dynamic properties}, volume = {273}, issn = {1742-4658}, url = {http://onlinelibrary.wiley.com.ezp.lib.unimelb.edu.au/doi/10.1111/j.1742-4658.2006.05485.x/abstract}, doi = {10.1111/j.1742-4658.2006.05485.x}, abstract = {The complexity of full-scale metabolic models is a major obstacle for their effective use in computational systems biology. The aim of model reduction is to circumvent this problem by eliminating parts of a model that are unimportant for the properties of interest. The choice of reduction method is influenced both by the type of model complexity and by the objective of the reduction; therefore, no single method is superior in all cases. In this study we present a comparative study of two different methods applied to a 20D model of yeast glycolytic oscillations. Our objective is to obtain biochemically meaningful reduced models, which reproduce the dynamic properties of the 20D model. The first method uses lumping and subsequent constrained parameter optimization. The second method is a novel approach that eliminates variables not essential for the dynamics. The applications of the two methods result in models of eight (lumping), six (elimination) and three (lumping followed by elimination) dimensions. All models have similar dynamic properties and pin-point the same interactions as being crucial for generation of the oscillations. The advantage of the novel method is that it is algorithmic, and does not require input in the form of biochemical knowledge. The lumping approach, however, is better at preserving biochemical properties, as we show through extensive analyses of the models.}, language = {en}, number = {21}, journal = {FEBS Journal}, author = {Danø, Sune and Madsen, Mads F. and Schmidt, Henning and Cedersund, Gunnar}, month = nov, year = {2006}, keywords = {core model, Glycolysis, Hopf bifurcation, model optimization, model reduction}, pages = {4862--4877}, file = {Danø et al (2006) - Reduction of a biochemical model with preservation of its basic dynamic.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AS8WE2ES\\Danø et al (2006) - Reduction of a biochemical model with preservation of its basic dynamic.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\UECXATMP\\abstract.html:text/html} } @article{wolf_effect_2000, title = {Effect of cellular interaction on glycolytic oscillations in yeast: a theoretical investigation}, volume = {345}, copyright = {The Biochemical Society, London © 2000}, issn = {0264-6021, 1470-8728}, shorttitle = {Effect of cellular interaction on glycolytic oscillations in yeast}, url = {http://www.biochemj.org.ezp.lib.unimelb.edu.au/content/345/2/321}, doi = {10.1042/bj3450321}, abstract = {On the basis of a detailed model of yeast glycolysis, the effect of intercellular coupling on the oscillatory dynamics is analysed theoretically. The model includes the main steps of anaerobic glycolysis, and the production of ethanol and glycerol. Transmembrane diffusion of acetaldehyde is included, since it has been hypothesized that this substance mediates the interaction. Depending on the kinetic parameters, the single-cell model shows both stationary and oscillatory behaviour. This agrees with experimental data with respect to metabolite concentrations and phase shifts. The inclusion of intercellular coupling leads to a variety of dynamical modes, such as synchronous oscillations, and different kinds of asynchronous behaviour. These oscillations can co-exist, leading to bi- and tri-rhythmicity. The corresponding parameter regions have been identified by a bifurcation analysis. The oscillatory dynamics of synchronized cell populations are investigated by calculating the phase responses to acetaldehyde pulses. Simulations are performed with respect to the synchronization of two subpopulations that are oscillating out of phase before mixing. The effect of the various processes on synchronization is characterized quantitatively. While continuous exchange of acetaldehyde might synchronize the oscillations for appropriate sets of parameter values, the calculated synchronization time is longer than that observed experimentally. It is concluded either that, in addition to the transmembrane exchange of acetaldehyde, other processes may contribute to intercellular coupling, or that intracellular regulatory feedback plays a role in the acceleration of the synchronization.