- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-07-09 07:36:31+12:00
- Desc:
- committing version01 of thomsen_neubig_1989
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/thomsen_neubig_1989/rawfile/851326f149c4230e68ad4739ddc04c52cb8e409d/thomsen_neubig_1989.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : G_protein_activation_1989.xml
CREATED : 14th November 2001
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
Department of Engineering Science
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of a G-protein activation
pathway, based on the mathematical model of Thomsen and Neubig (1989).
CHANGES :
21/01/2002 - AAC - Updated metadata to conform to the 16/1/02 CellML Metadata
1.0 Specification.
22/07/2002 - CML - Added more metadata.
09/04/2003 - AAC - Added publication date information.
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:pathway_editor="http://www.physiome.com/pathway_editor/1.0#" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" pathway_editor:rendering_config_file="G protein activation pathway 1989render.xml" cmeta:id="thomsen_neubig_1989_version01" name="thomsen_neubig_1989_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Model Of G-Protein Activation</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
G-proteins, or guanine nucleotide-binding proteins, serve to couple receptors to membrane-bound enzymes such as adenylate cyclase. In turn this induces the generation of secondary messengers such as cAMP for purposes of signal transduction. The inactive form of the G-protein consists of alpha, beta, and gamma subunits with a molecule of GDP bound to the alpha subunit. When a ligand-bound receptor interacts with the G-protein, it catalyses the exchange of GDP for GTP and activates the G-protein. The G-protein is then released from the receptor and it dissociates into separate beta-gamma and alpha-GTP (active) subunits. Active G-proteins are returned to their inactive state upon the hydrolysis of GTP to GDP by the intrinsic GTPase activity of the alpha-subunit and the alpha-GDP and beta-gamma subunits can recombine. (See <xref linkend="fig_pathway_diagram"/> below).
</para>
<para>
This description of a general G-protein activation pathway is based on the mathematical model described by W.J Thomsen and R.R. Neubig in their 1989 paper. The model does not include the steps of dissociation and recombination of the alpha and beta-gamma subunits of the G-protein. In addition, it is assumed that the number of membrane bound receptors (Rt) is constant.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
Rapid kinetics of alpha 2-adrenergic inhibition of adenylate cyclase. Evidence for a distal rate-limiting step, W.J. Thomsen and R.R. Neubig, 1989, <ulink url="http://pubs.acs.org/journals/bichaw/">
<emphasis>Biochemistry</emphasis>
</ulink>, 28, 8778-8786. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=2574993&dopt=Abstract">PubMed ID: 2574993</ulink>
</para>
<para>
The raw CellML description of the G-protein activation pathway model can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>. For an example of a more complete documentation of another real reaction pathway, see <ulink url="${HTML_EXMPL_BI_EGF_INTRO}">The Bhalla Iyengar EGF Pathway Model, 1999</ulink>.
</para>
<informalfigure float="0" id="fig_pathway_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>the conventional rendering of a G-protein activation pathway</title>
</objectinfo>
<imagedata fileref="conventional_rendering.gif"/>
</imageobject>
</mediaobject>
<caption>A rendering of a G-protein activation pathway. Species are represented by rounded rectangles, and reactions by arrows.</caption>
</informalfigure>
<para>
In CellML, models are thought of as connected networks of discrete components. These components may correspond to physiologically separated regions or chemically distinct objects, or may be useful modelling abstractions. This pathway model has 17 components representing chemically distinct objects (11 chemical species and six reactions) and one component for modelling convenience in which global variables such as time are declared. The CellML rendering of the G-protein activation pathway model is shown in <xref linkend="fig_cellml_rendering"/> (the different shapes in the diagram are explained in the <ulink url="${HTML_EXMPL_GRAPHICAL_NOTATION}">notation guide</ulink>). The action of a catalyst on a reaction is again represented by dashed lines.
</para>
<informalfigure float="0" id="fig_cellml_rendering">
<mediaobject>
<imageobject>
<objectinfo>
<title>the cellml rendering of a G-protein activation pathway</title>
</objectinfo>
<imagedata fileref="cellml_rendering.gif"/>
</imageobject>
</mediaobject>
<caption>The CellML rendering of a G-protein activation pathway.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!--
We start the model definition with a definition of some named
sets of units for use throughout the model.
