- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-06-17 15:27:17+12:00
- Desc:
- committing version03 of novak_tyson_1997
- Permanent Source URI:
- http://models.cellml.org/workspace/novak_tyson_1997/rawfile/7cdccc07c75645ebdf6f90bdb0ca517e80fae3d0/novak_tyson_1997.cellml
<?xml version='1.0' encoding='utf-8'?>
<!--
This CellML file was generated on 9/12/2008 at 10:53:37 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/
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Modelling the Control of DNA Replication in Fission Yeast</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 CellML version of the model has been checked in COR and PCEnv and the model runs to replicate the results in the original published paper. The units have been checked and are consistent.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
The molecular mechanisms which underlie the control of the eukaryotic cell cycle are beginning to be elucidated by studies of fission yeast. One event of particular importance is the initiation of DNA replication (the S phase). Tight controls usually exist to prevent repeated phases of DNA replication without nuclear (mitosis) and cellular (cytokinesis) division occurring. Similarly, until DNA replication is complete, the initiation of mitosis is inhibited.
</para>
<para>
Fission yeast cells carrying the mutant genes <emphasis>wee1<superscript>-</superscript>
</emphasis> and <emphasis>cdc25<superscript>OP</superscript>
</emphasis> initiate mitosis before DNA replication is complete, suggesting that the products of the wild type genes play an essential role in the G<subscript>2</subscript> checkpoint controls that delay division until DNA replication is complete. Similarly, in cells with a mutant copy of either the <emphasis>cdc2</emphasis>, <emphasis>cdc13</emphasis>, or <emphasis>Rum1</emphasis> genes, the G<subscript>1</subscript> checkpoint fails, and DNA synthesis begins before the cell has divided, resulting in a polyploid cell.
</para>
<para>
Based on this experimental data, Bela Novak and John Tyson have developed a mathematical model describing the control of DNA replication in fission yeast. Using principles of biochemical kinetics (mass action and Michaelis-Menten reaction kinetics), the reaction mechanism shown in the figure below is converted into a set of differential equations. These rate equations describe how the concentrations of the main control variables change over time.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.pnas.org/cgi/content/abstract/94/17/9147">Modeling the control of DNA replication in fission yeast</ulink>, Bela Novak and John J. Tyson, 1997, <ulink url="http://www.pnas.org/">
<emphasis>Proceedings of the National Academy of Sciences</emphasis>
</ulink>, 94, 9147-9152. (A <ulink url="http://www.pnas.org/cgi/reprint/94/17/9147.pdf">PDF version</ulink> of the article is available to subscribers on the journal website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=9256450&dopt=Abstract">PubMed ID: 9256450</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="novak_1997.png"/>
</imageobject>
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<caption>A schematic diagram of the reaction mechanism which describes the G<subscript>1</subscript>/S and G<subscript>2</subscript>/M controls in fission yeast.</caption>
</informalfigure>
<para>
Please note that the following switches in the published model are not included in the CellML description:
<itemizedlist>
<listitem>
<para>
(i) When SPF crosses 0.1 from below, S phase is initiated (Start).
</para>
</listitem>
<listitem>
<para>
(ii) When UbE crosses 0.1 from above, the cell divides functionally (mass->mass/2), although visible cytokinesis may be delayed.
</para>
</listitem>
<listitem>
<para>
(iii) 60 min after Start, kp is divided by 2, and at cell division kp is multiplied by 2.
</para>
</listitem>
</itemizedlist>
(taken from Table 1 of the cited reference).