}, language = {en}, number = {2}, urldate = {2017-08-22}, journal = {Biochemical Journal}, author = {Wolf, Jana and Heinrich, Reinhart}, month = jan, year = {2000}, pmid = {10702114}, pages = {321--334}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\E7E92C4G\\321.html:text/html;Wolf_Heinrich (2000) - Effect of cellular interaction on glycolytic oscillations in yeast.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WATBI4HB\\Wolf_Heinrich (2000) - Effect of cellular interaction on glycolytic oscillations in yeast.pdf:application/pdf} } @article{rao_model_2014, title = {A model reduction method for biochemical reaction networks}, volume = {8}, issn = {1752-0509}, url = {https://doi.org/10.1186/1752-0509-8-52}, doi = {10.1186/1752-0509-8-52}, abstract = {In this paper we propose a model reduction method for biochemical reaction networks governed by a variety of reversible and irreversible enzyme kinetic rate laws, including reversible Michaelis-Menten and Hill kinetics. The method proceeds by a stepwise reduction in the number of complexes, defined as the left and right-hand sides of the reactions in the network. It is based on the Kron reduction of the weighted Laplacian matrix, which describes the graph structure of the complexes and reactions in the network. It does not rely on prior knowledge of the dynamic behaviour of the network and hence can be automated, as we demonstrate. The reduced network has fewer complexes, reactions, variables and parameters as compared to the original network, and yet the behaviour of a preselected set of significant metabolites in the reduced network resembles that of the original network. Moreover the reduced network largely retains the structure and kinetics of the original model.}, journal = {BMC Systems Biology}, author = {Rao, Shodhan and der Schaft, Arjan van and Eunen, Karen van and Bakker, Barbara M. and Jayawardhana, Bayu}, month = may, year = {2014}, keywords = {Complex graph, Enzyme kinetics, Kinetic models, Rat liver beta oxidation, Weighted Laplacian, Yeast glycolysis}, pages = {52}, annote = {Pages 52 in PDF}, file = {Rao et al (2014) - A model reduction method for biochemical reaction networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\AZ4S9SNM\\Rao et al (2014) - A model reduction method for biochemical reaction networks.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\7IKSAKC6\\1752-0509-8-52.html:text/html} } @misc{liu_approach_2013, type = {Research article}, title = {An {Approach} for {Model} {Reduction} of {Biochemical} {Networks}}, url = {https://www.hindawi.com/archive/2013/263973/}, abstract = {Biochemical networks are not only complex but also extremely large. The dynamic biological model of great complexity resulting in a large number of parameters is a main difficulty for optimization and control processes. In practice, it is highly desirable to further simplify the structure of biological models for the sake of reducing computational cost or simplification for the task of system analysis. This paper considers the S-system model used for describing the response of biochemical networks. By introducing the technique of singular value decomposition (SVD), we are able to identify the major state variables and parameters and eliminate unimportant metabolites and the corresponding signal transduction pathways. The model reduction by multiobjective analysis integrates the criteria of reactive weight, sensitivity, and flux analyses to obtain a reduced model in a systematic way. The resultant model is closed to the original model in performance but with a simpler structure. Representative numerical examples are illustrated to prove feasibility of the proposed method.}, language = {en}, urldate = {2017-08-22}, journal = {Computational Biology Journal}, author = {Liu, Yen-Chang and Lin, Chun-Liang and Chuang, Chia-Hua}, year = {2013}, note = {DOI: 10.1155/2013/263973}, file = {Liu et al (2013) - An Approach for Model Reduction of Biochemical Networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\3DBHCSGR\\Liu et al (2013) - An Approach for Model Reduction of Biochemical Networks.