- Author:
- Mathieu Deneux <mathieu.deneux@gmail.com>
- Date:
- 2016-08-01 11:06:11+12:00
- Desc:
- Added a SEDML file
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/36d/rawfile/7d6624ef983720ec2234013821ec45e7def7492d/ciliberto_petrus_tyson_sible_2003.cellml
<?xml version="1.0"?>
<!--
This CellML file was generated on 16/12/2008 at 9:19:52 at a.m. using:
COR (0.9.31.1125)
Copyright 2002-2008 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk
CellML 1.0 was used to generate this model
http://www.CellML.org/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" cmeta:id="ciliberto_2003" name="ciliberto_2003">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Kinetic Model of the Cyclin E/Cdk2 Developmental Timer in Xenopus laevis embryos</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML version of the model has been checked in OpenCell and the model runs to replicate the results in the original published paper. This model uses the initial conditions that recreate the results in figure 6. The model runs in COR but the duration of the model simulation is too long for the results to be properly displayed in COR. The units have been checked and they are consistent.</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: Early cell cycles of Xenopus laevis embryos are characterized by rapid oscillations in the activity of two cyclin-dependent kinases. Cdk1 activity peaks at mitosis, driven by periodic degradation of cyclins A and B. In contrast, Cdk2 activity oscillates twice per cell cycle, despite a constant level of its partner, cyclin E. Cyclin E degrades at a fixed time after fertilization, normally corresponding to the midblastula transition. Based on published data and new experiments, we constructed a mathematical model in which: (1) oscillations in Cdk2 activity depend upon changes in phosphorylation, (2) Cdk2 participates in a negative feedback loop with the inhibitory kinase Wee1; (3) cyclin E is cooperatively removed from the oscillatory system; and (4) removed cyclin E is degraded by a pathway activated by cyclin E/Cdk2 itself. The model's predictions about embryos injected with Xic1, a stoichiometric inhibitor of cyclin E/Cdk2, were experimentally validated.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
A kinetic model of the cyclin E/Cdk2 developmental timer in <emphasis>Xenopus laevis</emphasis> embryos, Andrea Ciliberto, Matthew J. Petrus, John J. Tyson, and Jill C. Sible, 2003,
<emphasis>Biophysical Chemistry</emphasis>
, 104, 573-589. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/12914904">PubMed ID: 12914904</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>reaction diagram</title>
</objectinfo>
<imagedata fileref="ciliberto_2003.png"/>
</imageobject>
</mediaobject>
<caption>A theoretical molecular mechanism of the cyclin E/Cdk2 developmental timer was used to construct the mathematical model. The dashed box represents a mechanism for removing cyclin E/Cdk2 from the oscillatory subsystem, which is activated by the "removed" form of cyclin E/Cdk2. The removal step is cooperative in that the more cyclin E/Cdk2 there is bound to the dashed box, the faster is the association reaction. A kinase (Kin) is introduced between cyclin E/Cdk2 and Wee1 to create a time lag in the negative feedback loop.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<units name="minute">
<unit multiplier="60" units="second"/>
</units>
<units name="first_order_rate_constant">
<unit exponent="-1" units="minute"/>
</units>
<component name="environment">
<variable cmeta:id="environment_time" name="time" public_interface="out" units="minute"/>
</component>
<component name="Cdk2_CycE">
<variable cmeta:id="Cdk2_CycE_Cdk2_CycE" initial_value="0.06" name="Cdk2_CycE" public_interface="out" units="dimensionless"/>
<variable name="kwee" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="k25A" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Wee1_a" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>k25A</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>Cdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCdk2_CycE">
<variable cmeta:id="PCdk2_CycE_PCdk2_CycE" initial_value="0.94" name="PCdk2_CycE" public_interface="out" units="dimensionless"/>
<variable name="kwee" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="k25A" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Wee1_a" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>k25A</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Wee1_a">
<variable cmeta:id="Wee1_a_Wee1_a" initial_value="1.02" name="Wee1_a" public_interface="out" units="dimensionless"/>
<variable initial_value="0.01" name="Jwact" units="dimensionless"/>
<variable initial_value="0.01" name="Jwinact" units="dimensionless"/>
<variable initial_value="8" name="Wee1_total" units="dimensionless"/>
<variable initial_value="0.75" name="kwact" units="first_order_rate_constant"/>
<variable initial_value="1.5" name="kwinact" units="first_order_rate_constant"/>
<variable name="Kin_a" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Wee1_a</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kwact</ci>
<apply>
<minus/>
<ci>Wee1_total</ci>
