<?xml version="1.0"?>
<!--
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/
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" cmeta:id="novak_1997" name="novak_1997">
<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>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in both COR and OpenCell to replicate the results in the original published paper. The units have been checked and they are consistent. Please note that this CellML model is based on the equations from the main body of the paper, not the appendix, and so it does not reproduce the cyclical graphs in the paper. The model does however produce results which match the first cycle of the graphs in the paper. Until events can be described in CellML we are unable to capture the switches in this model.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: A central event in the eukaryotic cell cycle is the decision to commence DNA replication (S phase). Strict controls normally operate to prevent repeated rounds of DNA replication without intervening mitoses ("endoreplication") or initiation of mitosis before DNA is fully replicated ("mitotic catastrophe"). Some of the genetic interactions involved in these controls have recently been identified in yeast. From this evidence we propose a molecular mechanism of "Start" control in Schizosaccharomyces pombe. Using established principles of biochemical kinetics, we compare the properties of this model in detail with the observed behavior of various mutant strains of fission yeast: wee1(-) (size control at Start), cdc13Delta and rum1(OP) (endoreplication), and wee1(-) rum1Delta (rapid division cycles of diminishing cell size). We discuss essential features of the mechanism that are responsible for characteristic properties of Start control in fission yeast, to expose our proposal to crucial experimental tests.
</para>
<para>
The original paper reference is cited below:
</para>
<para>
Modeling the control of DNA replication in fission yeast, Bela Novak and John J. Tyson, 1997, <emphasis>Proceedings of the National Academy of Sciences</emphasis>, 94, 9147-9152. <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>
</mediaobject>
<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>
</documentation>
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<ci>Wee1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="PG2">
<variable cmeta:id="PG2_PG2" initial_value="0" name="PG2" public_interface="out" units="dimensionless"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k7" public_interface="in" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<variable name="k25" public_interface="in" units="first_order_rate_constant"/>
<variable name="kwee" public_interface="in" units="first_order_rate_constant"/>
<variable name="k7r" public_interface="in" units="first_order_rate_constant"/>
<variable name="PG2R" public_interface="in" units="dimensionless"/>
<variable name="G2K" public_interface="in" units="dimensionless"/>
<variable name="R" 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>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 cmeta:id="G1R_G1R" initial_value="0" name="G1R" public_interface="out" units="dimensionless"/>
<variable name="k8" public_interface="in" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<variable name="k6_" public_interface="in" units="first_order_rate_constant"/>
<variable name="k8r" public_interface="in" units="first_order_rate_constant"/>
<variable name="G1K" public_interface="in" units="dimensionless"/>
<variable name="R" 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>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 initial_value="0" name="PG2R" public_interface="out" units="dimensionless"/>
<variable name="k7" public_interface="in" units="first_order_rate_constant"/>
<variable name="k4" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2" public_interface="in" units="first_order_rate_constant"/>
<variable name="k2_" public_interface="in" units="first_order_rate_constant"/>
<variable name="k7r" public_interface="in" units="first_order_rate_constant"/>
<variable name="PG2" public_interface="in" units="dimensionless"/>
<variable name="R" 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>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 cmeta:id="UbE_UbE" initial_value="1" name="UbE" public_interface="out" units="dimensionless"/>
<variable name="kur" public_interface="in" units="first_order_rate_constant"/>
<variable name="ku" public_interface="in" units="first_order_rate_constant"/>
<variable name="Kmur" public_interface="in" units="dimensionless"/>
<variable name="Kmu" public_interface="in" units="dimensionless"/>
<variable name="IE" 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>UbE</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>ku</ci>
<ci>IE</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>UbE</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Kmu</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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 initial_value="0.5" name="mass" public_interface="out" units="dimensionless"/>
<variable name="mu" public_interface="in" units="first_order_rate_constant"/>
<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>mass</ci>