-->
<units name="molar">
<unit units="mole"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="molar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant_units">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant_units">
<unit units="molar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<component name="global_variables">
<variable units="second" public_interface="out" name="time"/>
</component>
<component cmeta:id="Pi" name="Pi">
<variable units="molar" public_interface="out" name="Pi"/>
<variable units="flux" public_interface="in" name="delta_Pi_rxn5"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Pi</ci>
</apply>
<ci>delta_Pi_rxn5</ci>
</apply>
</math>
</component>
<component cmeta:id="L" name="L">
<variable units="molar" public_interface="out" name="L" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_L_rxn0"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>L</ci>
</apply>
<ci>delta_L_rxn0</ci>
</apply>
</math>
</component>
<component cmeta:id="R" name="R">
<variable units="molar" public_interface="out" name="R" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_R_rxn0"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>R</ci>
</apply>
<ci>delta_R_rxn0</ci>
</apply>
</math>
</component>
<component cmeta:id="C" name="C">
<variable units="molar" public_interface="out" name="C"/>
<variable units="flux" public_interface="in" name="delta_C_rxn0"/>
<variable units="flux" public_interface="in" name="delta_C_rxn4"/>
<variable units="flux" public_interface="in" name="delta_C_rxn1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C</ci>
</apply>
<apply>
<plus/>
<ci>delta_C_rxn0</ci>
<ci>delta_C_rxn4</ci>
<ci>delta_C_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="G_GDP" name="G_GDP">
<variable units="molar" public_interface="out" name="G_GDP"/>
<variable units="flux" public_interface="in" name="delta_G_GDP_rxn5"/>
<variable units="flux" public_interface="in" name="delta_G_GDP_rxn1"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>G_GDP</ci>
</apply>
<apply>
<plus/>
<ci>delta_G_GDP_rxn5</ci>
<ci>delta_G_GDP_rxn1</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="C_G_GDP" name="C_G_GDP">
<variable units="molar" public_interface="out" name="C_G_GDP"/>
<variable units="flux" public_interface="in" name="delta_C_G_GDP_rxn1"/>
<variable units="flux" public_interface="in" name="delta_C_G_GDP_rxn2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_G_GDP</ci>
</apply>
<apply>
<plus/>
<ci>delta_C_G_GDP_rxn1</ci>
<ci>delta_C_G_GDP_rxn2</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="GDP" name="GDP">
<variable units="molar" public_interface="out" name="GDP"/>
<variable units="flux" public_interface="in" name="delta_GDP_rxn2"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>GDP</ci>
</apply>
<ci>delta_GDP_rxn2</ci>
</apply>
</math>
</component>
<component cmeta:id="C_G" name="C_G">
<variable units="molar" public_interface="out" name="C_G"/>
<variable units="flux" public_interface="in" name="delta_C_G_rxn2"/>
<variable units="flux" public_interface="in" name="delta_C_G_rxn3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_G</ci>
</apply>
<apply>
<plus/>
<ci>delta_C_G_rxn2</ci>
<ci>delta_C_G_rxn3</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="GTP" name="GTP">
<variable units="molar" public_interface="out" name="GTP" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_GTP_rxn3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>GTP</ci>
</apply>
<ci>delta_GTP_rxn3</ci>
</apply>
</math>
</component>
<component cmeta:id="C_G_GTP" name="C_G_GTP">
<variable units="molar" public_interface="out" name="C_G_GTP"/>
<variable units="flux" public_interface="in" name="delta_C_G_GTP_rxn3"/>
<variable units="flux" public_interface="in" name="delta_C_G_GTP_rxn4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>C_G_GTP</ci>
</apply>
<apply>
<plus/>
<ci>delta_C_G_GTP_rxn3</ci>
<ci>delta_C_G_GTP_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="G__GTP" name="G__GTP">
<variable units="molar" public_interface="out" name="G__GTP"/>
<variable units="flux" public_interface="in" name="delta_G__GTP_rxn4"/>
<variable units="flux" public_interface="in" name="delta_G__GTP_rxn5"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>G__GTP</ci>
</apply>
<apply>
<plus/>
<ci>delta_G__GTP_rxn4</ci>
<ci>delta_G__GTP_rxn5</ci>
</apply>
</apply>
</math>
</component>
<component name="reaction0">
<variable units="molar" public_interface="in" name="R"/>
<variable units="molar" public_interface="in" name="L"/>
<variable units="molar" public_interface="in" name="C"/>
<variable units="flux" public_interface="out" name="delta_R_rxn0"/>
<variable units="flux" public_interface="out" name="delta_L_rxn0"/>
<variable units="flux" public_interface="out" name="delta_C_rxn0"/>
<variable units="second_order_rate_constant_units" name="k0" initial_value="5000000.0"/>
<variable units="first_order_rate_constant_units" name="k0_" initial_value="0.5"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="R">
<role stoichiometry="1" direction="forward" delta_variable="delta_R_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="L">
<role stoichiometry="1" direction="forward" delta_variable="delta_L_rxn0" role="reactant"/>
</variable_ref>
<variable_ref variable="C">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_rxn0" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k0</ci>
<ci>R</ci>
<ci>L</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k0_</ci>
<ci>C</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction1">
<variable units="molar" public_interface="in" name="G_GDP"/>
<variable units="molar" public_interface="in" name="C"/>
<variable units="molar" public_interface="in" name="C_G_GDP"/>
<variable units="flux" public_interface="out" name="delta_G_GDP_rxn1"/>
<variable units="flux" public_interface="out" name="delta_C_rxn1"/>
<variable units="flux" public_interface="out" name="delta_C_G_GDP_rxn1"/>
<variable units="second_order_rate_constant_units" name="k1" initial_value="0.1"/>