<ci>Wee1_a</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Jwact</ci>
<ci>Wee1_total</ci>
</apply>
<ci>Wee1_a</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kwinact</ci>
<ci>Kin_a</ci>
<ci>Wee1_a</ci>
</apply>
<apply>
<plus/>
<ci>Jwinact</ci>
<ci>Wee1_a</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Kin_a">
<variable cmeta:id="Kin_a_Kin_a" initial_value="0.6" name="Kin_a" public_interface="out" units="dimensionless"/>
<variable initial_value="0.01" name="Jiact" units="dimensionless"/>
<variable initial_value="0.01" name="Jiinact" units="dimensionless"/>
<variable initial_value="0.15" name="kiact" units="first_order_rate_constant"/>
<variable initial_value="0.6" name="kiinact" units="first_order_rate_constant"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Kin_a</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kiact</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Kin_a</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Jiact</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</apply>
<ci>Kin_a</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kiinact</ci>
<ci>Cdk2_CycE</ci>
<ci>Kin_a</ci>
</apply>
<apply>
<plus/>
<ci>Jiinact</ci>
<ci>Kin_a</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cdk2_CycErem">
<variable cmeta:id="Cdk2_CycErem_Cdk2_CycErem" initial_value="0" name="Cdk2_CycErem" public_interface="out" units="dimensionless"/>
<variable name="kedeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="kxdeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Deg_a" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>koff</ci>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>Cdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PCdk2_CycErem">
<variable initial_value="0" name="PCdk2_CycErem" public_interface="out" units="dimensionless"/>
<variable name="kedeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="kxdeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Deg_a" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>koff</ci>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Deg_a">
<variable cmeta:id="Deg_a_Deg_a" initial_value="0" name="Deg_a" public_interface="out" units="dimensionless"/>
<variable name="Heav" units="dimensionless"/>
<variable initial_value="0.023" name="kdact" units="first_order_rate_constant"/>
<variable initial_value="0.3" name="theta" units="dimensionless"/>
<variable name="x" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Deg_a</ci>
</apply>
<apply>
<times/>
<ci>kdact</ci>
<ci>Heav</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>x</ci>
<apply>
<minus/>
<ci>Cdk2_CycErem</ci>
<ci>theta</ci>
</apply>
</apply>
<apply>
<eq/>
<ci>Heav</ci>
<piecewise>
<piece>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<ci>x</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="Xic">
<variable initial_value="3" name="Xic" public_interface="out" units="dimensionless"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>kdissoc</ci>
<apply>
<plus/>
<ci>Xic_Cdk2_CycE</ci>
<ci>Xic_PCdk2_CycE</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<apply>
<plus/>
<ci>Cdk2_CycE</ci>
<ci>PCdk2_CycE</ci>
<ci>Cdk2_CycErem</ci>
<ci>PCdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_Cdk2_CycE">
<variable initial_value="0" name="Xic_Cdk2_CycE" public_interface="out" units="dimensionless"/>
<variable name="kwee" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="k25A" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Wee1_a" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_Cdk2_CycE</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>k25A</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_PCdk2_CycE">
<variable initial_value="0" name="Xic_PCdk2_CycE" public_interface="out" units="dimensionless"/>
<variable name="kwee" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="k25A" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Wee1_a" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kwee</ci>
<ci>Wee1_a</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
<apply>
<times/>
<ci>k25A</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_Cdk2_CycErem">
<variable initial_value="0" name="Xic_Cdk2_CycErem" public_interface="out" units="dimensionless"/>
<variable name="kedeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="kxdeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Deg_a" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_Cdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xic_PCdk2_CycErem">
<variable initial_value="0" name="Xic_PCdk2_CycErem" public_interface="out" units="dimensionless"/>
<variable name="kedeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="kon" public_interface="in" units="first_order_rate_constant"/>
<variable name="kxdeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="koff" public_interface="in" units="first_order_rate_constant"/>
<variable name="kassoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="kdissoc" public_interface="in" units="first_order_rate_constant"/>
<variable name="phi" public_interface="in" units="dimensionless"/>
<variable name="Deg" public_interface="in" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kassoc</ci>
<ci>Xic</ci>