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\34DENQQU\\263973.html:application/xhtml+xml} } @article{radulescu_reduction_2012, title = {Reduction of dynamical biochemical reactions networks in computational biology}, volume = {3}, issn = {1664-8021}, url = {http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3400272/}, doi = {10.3389/fgene.2012.00131}, abstract = {Biochemical networks are used in computational biology, to model mechanistic details of systems involved in cell signaling, metabolism, and regulation of gene expression. Parametric and structural uncertainty, as well as combinatorial explosion are strong obstacles against analyzing the dynamics of large models of this type. Multiscaleness, an important property of these networks, can be used to get past some of these obstacles. Networks with many well separated time scales, can be reduced to simpler models, in a way that depends only on the orders of magnitude and not on the exact values of the kinetic parameters. The main idea used for such robust simplifications of networks is the concept of dominance among model elements, allowing hierarchical organization of these elements according to their effects on the network dynamics. This concept finds a natural formulation in tropical geometry. We revisit, in the light of these new ideas, the main approaches to model reduction of reaction networks, such as quasi-steady state (QSS) and quasi-equilibrium approximations (QE), and provide practical recipes for model reduction of linear and non-linear networks. We also discuss the application of model reduction to the problem of parameter identification, via backward pruning machine learning techniques.}, journal = {Frontiers in Genetics}, author = {Radulescu, O. and Gorban, A. N. and Zinovyev, A. and Noel, V.}, month = jul, year = {2012}, pmid = {22833754}, pmcid = {PMC3400272}, file = {Radulescu et al (2012) - Reduction of dynamical biochemical reactions networks in computational biology.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JQ5XA5AV\\Radulescu et al (2012) - Reduction of dynamical biochemical reactions networks in computational biology.pdf:application/pdf} } @article{bueno-orovio_na/k_2014, title = {Na/{K} pump regulation of cardiac repolarization: insights from a systems biology approach}, volume = {466}, issn = {0031-6768, 1432-2013}, shorttitle = {Na/{K} pump regulation of cardiac repolarization}, url = {https://link-springer-com.ezp.lib.unimelb.edu.au/article/10.1007/s00424-013-1293-1}, doi = {10.1007/s00424-013-1293-1}, abstract = {The sodium-potassium pump is widely recognized as the principal mechanism for active ion transport across the cellular membrane of cardiac tissue, being responsible for the creation and maintenance of the transarcolemmal sodium and potassium gradients, crucial for cardiac cell electrophysiology. Importantly, sodium-potassium pump activity is impaired in a number of major diseased conditions, including ischemia and heart failure. However, its subtle ways of action on cardiac electrophysiology, both directly through its electrogenic nature and indirectly via the regulation of cell homeostasis, make it hard to predict the electrophysiological consequences of reduced sodium-potassium pump activity in cardiac repolarization. In this review, we discuss how recent studies adopting the systems biology approach, through the integration of experimental and modeling methodologies, have identified the sodium-potassium pump as one of the most important ionic mechanisms in regulating key properties of cardiac repolarization and its rate dependence, from subcellular to whole organ levels. These include the role of the pump in the biphasic modulation of cellular repolarization and refractoriness, the rate control of intracellular sodium and calcium dynamics and therefore of the adaptation of repolarization to changes in heart rate, as well as its importance in regulating pro-arrhythmic substrates through modulation of dispersion of repolarization and restitution. Theoretical findings are consistent across a variety of cell types and species including human, and widely in agreement with experimental findings. The novel insights and hypotheses on the role of the pump in cardiac electrophysiology obtained through this integrative approach could eventually lead to novel therapeutic and diagnostic strategies.