</para>
</sect1>
</article>
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<variable units="first_order_rate_constant" public_interface="in" name="kw"/>
<variable units="dimensionless" public_interface="in" name="Kmwr"/>
<variable units="dimensionless" public_interface="in" name="Kmw"/>
<variable units="dimensionless" public_interface="in" name="MPF"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Wee1</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kwr</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>Wee1</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Kmwr</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>Wee1</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kw</ci>
<ci>MPF</ci>
<ci>Wee1</ci>
</apply>
<apply>
<plus/>
<ci>Kmw</ci>
<ci>Wee1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PG2">
<variable units="dimensionless" public_interface="out" cmeta:id="PG2_PG2" name="PG2" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2"/>
<variable units="first_order_rate_constant" public_interface="in" name="k7"/>
<variable units="first_order_rate_constant" public_interface="in" name="k4"/>
<variable units="first_order_rate_constant" public_interface="in" name="k25"/>
<variable units="first_order_rate_constant" public_interface="in" name="kwee"/>
<variable units="first_order_rate_constant" public_interface="in" name="k7r"/>
<variable units="dimensionless" public_interface="in" name="PG2R"/>
<variable units="dimensionless" public_interface="in" name="G2K"/>
<variable units="dimensionless" public_interface="in" name="R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PG2</ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci>kwee</ci>
<ci>G2K</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k7r</ci>
<ci>k4</ci>
</apply>
<ci>PG2R</ci>
</apply>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k25</ci>
<ci>k2</ci>
<apply>
<times/>
<ci>k7</ci>
<ci>R</ci>
</apply>
</apply>
<ci>PG2</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="G1R">
<variable units="dimensionless" public_interface="out" cmeta:id="G1R_G1R" name="G1R" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="k8"/>
<variable units="first_order_rate_constant" public_interface="in" name="k4"/>
<variable units="first_order_rate_constant" public_interface="in" name="k6_"/>
<variable units="first_order_rate_constant" public_interface="in" name="k8r"/>
<variable units="dimensionless" public_interface="in" name="G1K"/>
<variable units="dimensionless" public_interface="in" name="R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>G1R</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k8</ci>
<ci>R</ci>
<ci>G1K</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k8r</ci>
<ci>k4</ci>
<ci>k6_</ci>
</apply>
<ci>G1R</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PG2R">
<variable units="dimensionless" public_interface="out" name="PG2R" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="k7"/>
<variable units="first_order_rate_constant" public_interface="in" name="k4"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2_"/>
<variable units="first_order_rate_constant" public_interface="in" name="k7r"/>
<variable units="dimensionless" public_interface="in" name="PG2"/>
<variable units="dimensionless" public_interface="in" name="R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>PG2R</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k7</ci>
<ci>R</ci>
<ci>PG2</ci>
</apply>
<apply>
<times/>
<apply>
<plus/>
<ci>k7r</ci>
<ci>k4</ci>
<ci>k2</ci>
<ci>k2_</ci>
</apply>
<ci>PG2R</ci>
</apply>
</apply>
</apply>
</math>
</component>
<component name="UbE">
<variable units="dimensionless" public_interface="out" cmeta:id="UbE_UbE" name="UbE" initial_value="1"/>
<variable units="first_order_rate_constant" public_interface="in" name="kur"/>
<variable units="first_order_rate_constant" public_interface="in" name="ku"/>
<variable units="dimensionless" public_interface="in" name="Kmur"/>
<variable units="dimensionless" public_interface="in" name="Kmu"/>
<variable units="dimensionless" public_interface="in" name="IE"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>UbE</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>ku</ci>
<ci>IE</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>UbE</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Kmu</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>UbE</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kur</ci>
<ci>UbE</ci>
</apply>
<apply>
<plus/>
<ci>Kmur</ci>
<ci>UbE</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="mass">
<variable units="dimensionless" public_interface="out" name="mass" initial_value="0.5"/>
<variable units="first_order_rate_constant" public_interface="in" name="mu"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>mass</ci>
</apply>
<apply>
<times/>
<ci>mu</ci>
<ci>mass</ci>
</apply>
</apply>
</math>
</component>
<component name="Cdc25">
<variable units="dimensionless" public_interface="out" cmeta:id="Cdc25_Cdc25" name="Cdc25" initial_value="0"/>
<variable units="first_order_rate_constant" public_interface="in" name="kcr"/>
<variable units="first_order_rate_constant" public_interface="in" name="kc"/>
<variable units="dimensionless" public_interface="in" name="Kmcr"/>
<variable units="dimensionless" public_interface="in" name="Kmc"/>
<variable units="dimensionless" public_interface="in" name="MPF"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cdc25</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kc</ci>
<ci>MPF</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