<ci>PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kon</ci>
<ci>phi</ci>
<ci>Xic_PCdk2_CycE</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci>kdissoc</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>koff</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Xicrem">
<variable initial_value="0" name="Xicrem" public_interface="out" units="dimensionless"/>
<variable name="kedeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="kxdeg" public_interface="in" units="first_order_rate_constant"/>
<variable name="Deg_a" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Xicrem</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_Cdk2_CycErem</ci>
</apply>
<apply>
<times/>
<ci>kedeg</ci>
<ci>Deg_a</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
<apply>
<times/>
<ci>kxdeg</ci>
<ci>Xicrem</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cyc_total">
<variable name="Cyc_total" public_interface="out" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Cyc_total</ci>
<apply>
<plus/>
<ci>Xic_PCdk2_CycE</ci>
<ci>Xic_Cdk2_CycE</ci>
<ci>Xic_PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>PCdk2_CycErem</ci>
<ci>Cdk2_CycErem</ci>
<ci>Cdk2_CycE</ci>
<ci>PCdk2_CycE</ci>
</apply>
</apply>
</math>
</component>
<component name="Xic_total">
<variable name="Xic_total" public_interface="out" units="dimensionless"/>
<variable name="Xic" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycE" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xicrem" public_interface="in" units="dimensionless"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Xic_total</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>Xic</ci>
<ci>Xic_PCdk2_CycE</ci>
<ci>Xic_Cdk2_CycE</ci>
<ci>Xic_PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>Xicrem</ci>
</apply>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">3</cn>
</apply>
</apply>
</math>
</component>
<component name="kinetic_parameters">
<variable initial_value="1.5" name="kwee" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="k25A" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.02" name="kon" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.0001" name="koff" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.1" name="kassoc" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.001" name="kdissoc" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.017" name="kedeg" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="0.01" name="kxdeg" public_interface="out" units="first_order_rate_constant"/>
<variable name="phi" public_interface="out" units="dimensionless"/>
<variable initial_value="0" name="Deg" public_interface="out" units="dimensionless"/>
<variable initial_value="0.001" name="epsilon" units="dimensionless"/>
<variable name="pool" public_interface="out" units="dimensionless"/>
<variable initial_value="4" name="n" units="dimensionless"/>
<variable initial_value="0.4" name="L" units="dimensionless"/>
<variable name="Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_Cdk2_CycErem" public_interface="in" units="dimensionless"/>
<variable name="Xic_PCdk2_CycErem" public_interface="in" units="dimensionless"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>phi</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>epsilon</ci>
<apply>
<power/>
<ci>pool</ci>
<ci>n</ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<power/>
<ci>L</ci>
<ci>n</ci>
</apply>
<apply>
<power/>
<ci>pool</ci>
<ci>n</ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<eq/>
<ci>pool</ci>
<apply>
<plus/>
<ci>Cdk2_CycErem</ci>
<ci>PCdk2_CycErem</ci>
<ci>Xic_Cdk2_CycErem</ci>
<ci>Xic_PCdk2_CycErem</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="Cdk2_CycE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Wee1_a" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Kin_a" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycErem" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycErem" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Deg_a" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycErem" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycErem" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Xicrem" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="Wee1_a"/>
<map_variables variable_1="Wee1_a" variable_2="Wee1_a"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="PCdk2_CycE"/>
<map_variables variable_1="PCdk2_CycE" variable_2="PCdk2_CycE"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="Cdk2_CycErem"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="Xic"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="Wee1_a"/>
<map_variables variable_1="Wee1_a" variable_2="Wee1_a"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="PCdk2_CycErem"/>
<map_variables variable_1="PCdk2_CycErem" variable_2="PCdk2_CycErem"/>
<map_variables variable_1="PCdk2_CycE" variable_2="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="Xic"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
<map_variables variable_1="PCdk2_CycE" variable_2="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="PCdk2_CycE" variable_2="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Kin_a" component_2="Cdk2_CycE"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycErem" component_2="Xic"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycErem" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycErem" component_2="Xic"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