</apply>
<apply>
<times/>
<ci>mu</ci>
<ci>mass</ci>
</apply>
</apply>
</math>
</component>
<component name="Cdc25">
<variable cmeta:id="Cdc25_Cdc25" initial_value="0" name="Cdc25" public_interface="out" units="dimensionless"/>
<variable name="kcr" public_interface="in" units="first_order_rate_constant"/>
<variable name="kc" public_interface="in" units="first_order_rate_constant"/>
<variable name="Kmcr" public_interface="in" units="dimensionless"/>
<variable name="Kmc" public_interface="in" units="dimensionless"/>
<variable name="MPF" 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>Cdc25</ci>
</apply>
<apply>
<minus/>
<apply>
<divide/>
<apply>
<times/>
<ci>kc</ci>
<ci>MPF</ci>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless">1</cn>
<ci>Cdc25</ci>
</apply>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<ci>Kmc</ci>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" 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 name="Cig2_total" public_interface="out" units="dimensionless"/>
<variable name="G1K" public_interface="in" units="dimensionless"/>
<variable name="G1R" 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>Cig2_total</ci>
<apply>
<plus/>
<ci>G1K</ci>
<ci>G1R</ci>
</apply>
</apply>
</math>
</component>
<component name="Rum1_total">
<variable name="Rum1_total" public_interface="out" units="dimensionless"/>
<variable name="R" public_interface="in" units="dimensionless"/>
<variable name="G1R" public_interface="in" units="dimensionless"/>
<variable name="G2R" public_interface="in" units="dimensionless"/>
<variable name="PG2R" 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>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 name="Cdc13_total" public_interface="out" units="dimensionless"/>
<variable name="G2K" public_interface="in" units="dimensionless"/>
<variable name="G2R" public_interface="in" units="dimensionless"/>
<variable name="PG2" public_interface="in" units="dimensionless"/>
<variable name="PG2R" 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>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_1="G2K" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="R" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="G1K" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="G2R" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="IE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="UbE2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Wee1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="PG2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="G1R" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="PG2R" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="UbE" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="mass" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cdc25" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cig2_total" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Rum1_total" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="Cdc13_total" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="G2K"/>
<map_variables variable_1="G2K" variable_2="G2K"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="R"/>
<map_variables variable_1="SPF" variable_2="SPF"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="G1K"/>
<map_variables variable_1="G1K" variable_2="G1K"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="IE"/>
<map_variables variable_1="MPF" variable_2="MPF"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="UbE2"/>
<map_variables variable_1="MPF" variable_2="MPF"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="Wee1"/>
<map_variables variable_1="MPF" variable_2="MPF"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="PG2"/>
<map_variables variable_1="PG2" variable_2="PG2"/>
</connection>
<connection>
<map_components component_1="concentration_variables" component_2="Cdc25"/>
<map_variables variable_1="MPF" variable_2="MPF"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="G2K"/>
<map_variables variable_1="k1" variable_2="k1"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k7r" variable_2="k7r"/>
<map_variables variable_1="k4" variable_2="k4"/>
<map_variables variable_1="k25" variable_2="k25"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="R"/>
<map_variables variable_1="k3" variable_2="k3"/>
<map_variables variable_1="k4" variable_2="k4"/>
<map_variables variable_1="kp" variable_2="kp"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k7r" variable_2="k7r"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k2_" variable_2="k2_"/>
<map_variables variable_1="k8" variable_2="k8"/>
<map_variables variable_1="k8r" variable_2="k8r"/>
<map_variables variable_1="k6_" variable_2="k6_"/>
<map_variables variable_1="Kmp" variable_2="Kmp"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="G1K"/>
<map_variables variable_1="k5" variable_2="k5"/>
<map_variables variable_1="k6" variable_2="k6"/>
<map_variables variable_1="k8" variable_2="k8"/>
<map_variables variable_1="k8r" variable_2="k8r"/>
<map_variables variable_1="k4" variable_2="k4"/>
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<connection>
<map_components component_1="rate_constants" component_2="G2R"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k7r" variable_2="k7r"/>