}, language = {en}, number = {2}, urldate = {2017-08-25}, journal = {Pflügers Archiv - European Journal of Physiology}, author = {Bueno-Orovio, Alfonso and Sánchez, Carlos and Pueyo, Esther and Rodriguez, Blanca}, month = feb, year = {2014}, pages = {183--193}, file = {Bueno-Orovio et al (2014) - Na-K pump regulation of cardiac repolarization.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\GD7XD3P6\\Bueno-Orovio et al (2014) - Na-K pump regulation of cardiac repolarization.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6EE5349E\\s00424-013-1293-1.html:text/html} } @article{ohara_simulation_2011, title = {Simulation of the {Undiseased} {Human} {Cardiac} {Ventricular} {Action} {Potential}: {Model} {Formulation} and {Experimental} {Validation}}, volume = {7}, issn = {1553-7358}, shorttitle = {Simulation of the {Undiseased} {Human} {Cardiac} {Ventricular} {Action} {Potential}}, url = {http://journals.plos.org/ploscompbiol/article?id=10.1371/journal.pcbi.1002061}, doi = {10.1371/journal.pcbi.1002061}, abstract = {Author Summary Understanding and preventing irregular heart rhythms that can lead to sudden death begins with basic research regarding single cell electrical behavior. Most of these studies are performed using non-human cells. However, differences between human and non-human cell properties affect experimental results and invoke different mechanisms of responses to heart rate changes and to drugs. Using essential and previously unavailable experimental data from human hearts, we developed and validated an accurate mathematical model of the human cardiac cell. We compared cellular behaviors and mechanisms to an extensive dataset including measurements from more than 100 undiseased human hearts. The model responds to pacing rate and premature beats as in experiments. At very fast pacing rates, beat to beat alternations in intracellular calcium concentration and electrophysiological behavior were observed as in human heart experiments. In presence of drug block, arrhythmic behavior was observed. The basis for these and other important rhythmic and irregular rhythm behaviors was investigated using the model.}, number = {5}, urldate = {2017-09-05}, journal = {PLOS Computational Biology}, author = {O'Hara, Thomas and Virág, László and Varró, András and Rudy, Yoram}, month = may, year = {2011}, keywords = {arrhythmia, Behavior, Cardiac ventricles, Electrophysiology, Heart, Muscle cells, Rectifiers, Simulation and modeling}, pages = {e1002061}, file = {O'Hara et al (2011) - Simulation of the Undiseased Human Cardiac Ventricular Action Potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2WKM3WNV\\O'Hara et al (2011) - Simulation of the Undiseased Human Cardiac Ventricular Action Potential.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SWR9CMV3\\article.html:text/html} } @article{difrancesco_model_1985, title = {A model of cardiac electrical activity incorporating ionic pumps and concentration changes}, volume = {307}, url = {http://rstb.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/royptb/307/1133/353.full.pdf}, number = {1133}, journal = {Philosophical Transactions of the Royal Society of London B: Biological Sciences}, author = {DiFrancesco, D. and Noble, Denis}, year = {1985}, pages = {353--398}, file = {DiFrancesco and Noble - 1985 - A model of cardiac electrical activity incorporati.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\6AXS5XPZ\\DiFrancesco and Noble - 1985 - A model of cardiac electrical activity incorporati.pdf:application/pdf} } @article{varghese_conservation_1997, title = {A {Conservation} {Principle} and its {Effect} on the {Formulation} of {Na}–{Ca} {Exchanger} {Current} in {Cardiac} {Cells}}, volume = {189}, issn = {0022-5193}, url = {http://www.sciencedirect.com/science/article/pii/S0022519397904872}, doi = {10.1006/jtbi.1997.0487}, abstract = {In this paper we show the presence of a latent conservation principle in the formulation of ionic currents in cardiac cells and examine its effect on a formulation of the sodium–calcium exchange current appearing in the Noble model of the sinoatrial node cell in the mammalian heart [see Nobleet al. (1989) or Winslowet al. (1991)]. Our objective is to show that this formulation, if not corrected, will result in a serious instability in this cardiac cell model. In particular, under certain initial conditions, the solutions of the model equations will blow-up in finite time. We also propose a correction to the model equation of the sodium–calcium exchange current, and we show that the modified model agrees favorably with the original model. These phenomena also occur in the other cardiac cell models, such as those modeling the Purkinje fiber, the atrial cell and the ventricular cell. The changes proposed in this paper can be applied directly to these models as well.