<map_variables variable_1="PCdk2_CycErem" variable_2="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycErem" component_2="Deg_a"/>
<map_variables variable_1="Deg_a" variable_2="Deg_a"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycErem" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="PCdk2_CycErem" variable_2="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Wee1_a" component_2="Kin_a"/>
<map_variables variable_1="Kin_a" variable_2="Kin_a"/>
</connection>
<connection>
<map_components component_1="Deg_a" component_2="Cdk2_CycErem"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
<map_variables variable_1="Deg_a" variable_2="Deg_a"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Cdk2_CycE"/>
<map_variables variable_1="Cdk2_CycE" variable_2="Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="PCdk2_CycE"/>
<map_variables variable_1="PCdk2_CycE" variable_2="PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Cdk2_CycErem"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="PCdk2_CycErem"/>
<map_variables variable_1="PCdk2_CycErem" variable_2="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Cyc_total" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xic"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xic_Cdk2_CycE"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xic_total" component_2="Xicrem"/>
<map_variables variable_1="Xicrem" variable_2="Xicrem"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
</connection>
<connection>
<map_components component_1="Deg_a" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Deg_a" variable_2="Deg_a"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic" variable_2="Xic"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycE" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycE" component_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
<map_variables variable_1="Xic_Cdk2_CycE" variable_2="Xic_Cdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycE" component_2="Wee1_a"/>
<map_variables variable_1="Wee1_a" variable_2="Wee1_a"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycE" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycE" variable_2="Xic_PCdk2_CycE"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycE" component_2="Wee1_a"/>
<map_variables variable_1="Wee1_a" variable_2="Wee1_a"/>
</connection>
<connection>
<map_components component_1="Xicrem" component_2="Xic_Cdk2_CycErem"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xicrem" component_2="Deg_a"/>
<map_variables variable_1="Deg_a" variable_2="Deg_a"/>
</connection>
<connection>
<map_components component_1="Xicrem" component_2="Xic_PCdk2_CycErem"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycE" component_2="kinetic_parameters"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k25A" variable_2="k25A"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycE" component_2="kinetic_parameters"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k25A" variable_2="k25A"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
</connection>
<connection>
<map_components component_1="Cdk2_CycErem" component_2="kinetic_parameters"/>
<map_variables variable_1="kedeg" variable_2="kedeg"/>
<map_variables variable_1="kxdeg" variable_2="kxdeg"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
<map_variables variable_1="Cdk2_CycErem" variable_2="Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="PCdk2_CycErem" component_2="kinetic_parameters"/>
<map_variables variable_1="kedeg" variable_2="kedeg"/>
<map_variables variable_1="kxdeg" variable_2="kxdeg"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
<map_variables variable_1="PCdk2_CycErem" variable_2="PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xic" component_2="kinetic_parameters"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycE" component_2="kinetic_parameters"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k25A" variable_2="k25A"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycE" component_2="kinetic_parameters"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k25A" variable_2="k25A"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
</connection>
<connection>
<map_components component_1="Xic_Cdk2_CycErem" component_2="kinetic_parameters"/>
<map_variables variable_1="kedeg" variable_2="kedeg"/>
<map_variables variable_1="kxdeg" variable_2="kxdeg"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
<map_variables variable_1="Xic_Cdk2_CycErem" variable_2="Xic_Cdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xic_PCdk2_CycErem" component_2="kinetic_parameters"/>
<map_variables variable_1="kedeg" variable_2="kedeg"/>
<map_variables variable_1="kxdeg" variable_2="kxdeg"/>
<map_variables variable_1="kon" variable_2="kon"/>
<map_variables variable_1="koff" variable_2="koff"/>
<map_variables variable_1="phi" variable_2="phi"/>
<map_variables variable_1="kassoc" variable_2="kassoc"/>
<map_variables variable_1="kdissoc" variable_2="kdissoc"/>