<map_variables variable_1="k4" variable_2="k4"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k2_" variable_2="k2_"/>
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<connection>
<map_components component_1="rate_constants" component_2="IE"/>
<map_variables variable_1="ki" variable_2="ki"/>
<map_variables variable_1="kir" variable_2="kir"/>
<map_variables variable_1="Kmi" variable_2="Kmi"/>
<map_variables variable_1="Kmir" variable_2="Kmir"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="UbE2"/>
<map_variables variable_1="UbE2" variable_2="UbE2"/>
<map_variables variable_1="ku2" variable_2="ku2"/>
<map_variables variable_1="kur2" variable_2="kur2"/>
<map_variables variable_1="Kmu2" variable_2="Kmu2"/>
<map_variables variable_1="Kmur2" variable_2="Kmur2"/>
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<connection>
<map_components component_1="rate_constants" component_2="Wee1"/>
<map_variables variable_1="Wee1" variable_2="Wee1"/>
<map_variables variable_1="kw" variable_2="kw"/>
<map_variables variable_1="kwr" variable_2="kwr"/>
<map_variables variable_1="Kmw" variable_2="Kmw"/>
<map_variables variable_1="Kmwr" variable_2="Kmwr"/>
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<connection>
<map_components component_1="rate_constants" component_2="G1R"/>
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<map_variables variable_1="k8r" variable_2="k8r"/>
<map_variables variable_1="k4" variable_2="k4"/>
<map_variables variable_1="k6_" variable_2="k6_"/>
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<connection>
<map_components component_1="rate_constants" component_2="PG2R"/>
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<map_variables variable_1="k7r" variable_2="k7r"/>
<map_variables variable_1="k4" variable_2="k4"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k2_" variable_2="k2_"/>
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<connection>
<map_components component_1="rate_constants" component_2="PG2"/>
<map_variables variable_1="kwee" variable_2="kwee"/>
<map_variables variable_1="k25" variable_2="k25"/>
<map_variables variable_1="k2" variable_2="k2"/>
<map_variables variable_1="k7" variable_2="k7"/>
<map_variables variable_1="k7r" variable_2="k7r"/>
<map_variables variable_1="k4" variable_2="k4"/>
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<connection>
<map_components component_1="rate_constants" component_2="UbE"/>
<map_variables variable_1="UbE" variable_2="UbE"/>
<map_variables variable_1="ku" variable_2="ku"/>
<map_variables variable_1="kur" variable_2="kur"/>
<map_variables variable_1="Kmu" variable_2="Kmu"/>
<map_variables variable_1="Kmur" variable_2="Kmur"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="mass"/>
<map_variables variable_1="mu" variable_2="mu"/>
</connection>
<connection>
<map_components component_1="rate_constants" component_2="Cdc25"/>
<map_variables variable_1="Cdc25" variable_2="Cdc25"/>
<map_variables variable_1="kc" variable_2="kc"/>
<map_variables variable_1="kcr" variable_2="kcr"/>
<map_variables variable_1="Kmc" variable_2="Kmc"/>
<map_variables variable_1="Kmcr" variable_2="Kmcr"/>
</connection>
<connection>
<map_components component_1="G2K" component_2="R"/>
<map_variables variable_1="R" variable_2="R"/>
<map_variables variable_1="G2K" variable_2="G2K"/>
</connection>
<connection>
<map_components component_1="G2K" component_2="G2R"/>
<map_variables variable_1="G2R" variable_2="G2R"/>
<map_variables variable_1="G2K" variable_2="G2K"/>
</connection>
<connection>
<map_components component_1="G2K" component_2="PG2"/>
<map_variables variable_1="PG2" variable_2="PG2"/>
<map_variables variable_1="G2K" variable_2="G2K"/>
</connection>
<connection>
<map_components component_1="R" component_2="mass"/>
<map_variables variable_1="mass" variable_2="mass"/>
</connection>
<connection>
<map_components component_1="R" component_2="PG2"/>
<map_variables variable_1="PG2" variable_2="PG2"/>
<map_variables variable_1="R" variable_2="R"/>
</connection>
<connection>
<map_components component_1="R" component_2="G2R"/>
<map_variables variable_1="G2R" variable_2="G2R"/>
<map_variables variable_1="R" variable_2="R"/>
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<connection>
<map_components component_1="R" component_2="PG2R"/>
<map_variables variable_1="PG2R" variable_2="PG2R"/>
<map_variables variable_1="R" variable_2="R"/>
</connection>
<connection>
<map_components component_1="R" component_2="G1K"/>
<map_variables variable_1="G1K" variable_2="G1K"/>
<map_variables variable_1="R" variable_2="R"/>
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<connection>
<map_components component_1="R" component_2="G1R"/>
<map_variables variable_1="G1R" variable_2="G1R"/>
<map_variables variable_1="R" variable_2="R"/>
</connection>
<connection>
<map_components component_1="G1K" component_2="G1R"/>
<map_variables variable_1="G1R" variable_2="G1R"/>
<map_variables variable_1="G1K" variable_2="G1K"/>
</connection>
<connection>
<map_components component_1="PG2" component_2="PG2R"/>
<map_variables variable_1="PG2R" variable_2="PG2R"/>
<map_variables variable_1="PG2" variable_2="PG2"/>
</connection>
<connection>
<map_components component_1="UbE" component_2="IE"/>