}, number = {1}, journal = {Journal of Theoretical Biology}, author = {Varghese, Anthony and Sell, George R.}, month = nov, year = {1997}, pages = {33--40}, file = {ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\NCBVAZCX\\S0022519397904872.html:text/html;Varghese_Sell (1997) - A Conservation Principle and its Effect on the Formulation of Na–Ca Exchanger.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\VTRJ73QJ\\Varghese_Sell (1997) - A Conservation Principle and its Effect on the Formulation of Na–Ca Exchanger.pdf:application/pdf} } @article{luo_dynamic_1994-1, title = {A dynamic model of the cardiac ventricular action potential. {II}. {Afterdepolarizations}, triggered activity, and potentiation.}, volume = {74}, copyright = {Copyright © 1994 by American Heart Association}, issn = {0009-7330, 1524-4571}, url = {http://circres.ahajournals.org.ezp.lib.unimelb.edu.au/content/74/6/1097}, doi = {10.1161/01.RES.74.6.1097}, abstract = {The action potential model presented in our accompanying article in this journal is used to investigate phenomena that involve dynamic changes of [Ca2+]i, as described below. Delayed afterdepolarizations (DADs) are induced by spontaneous Ca2+ release from the sarcoplasmic reticulum (SR), which, in turn, activates both the Na(+)-Ca2+ exchanger (INaCa) and a nonspecific Ca(2+)-activated current (Ins(Ca)). The relative contributions of INaCa and of Ins(Ca) to the generation of DADs are different under different degrees of Ca2+ overload. Early afterdepolarizations (EADs) can be categorized into two types: (1) plateau EADs, resulting from a secondary activation of the L-type Ca2+ current during the plateau of an action potential, and (2) phase-3 EADs, resulting from activation of INaCa and Ins(Ca) by increased [Ca2+]i due to spontaneous Ca2+ release from the SR during the late repolarization phase. Spontaneous rhythmic activity and triggered activity are caused by spontaneous Ca2+ release from the SR under conditions of Ca2+ overload. Postextrasystolic potentiation reflects the time delay associated with translocation of Ca2+ from network SR to junctional SR. The cell is paced at high frequencies to investigate the long-term effects on the intracellular ionic concentrations.}, language = {en}, number = {6}, urldate = {2017-09-05}, journal = {Circulation Research}, author = {Luo, C. H. and Rudy, Y.}, month = jun, year = {1994}, pmid = {7514510}, pages = {1097--1113}, file = {Luo_Rudy (1994) - A dynamic model of the cardiac ventricular action potential.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\P2CPQNAI\\Luo_Rudy (1994) - A dynamic model of the cardiac ventricular action potential.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\2EGNCTKG\\1097.html:text/html} } @article{mullins_mechanism_1977, title = {A mechanism for {Na}/{Ca} transport.}, volume = {70}, copyright = {© 1977 Rockefeller University Press}, issn = {0022-1295, 1540-7748}, url = {http://jgp.rupress.org.ezp.lib.unimelb.edu.au/content/70/6/681}, doi = {10.1085/jgp.70.6.681}, abstract = {{\textless}p{\textgreater}A model is developed which requires the binding of 4 Na+ to a carrier before a Ca binding site is induced on the opposite side of the membrane. Upon binding Ca, this carrier translocates Na and Ca. The existence of partially Na-loaded but nonmobile forms for the carrier (NaX, Na2X, Na3X) suffices to explain both the activating and the inhibitory effects of Na on the Ca transport reaction. Analytical expressions for Ca efflux and influx in terms of [Na]o, [Na]i, [Ca]o, [Ca]i, and Em are developed for the Na/Ca exchange system at equilibrium; these provide for a quantitative description of Ca fluxes. Under nonequilibrium conditions, appropriate modifications of the flux equations can be developed. These show a dependence of Ca efflux on [Ca]o and of Ca influx on [Ca]i. The large effect of internal ATP on Ca efflux and influx in squid axons, with no change in net Ca flux, can be understood on the single assumption that ATP changes the affinity of the carrier for Na at both faces of the membrane without providing an energy input to the transport reaction.