<map_variables variable_1="Deg" variable_2="Deg"/>
<map_variables variable_1="Xic_PCdk2_CycErem" variable_2="Xic_PCdk2_CycErem"/>
</connection>
<connection>
<map_components component_1="Xicrem" component_2="kinetic_parameters"/>
<map_variables variable_1="kedeg" variable_2="kedeg"/>
<map_variables variable_1="kxdeg" variable_2="kxdeg"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Seq rdf:about="rdf:#f4650cbb-b069-4e9a-bc91-2cffe5eae158">
<rdf:li rdf:resource="rdf:#ea355f8a-989d-45d7-bcf5-c179572442d9"/>
<rdf:li rdf:resource="rdf:#5a05b438-9a8a-4d65-98e6-ce7439ee307f"/>
<rdf:li rdf:resource="rdf:#36307734-2d59-4211-a7e6-4f450960a176"/>
<rdf:li rdf:resource="rdf:#914f7ff4-2258-4cc0-a676-55cd868a35bc"/>
</rdf:Seq>
<rdf:Description rdf:about="rdf:#27669ebf-5877-42df-bb2b-cfbb1df3e046">
<dc:subject xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#a4e3d3ba-14d1-4ff6-b525-2634fd1e4886"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ea355f8a-989d-45d7-bcf5-c179572442d9">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#0f052593-5157-47d7-a148-c7f3e8131a6b"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ef4a3516-aa43-41ee-ad1b-7189346e2564">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#3bb87869-9721-4fde-b2b4-2ff7de5f9173"/>
<rdf:value>Initial conditions were added and several equations modified to allow the model to run.</rdf:value>
<cmeta:modifier rdf:resource="rdf:#eb749fe1-d193-4bba-9280-a86ed7f32dd5"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#12318d81-5011-483e-bbd2-10e769f6fe79">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">John</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Tyson</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#67ce8887-6cff-42f9-a18e-1703e4fc0789">
<bqs:Pubmed_id xmlns:bqs="http://www.cellml.org/bqs/1.0#">12914904</bqs:Pubmed_id>
<bqs:JournalArticle xmlns:bqs="http://www.cellml.org/bqs/1.0#" rdf:resource="rdf:#be35d4df-8a3e-4aa8-a2e1-68d5bed80861"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#95525b68-af43-4574-bd6f-e285014b79e6">
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#2af321fa-ead5-4b7a-b8ef-bc980577a050"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1341d665-d2a5-48f8-99c5-983c52058f0e">
<dcterms:modified xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#2cf6a627-0dc1-4279-9999-f398200c18bf"/>
<rdf:value>Added cmeta id's to several variables</rdf:value>
<cmeta:modifier rdf:resource="rdf:#95525b68-af43-4574-bd6f-e285014b79e6"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2cf6a627-0dc1-4279-9999-f398200c18bf">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2009-02-18T12:08:09+13:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#ciliberto_2003">
<ns7:simulation xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" rdf:resource="rdf:#$9owyl"/>
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Ciliberto et al.'s 2003 kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus laevis embryos.</dc:title>
<cmeta:comment rdf:resource="rdf:#01433d8d-3e6d-4477-b253-1d5a4cc13842"/>
<bqs:reference xmlns:bqs="http://www.cellml.org/bqs/1.0#" rdf:resource="rdf:#27669ebf-5877-42df-bb2b-cfbb1df3e046"/>
<bqs:reference xmlns:bqs="http://www.cellml.org/bqs/1.0#" rdf:resource="rdf:#67ce8887-6cff-42f9-a18e-1703e4fc0789"/>
<bqs:reference xmlns:bqs="http://www.cellml.org/bqs/1.0#" rdf:parseType="Resource">
<dc:subject xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:parseType="Resource">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>
<rdf:Bag>
<rdf:li>cyclin e</rdf:li>
<rdf:li>cdk2</rdf:li>
<rdf:li>cell cycle</rdf:li>
<rdf:li>xenopus</rdf:li>
</rdf:Bag>
</rdf:value>
</dc:subject>
</bqs:reference>
<cmeta:species>Xenopus laevis</cmeta:species>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d280972e-a2ed-4db3-aebe-a6e8ff57729f">
<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#$aowyl">
<rdf:rest rdf:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
<rdf:first rdf:resource="rdf:#$bowyl"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0f7572f6-c9dd-489b-a953-99e1b6bfc24a">
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#70684c2b-0c03-4b2b-b5e3-4e7291f7310a"/>
<rdf:value>This CellML version of the model has been checked in PCEnv and the model runs to replicate the results in the original published paper. This model uses the initial conditions that recreate the results in figure 6. The model runs in COR but the duration of the model is too long for the results to be properly displayed in COR. The units have been checked and are consistent.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#914f7ff4-2258-4cc0-a676-55cd868a35bc">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#a09ca2b7-b891-4757-9acf-38ddaf6d3905"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#2af321fa-ead5-4b7a-b8ef-bc980577a050">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lim</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#$9owyl">
<ns7:boundIntervals xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" rdf:resource="rdf:#$aowyl"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5db84f90-bc64-4635-a48d-1d431b9cb145">