<map_variables variable_1="IE" variable_2="IE"/>
</connection>
<connection>
<map_components component_1="Cig2_total" component_2="G1K"/>
<map_variables variable_1="G1K" variable_2="G1K"/>
</connection>
<connection>
<map_components component_1="Cig2_total" component_2="G1R"/>
<map_variables variable_1="G1R" variable_2="G1R"/>
</connection>
<connection>
<map_components component_1="Rum1_total" component_2="R"/>
<map_variables variable_1="R" variable_2="R"/>
</connection>
<connection>
<map_components component_1="Rum1_total" component_2="G1R"/>
<map_variables variable_1="G1R" variable_2="G1R"/>
</connection>
<connection>
<map_components component_1="Rum1_total" component_2="G2R"/>
<map_variables variable_1="G2R" variable_2="G2R"/>
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<connection>
<map_components component_1="Rum1_total" component_2="PG2R"/>
<map_variables variable_1="PG2R" variable_2="PG2R"/>
</connection>
<connection>
<map_components component_1="Cdc13_total" component_2="G2K"/>
<map_variables variable_1="G2K" variable_2="G2K"/>
</connection>
<connection>
<map_components component_1="Cdc13_total" component_2="G2R"/>
<map_variables variable_1="G2R" variable_2="G2R"/>
</connection>
<connection>
<map_components component_1="Cdc13_total" component_2="PG2"/>
<map_variables variable_1="PG2" variable_2="PG2"/>
</connection>
<connection>
<map_components component_1="Cdc13_total" component_2="PG2R"/>
<map_variables variable_1="PG2R" variable_2="PG2R"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Seq rdf:about="rdf:#3868e4b5-6521-4775-9f93-fc8da3f27cf8">
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<rdf:value>Initial values for the variables were added to the model. Extra variables were added to create the graphs from the research paper.
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Proceedings of the National Academy of Sciences USA</dc:title>
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<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean</vCard:Given>
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<rdf:value>added cmeta id's to several variables</rdf:value>
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<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Original CellML version of the model</dc:title>
<dc:publisher xmlns:dc="http://purl.org/dc/elements/1.1/">The University of Auckland, Auckland Bioengineering Institute</dc:publisher>
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<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean Lim</vCard:FN>
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<dc:creator xmlns:dc="http://purl.org/dc/elements/1.1/" rdf:resource="rdf:#3868e4b5-6521-4775-9f93-fc8da3f27cf8"/>
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Modeling the control of DNA replication in fission yeast</dc:title>
<bqs:volume xmlns:bqs="http://www.cellml.org/bqs/1.0#">94</bqs:volume>
<bqs:first_page xmlns:bqs="http://www.cellml.org/bqs/1.0#">9147</bqs:first_page>
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<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2003-04-22T00:00:00+00:00</dcterms:W3CDTF>
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<rdf:Description rdf:about="#PG2">
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">Cdc13-P-Cdc2 complex</dcterms:alternative>
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<rdf:Description rdf:about="#IE">
<dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">IE</dc:title>
<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">intermediary enzyme</dcterms:alternative>
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<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">Cdc13-Cdc2-Rum1 complex</dcterms:alternative>
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<rdf:value>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.</rdf:value>
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<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">Cdc13-Cdc2 complex</dcterms:alternative>
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<vCard:FN xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Catherine Lloyd</vCard:FN>
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<rdf:value>Fixed bullet points in the documentation.</rdf:value>
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<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2008-12-09T15:08:56+13:00</dcterms:W3CDTF>
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<dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">Cig2-Cdc2 complex</dcterms:alternative>
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<rdf:value>This is the CellML description of Novak and Tyson's 1997 model of the
control of DNA replication in fission yeast.</rdf:value>
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<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2009-02-18T13:53:20+13:00</dcterms:W3CDTF>
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<vCard:Given xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">Jeelean</vCard:Given>
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<dcterms:W3CDTF xmlns:dcterms="http://purl.org/dc/terms/">2007-06-15T10:32:36+12:00</dcterms:W3CDTF>
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