{\textless}/p{\textgreater}}, language = {en}, number = {6}, urldate = {2017-09-05}, journal = {The Journal of General Physiology}, author = {Mullins, L. J.}, month = dec, year = {1977}, pmid = {591918}, pages = {681--695}, file = {Mullins (1977) - A mechanism for Na-Ca transport.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\IVUFAQI7\\Mullins (1977) - A mechanism for Na-Ca transport.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\W8DV8WTM\\tab-pdf.html:text/html} } @article{ederer_thermodynamically_2007, title = {Thermodynamically {Feasible} {Kinetic} {Models} of {Reaction} {Networks}}, volume = {92}, issn = {0006-3495}, url = {http://www.sciencedirect.com/science/article/pii/S0006349507709943}, doi = {10.1529/biophysj.106.094094}, abstract = {The dynamics of biological reaction networks are strongly constrained by thermodynamics. An holistic understanding of their behavior and regulation requires mathematical models that observe these constraints. However, kinetic models may easily violate the constraints imposed by the principle of detailed balance, if no special care is taken. Detailed balance demands that in thermodynamic equilibrium all fluxes vanish. We introduce a thermodynamic-kinetic modeling (TKM) formalism that adapts the concepts of potentials and forces from irreversible thermodynamics to kinetic modeling. In the proposed formalism, the thermokinetic potential of a compound is proportional to its concentration. The proportionality factor is a compound-specific parameter called capacity. The thermokinetic force of a reaction is a function of the potentials. Every reaction has a resistance that is the ratio of thermokinetic force and reaction rate. For mass-action type kinetics, the resistances are constant. Since it relies on the thermodynamic concept of potentials and forces, the TKM formalism structurally observes detailed balance for all values of capacities and resistances. Thus, it provides an easy way to formulate physically feasible, kinetic models of biological reaction networks. The TKM formalism is useful for modeling large biological networks that are subject to many detailed balance relations.}, number = {6}, journal = {Biophysical Journal}, author = {Ederer, Michael and Gilles, Ernst Dieter}, month = mar, year = {2007}, pages = {1846--1857}, file = {Ederer_Gilles (2007) - Thermodynamically Feasible Kinetic Models of Reaction Networks.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\WBV393TP\\Ederer_Gilles (2007) - Thermodynamically Feasible Kinetic Models of Reaction Networks.pdf:application/pdf;ScienceDirect Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\ZADV4JKU\\S0006349507709943.html:text/html} } @incollection{gawthrop_bond-graph_2017, title = {Bond-{Graph} {Modelling} and {Causal} {Analysis} of {Biomolecular} {Systems}}, isbn = {978-3-319-47433-5 978-3-319-47434-2}, url = {https://link-springer-com.ezp.lib.unimelb.edu.au/chapter/10.1007/978-3-319-47434-2_16}, abstract = {Bond graph modelling of the biomolecular systems of living organisms is introduced. Molecular species are represented by non-linear C components and reactions by non-linear two-port R components. As living systems are neither at thermodynamic equilibrium nor closed, open and non-equilibrium systems are considered and illustrated using examples of biomolecular systems. Open systems are modelled using chemostats: chemical species with fixed concentration. In addition to their role in ensuring that models are energetically correct, bond graphs provide a powerful and natural way of representing and analysing causality. Causality is used in this chapter to examine the properties of the junction structures of biomolecular systems and how they relate to biomolecular concepts.}, language = {en}, urldate = {2017-09-06}, booktitle = {Bond {Graphs} for {Modelling}, {Control} and {Fault} {Diagnosis} of {Engineering} {Systems}}, publisher = {Springer, Cham}, author = {Gawthrop, Peter J.