<variable units="first_order_rate_constant_units" name="k1_" initial_value="0.1"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="G_GDP">
<role stoichiometry="1" direction="forward" delta_variable="delta_G_GDP_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="C">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="C_G_GDP">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_G_GDP_rxn1" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k1</ci>
<ci>G_GDP</ci>
<ci>C</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k1_</ci>
<ci>C_G_GDP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction2">
<variable units="molar" public_interface="in" name="C_G_GDP"/>
<variable units="molar" public_interface="in" name="GDP"/>
<variable units="molar" public_interface="in" name="C_G"/>
<variable units="flux" public_interface="out" name="delta_C_G_GDP_rxn2"/>
<variable units="flux" public_interface="out" name="delta_GDP_rxn2"/>
<variable units="flux" public_interface="out" name="delta_C_G_rxn2"/>
<variable units="first_order_rate_constant_units" name="k2" initial_value="5.0"/>
<variable units="second_order_rate_constant_units" name="k2_" initial_value="0.0001"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="C_G_GDP">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_G_GDP_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="GDP">
<role stoichiometry="1" direction="forward" delta_variable="delta_GDP_rxn2" role="product"/>
</variable_ref>
<variable_ref variable="C_G">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_G_rxn2" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>C_G_GDP</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>GDP</ci>
<ci>C_G</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="molar" public_interface="in" name="GTP"/>
<variable units="molar" public_interface="in" name="C_G"/>
<variable units="molar" public_interface="in" name="C_G_GTP"/>
<variable units="flux" public_interface="out" name="delta_GTP_rxn3"/>
<variable units="flux" public_interface="out" name="delta_C_G_rxn3"/>
<variable units="flux" public_interface="out" name="delta_C_G_GTP_rxn3"/>
<variable units="second_order_rate_constant_units" name="k3" initial_value="5000000.0"/>
<variable units="first_order_rate_constant_units" name="k3_" initial_value="1.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="GTP">
<role stoichiometry="1" direction="forward" delta_variable="delta_GTP_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="C_G">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_G_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="C_G_GTP">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_G_GTP_rxn3" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k3</ci>
<ci>GTP</ci>
<ci>C_G</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k3_</ci>
<ci>C_G_GTP</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction4">
<variable units="molar" public_interface="in" name="C_G_GTP"/>
<variable units="molar" public_interface="in" name="G__GTP"/>
<variable units="molar" public_interface="in" name="C"/>
<variable units="flux" public_interface="out" name="delta_C_G_GTP_rxn4"/>
<variable units="flux" public_interface="out" name="delta_G__GTP_rxn4"/>
<variable units="flux" public_interface="out" name="delta_C_rxn4"/>
<variable units="first_order_rate_constant_units" name="k4" initial_value="0.1"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="C_G_GTP">
<role stoichiometry="1" delta_variable="delta_C_G_GTP_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="G__GTP">
<role stoichiometry="1" delta_variable="delta_G__GTP_rxn4" role="product"/>
</variable_ref>
<variable_ref variable="C">
<role stoichiometry="1" delta_variable="delta_C_rxn4" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k4</ci>
<ci>C_G_GTP</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction5">
<variable units="molar" public_interface="in" name="G__GTP"/>
<variable units="molar" public_interface="in" name="Pi"/>
<variable units="molar" public_interface="in" name="G_GDP"/>
<variable units="flux" public_interface="out" name="delta_G__GTP_rxn5"/>
<variable units="flux" public_interface="out" name="delta_Pi_rxn5"/>
<variable units="flux" public_interface="out" name="delta_G_GDP_rxn5"/>
<variable units="first_order_rate_constant_units" name="k5" initial_value="2.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="G__GTP">
<role stoichiometry="1" delta_variable="delta_G__GTP_rxn5" role="reactant"/>
</variable_ref>
<variable_ref variable="Pi">
<role stoichiometry="1" delta_variable="delta_Pi_rxn5" role="product"/>
</variable_ref>
<variable_ref variable="G_GDP">
<role stoichiometry="1" delta_variable="delta_G_GDP_rxn5" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k5</ci>
<ci>G__GTP</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="reaction5" component_1="Pi"/>
<map_variables variable_2="Pi" variable_1="Pi"/>
<map_variables variable_2="delta_Pi_rxn5" variable_1="delta_Pi_rxn5"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="L"/>
<map_variables variable_2="L" variable_1="L"/>
<map_variables variable_2="delta_L_rxn0" variable_1="delta_L_rxn0"/>
</connection>
<connection>
<map_components component_2="reaction0" component_1="R"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="delta_R_rxn0" variable_1="delta_R_rxn0"/>
</connection>
<connection>
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<connection>
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<connection>
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Rapid kinetics of alpha 2-adrenergic inhibition of adenylate cyclase. Evidence for a distal rate-limiting step
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Updated metadata to conform to the 16/1/02 CellML Metadata 1.0
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The University of Auckland, Bioengineering Research Group
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