<vCard:Orgname xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">The University of Auckland</vCard:Orgname>
<vCard:Orgunit xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Auckland Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fc4f3954-2894-49c1-b2d9-7899d5203ba4">
<vCard:ORG xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#5db84f90-bc64-4635-a48d-1d431b9cb145"/>
<vCard:EMAIL xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#1eae1e22-fff4-433c-b08e-01ff3794ea59"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#978c3daa-9ca3-46aa-95d1-0c023836ea0c"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a4e3d3ba-14d1-4ff6-b525-2634fd1e4886">
<bqs:subject_type xmlns:bqs="http://www.cellml.org/bqs/1.0#">keyword</bqs:subject_type>
<rdf:value>cell cycle</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3bb87869-9721-4fde-b2b4-2ff7de5f9173">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2008-12-16T10:34:17+13:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#978c3daa-9ca3-46aa-95d1-0c023836ea0c">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lloyd</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#be35d4df-8a3e-4aa8-a2e1-68d5bed80861">
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#f4650cbb-b069-4e9a-bc91-2cffe5eae158"/>
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">A kinetic model of the cyclin E/Cdk2 developmental timer in Xenopus</dc:title>
<bqs:volume xmlns:bqs="http://www.cellml.org/bqs/1.0#">104</bqs:volume>
<bqs:first_page xmlns:bqs="http://www.cellml.org/bqs/1.0#">573</bqs:first_page>
<bqs:Journal xmlns:bqs="http://www.cellml.org/bqs/1.0#" rdf:resource="rdf:#d5dac004-7aa3-4603-a9c3-90933933f25d"/>
<dcterms:issued xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#be558ec5-31cf-4987-b758-a47a3cf130ba"/>
<bqs:last_page xmlns:bqs="http://www.cellml.org/bqs/1.0#">589</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#$bowyl">
<ns7:endingValue xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#">16</ns7:endingValue>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4eba35f4-5dd3-41b8-b5ed-72cd9b660b0e">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Matthew</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Petrus</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d5dac004-7aa3-4603-a9c3-90933933f25d">
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Biophysical Chemistry</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#36307734-2d59-4211-a7e6-4f450960a176">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#12318d81-5011-483e-bbd2-10e769f6fe79"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#eb749fe1-d193-4bba-9280-a86ed7f32dd5">
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#4e62ed80-3578-4c51-8856-23866704c6c0"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#be558ec5-31cf-4987-b758-a47a3cf130ba">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2003-07-01</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher xmlns:dc="http://purl.org/dc/elements/1.1/">The University of Auckland, Auckland Bioengineering Institute</dc:publisher>
<cmeta:comment rdf:resource="rdf:#0f7572f6-c9dd-489b-a953-99e1b6bfc24a"/>
<dcterms:created xmlns:dcterms="http://purl.org/dc/terms/" rdf:resource="rdf:#5036bea4-b6c7-4beb-8ab6-cca7f9ec67f5"/>
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#fc4f3954-2894-49c1-b2d9-7899d5203ba4"/>
<cmeta:modification rdf:resource="rdf:#1341d665-d2a5-48f8-99c5-983c52058f0e"/>
<cmeta:modification rdf:resource="rdf:#ef4a3516-aa43-41ee-ad1b-7189346e2564"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4e62ed80-3578-4c51-8856-23866704c6c0">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Lim</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1eae1e22-fff4-433c-b08e-01ff3794ea59">
<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5a05b438-9a8a-4d65-98e6-ce7439ee307f">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" rdf:resource="rdf:#4eba35f4-5dd3-41b8-b5ed-72cd9b660b0e"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#01433d8d-3e6d-4477-b253-1d5a4cc13842">
<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#d280972e-a2ed-4db3-aebe-a6e8ff57729f"/>
<rdf:value>This is the CellML description of Ciliberto et al.'s 2003 kinetic
model of the cyclin E/Cdk2 developmental timer in Xenopus laevis
embryos.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#70684c2b-0c03-4b2b-b5e3-4e7291f7310a">
<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean Lim</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a09ca2b7-b891-4757-9acf-38ddaf6d3905">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jill</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Sible</vCard:Family>
<vCard:Other xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">C</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#5036bea4-b6c7-4beb-8ab6-cca7f9ec67f5">
<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2003-12-08T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#0f052593-5157-47d7-a148-c7f3e8131a6b">
<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Andrea</vCard:Given>
<vCard:Family xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Ciliberto</vCard:Family>
</rdf:Description>
</rdf:RDF>
</model>