<ci>Cdc25</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Kmc</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<ci>Cdc25</ci>
</apply>
</apply>
<apply>
<divide/>
<apply>
<times/>
<ci>kcr</ci>
<ci>Cdc25</ci>
</apply>
<apply>
<plus/>
<ci>Kmcr</ci>
<ci>Cdc25</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="Cig2_total">
<variable units="dimensionless" public_interface="out" name="Cig2_total"/>
<variable units="dimensionless" public_interface="in" name="G1K"/>
<variable units="dimensionless" public_interface="in" name="G1R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Cig2_total</ci>
<apply>
<plus/>
<ci>G1K</ci>
<ci>G1R</ci>
</apply>
</apply>
</math>
</component>
<component name="Rum1_total">
<variable units="dimensionless" public_interface="out" name="Rum1_total"/>
<variable units="dimensionless" public_interface="in" name="R"/>
<variable units="dimensionless" public_interface="in" name="G1R"/>
<variable units="dimensionless" public_interface="in" name="G2R"/>
<variable units="dimensionless" public_interface="in" name="PG2R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Rum1_total</ci>
<apply>
<plus/>
<ci>R</ci>
<ci>G1R</ci>
<ci>G2R</ci>
<ci>PG2R</ci>
</apply>
</apply>
</math>
</component>
<component name="Cdc13_total">
<variable units="dimensionless" public_interface="out" name="Cdc13_total"/>
<variable units="dimensionless" public_interface="in" name="G2K"/>
<variable units="dimensionless" public_interface="in" name="G2R"/>
<variable units="dimensionless" public_interface="in" name="PG2"/>
<variable units="dimensionless" public_interface="in" name="PG2R"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>Cdc13_total</ci>
<apply>
<plus/>
<ci>G2K</ci>
<ci>G2R</ci>
<ci>PG2</ci>
<ci>PG2R</ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_2="environment" component_1="G2K"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="R"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="G1K"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="G2R"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="IE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="UbE2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Wee1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="PG2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="G1R"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="PG2R"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="UbE"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="mass"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cdc25"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cig2_total"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Rum1_total"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cdc13_total"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="G2K" component_1="concentration_variables"/>
<map_variables variable_2="G2K" variable_1="G2K"/>
</connection>
<connection>
<map_components component_2="R" component_1="concentration_variables"/>
<map_variables variable_2="SPF" variable_1="SPF"/>
</connection>
<connection>
<map_components component_2="G1K" component_1="concentration_variables"/>
<map_variables variable_2="G1K" variable_1="G1K"/>
</connection>
<connection>
<map_components component_2="IE" component_1="concentration_variables"/>
<map_variables variable_2="MPF" variable_1="MPF"/>
</connection>
<connection>
<map_components component_2="UbE2" component_1="concentration_variables"/>
<map_variables variable_2="MPF" variable_1="MPF"/>
</connection>
<connection>
<map_components component_2="Wee1" component_1="concentration_variables"/>
<map_variables variable_2="MPF" variable_1="MPF"/>
</connection>
<connection>
<map_components component_2="PG2" component_1="concentration_variables"/>
<map_variables variable_2="PG2" variable_1="PG2"/>
</connection>
<connection>
<map_components component_2="Cdc25" component_1="concentration_variables"/>
<map_variables variable_2="MPF" variable_1="MPF"/>
</connection>
<connection>
<map_components component_2="G2K" component_1="rate_constants"/>
<map_variables variable_2="k1" variable_1="k1"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="kwee" variable_1="kwee"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k7r" variable_1="k7r"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k25" variable_1="k25"/>
</connection>
<connection>
<map_components component_2="R" component_1="rate_constants"/>
<map_variables variable_2="k3" variable_1="k3"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="kp" variable_1="kp"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k7r" variable_1="k7r"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k2_" variable_1="k2_"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k8r" variable_1="k8r"/>
<map_variables variable_2="k6_" variable_1="k6_"/>
<map_variables variable_2="Kmp" variable_1="Kmp"/>
</connection>
<connection>
<map_components component_2="G1K" component_1="rate_constants"/>
<map_variables variable_2="k5" variable_1="k5"/>
<map_variables variable_2="k6" variable_1="k6"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k8r" variable_1="k8r"/>
<map_variables variable_2="k4" variable_1="k4"/>
</connection>
<connection>
<map_components component_2="G2R" component_1="rate_constants"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k7r" variable_1="k7r"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k2_" variable_1="k2_"/>
</connection>
<connection>
<map_components component_2="IE" component_1="rate_constants"/>
<map_variables variable_2="ki" variable_1="ki"/>
<map_variables variable_2="kir" variable_1="kir"/>
<map_variables variable_2="Kmi" variable_1="Kmi"/>