}, year = {2017}, note = {DOI: 10.1007/978-3-319-47434-2\_16}, pages = {587--623}, file = {Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\SGWJ5AWE\\978-3-319-47434-2_16.html:text/html} } @article{gawthrop_energy-based_2017, title = {Energy-based analysis of biomolecular pathways}, volume = {473}, copyright = {© 2017 The Author(s). http://royalsocietypublishing.org.ezp.lib.unimelb.edu.au/licencePublished by the Royal Society. All rights reserved.}, issn = {1364-5021, 1471-2946}, url = {http://rspa.royalsocietypublishing.org.ezp.lib.unimelb.edu.au/content/473/2202/20160825}, doi = {10.1098/rspa.2016.0825}, abstract = {Decomposition of biomolecular reaction networks into pathways is a powerful approach to the analysis of metabolic and signalling networks. Current approaches based on analysis of the stoichiometric matrix reveal information about steady-state mass flows (reaction rates) through the network. In this work, we show how pathway analysis of biomolecular networks can be extended using an energy-based approach to provide information about energy flows through the network. This energy-based approach is developed using the engineering-inspired bond graph methodology to represent biomolecular reaction networks. The approach is introduced using glycolysis as an exemplar; and is then applied to analyse the efficiency of free energy transduction in a biomolecular cycle model of a transporter protein [sodium-glucose transport protein 1 (SGLT1)]. The overall aim of our work is to present a framework for modelling and analysis of biomolecular reactions and processes which considers energy flows and losses as well as mass transport.}, language = {en}, number = {2202}, urldate = {2017-09-06}, journal = {Proc. R. Soc. A}, author = {Gawthrop, Peter J. and Crampin, Edmund J.}, month = jun, year = {2017}, pages = {20160825}, file = {Gawthrop_Crampin (2017) - Energy-based analysis of biomolecular pathways.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\EFH5FPF3\\Gawthrop_Crampin (2017) - Energy-based analysis of biomolecular pathways.pdf:application/pdf;Snapshot:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\JCJ2XH7N\\20160825.html:text/html} } @phdthesis{terkildsen_modelling_2006, type = {Masters {Thesis}}, title = {Modelling {Extracellular} {Potassium} {Accumulation} in {Cardiac} {Ischaemia}}, school = {The University of Auckland}, author = {Terkildsen, Jonna}, year = {2006} } @article{oster_network_1971, title = {Network thermodynamics}, volume = {234}, url = {http://160592857366.free.fr/joe/ebooks/ShareData/NetworkThermo.pdf}, number = {5329}, urldate = {2017-09-28}, journal = {Nature}, author = {Oster, George and Perelson, Alan and Katchalsky, Aharon}, year = {1971}, pages = {393--399}, file = {NetworkThermo.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\KAJT67XU\\NetworkThermo.pdf:application/pdf} } @inproceedings{kennedy_particle_1995, title = {Particle swarm optimization}, volume = {4}, abstract = {A concept for the optimization of nonlinear functions using particle swarm methodology is introduced. The evolution of several paradigms is outlined, and an implementation of one of the paradigms is discussed. Benchmark testing of the paradigm is described, and applications, including nonlinear function optimization and neural network training, are proposed. The relationships between particle swarm optimization and both artificial life and genetic algorithms are described}, booktitle = {{IEEE} {International} {Conference} on {Neural} {Networks}, 1995. {Proceedings}}, author = {Kennedy, J. and Eberhart, R.}, month = nov, year = {1995}, keywords = {artificial intelligence, artificial life, Artificial neural networks, Birds, Educational institutions, evolution, genetic algorithms, Humans, Marine animals, multidimensional search, neural nets, neural network, nonlinear functions, optimization, Optimization methods, particle swarm, Particle swarm optimization, Performance evaluation, search problems, simulation, social metaphor, Testing}, pages = {1942--1948 vol.4}, file = {IEEE Xplore Abstract Record:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\RB8TSSUR\\488968.html:text/html;Kennedy_Eberhart (1995) - Particle swarm optimization.pdf:C\:\\Users\\panm\\AppData\\Roaming\\Mozilla\\Firefox\\Profiles\\eexbckdj.default\\zotero\\storage\\R8IIXBVG\\Kennedy_Eberhart (1995) - Particle swarm optimization.pdf:application/pdf} }