<map_variables variable_2="Kmir" variable_1="Kmir"/>
</connection>
<connection>
<map_components component_2="UbE2" component_1="rate_constants"/>
<map_variables variable_2="UbE2" variable_1="UbE2"/>
<map_variables variable_2="ku2" variable_1="ku2"/>
<map_variables variable_2="kur2" variable_1="kur2"/>
<map_variables variable_2="Kmu2" variable_1="Kmu2"/>
<map_variables variable_2="Kmur2" variable_1="Kmur2"/>
</connection>
<connection>
<map_components component_2="Wee1" component_1="rate_constants"/>
<map_variables variable_2="Wee1" variable_1="Wee1"/>
<map_variables variable_2="kw" variable_1="kw"/>
<map_variables variable_2="kwr" variable_1="kwr"/>
<map_variables variable_2="Kmw" variable_1="Kmw"/>
<map_variables variable_2="Kmwr" variable_1="Kmwr"/>
</connection>
<connection>
<map_components component_2="G1R" component_1="rate_constants"/>
<map_variables variable_2="k8" variable_1="k8"/>
<map_variables variable_2="k8r" variable_1="k8r"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k6_" variable_1="k6_"/>
</connection>
<connection>
<map_components component_2="PG2R" component_1="rate_constants"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k7r" variable_1="k7r"/>
<map_variables variable_2="k4" variable_1="k4"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k2_" variable_1="k2_"/>
</connection>
<connection>
<map_components component_2="PG2" component_1="rate_constants"/>
<map_variables variable_2="kwee" variable_1="kwee"/>
<map_variables variable_2="k25" variable_1="k25"/>
<map_variables variable_2="k2" variable_1="k2"/>
<map_variables variable_2="k7" variable_1="k7"/>
<map_variables variable_2="k7r" variable_1="k7r"/>
<map_variables variable_2="k4" variable_1="k4"/>
</connection>
<connection>
<map_components component_2="UbE" component_1="rate_constants"/>
<map_variables variable_2="UbE" variable_1="UbE"/>
<map_variables variable_2="ku" variable_1="ku"/>
<map_variables variable_2="kur" variable_1="kur"/>
<map_variables variable_2="Kmu" variable_1="Kmu"/>
<map_variables variable_2="Kmur" variable_1="Kmur"/>
</connection>
<connection>
<map_components component_2="mass" component_1="rate_constants"/>
<map_variables variable_2="mu" variable_1="mu"/>
</connection>
<connection>
<map_components component_2="Cdc25" component_1="rate_constants"/>
<map_variables variable_2="Cdc25" variable_1="Cdc25"/>
<map_variables variable_2="kc" variable_1="kc"/>
<map_variables variable_2="kcr" variable_1="kcr"/>
<map_variables variable_2="Kmc" variable_1="Kmc"/>
<map_variables variable_2="Kmcr" variable_1="Kmcr"/>
</connection>
<connection>
<map_components component_2="R" component_1="G2K"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="G2K" variable_1="G2K"/>
</connection>
<connection>
<map_components component_2="G2R" component_1="G2K"/>
<map_variables variable_2="G2R" variable_1="G2R"/>
<map_variables variable_2="G2K" variable_1="G2K"/>
</connection>
<connection>
<map_components component_2="PG2" component_1="G2K"/>
<map_variables variable_2="PG2" variable_1="PG2"/>
<map_variables variable_2="G2K" variable_1="G2K"/>
</connection>
<connection>
<map_components component_2="mass" component_1="R"/>
<map_variables variable_2="mass" variable_1="mass"/>
</connection>
<connection>
<map_components component_2="PG2" component_1="R"/>
<map_variables variable_2="PG2" variable_1="PG2"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="G2R" component_1="R"/>
<map_variables variable_2="G2R" variable_1="G2R"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="PG2R" component_1="R"/>
<map_variables variable_2="PG2R" variable_1="PG2R"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="G1K" component_1="R"/>
<map_variables variable_2="G1K" variable_1="G1K"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="G1R" component_1="R"/>
<map_variables variable_2="G1R" variable_1="G1R"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="G1R" component_1="G1K"/>
<map_variables variable_2="G1R" variable_1="G1R"/>
<map_variables variable_2="G1K" variable_1="G1K"/>
</connection>
<connection>
<map_components component_2="PG2R" component_1="PG2"/>
<map_variables variable_2="PG2R" variable_1="PG2R"/>
<map_variables variable_2="PG2" variable_1="PG2"/>
</connection>
<connection>
<map_components component_2="IE" component_1="UbE"/>
<map_variables variable_2="IE" variable_1="IE"/>
</connection>
<connection>
<map_components component_2="G1K" component_1="Cig2_total"/>
<map_variables variable_2="G1K" variable_1="G1K"/>
</connection>
<connection>
<map_components component_2="G1R" component_1="Cig2_total"/>
<map_variables variable_2="G1R" variable_1="G1R"/>
</connection>
<connection>
<map_components component_2="R" component_1="Rum1_total"/>
<map_variables variable_2="R" variable_1="R"/>
</connection>
<connection>
<map_components component_2="G1R" component_1="Rum1_total"/>
<map_variables variable_2="G1R" variable_1="G1R"/>
</connection>
<connection>
<map_components component_2="G2R" component_1="Rum1_total"/>
<map_variables variable_2="G2R" variable_1="G2R"/>
</connection>
<connection>
<map_components component_2="PG2R" component_1="Rum1_total"/>
<map_variables variable_2="PG2R" variable_1="PG2R"/>
</connection>
<connection>
<map_components component_2="G2K" component_1="Cdc13_total"/>
<map_variables variable_2="G2K" variable_1="G2K"/>
</connection>
<connection>
<map_components component_2="G2R" component_1="Cdc13_total"/>
<map_variables variable_2="G2R" variable_1="G2R"/>
</connection>
<connection>
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<rdf:value>Fixed bullet points in the documentation.</rdf:value>
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