- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-07-09 07:57:22+12:00
- Desc:
- committing version01 of goldbeter_1991
- Permanent Source URI:
- https://models.fieldml.org/workspace/goldbeter_1991/rawfile/9dbac58786f00193d98f82f1662573d1028d1318/goldbeter_1991.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : goldbeter_model_1991.xml
CREATED : 30th April 2003
LAST MODIFIED : 30th April 2003
AUTHOR : Catherine Lloyd
Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/1/02 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Albert Goldbeter's
1991 minimal model for the mitotic oscillator invoving cyclin and cdc2 kinase.
CHANGES:
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" cmeta:id="goldbeter_1991_version01" name="goldbeter_1991_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Minimal Cascade Model for the Mitotic Oscillator Involving Cyclin and cdc2 Kinase</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Better understanding of the molecular mechanisms underlying the cell cycle has given rise to the theory that there may be one universal, homologous mechanism controlling the onset of mitosis. Studies with yeast and embryonic cells suggest that mitosis is triggered by the periodic activation of cdc2 kinase. Using this experimental data, Albert Goldbeter developed a minimal mathematical model which describes the mitotic oscillator involving cyclin and cdc2 kinase (see <xref linkend="fig_reaction_diagram"/> below). This model is based on the situation in amphibian embryos. As cyclin, a protein signalling molecule, accumulates and exceeds a certain threshold concentration, mitosis is triggered. In the first cycle of the bicyclic cascade model, cyclin promotes the activation of cdc2 kinase through reversible dephosphorylation. In the second cycle, cdc2 kinase activates a cyclin protease by reversible phosphorylation. Since cyclin activates cdc2 kinase, and in turn, active cdc2 kinase indirectly triggers the degradation of cyclin, cyclin oscillations may originate from a negative feedback loop.
</para>
<para>
Model simulations support this theory. Oscillations can arise as long as thresholds exist in the activation of cdc2 kinase by cyclin, and in the activation of cyclin protease by cdc2 kinase. Time lags associated with these thresholds, together with the delayed negative feedback from the cdc2-induced cyclin degradation, can readily lead to sustained mitotic oscillations.
</para>
<para>
Albert Goldbeter acknowledges that the model is a simplification of the biological situation, and it is based on a number of assumptions, but in its simplified form, the model highlights the conditions in which the cyclin-cdc2 kinase system can operate as an autonomous oscillator. The model is also useful in considering the mechanisms underlying the more complex situation in yeast and somatic cells. By highlighting the ways in which oscillations may be stopped, the models suggests how the products of other genes could play a role in the control of mitosis.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.pnas.org/cgi/content/abstract/88/20/9107">A minimal cascade model for the mitotic oscillator involving cyclin and cdc2 kinase</ulink>, Albert Goldbeter, 1991, <ulink url="http://www.pnas.org/">
<emphasis>Proceedings of the National Academy of Sciences</emphasis>
</ulink>, 88, 9107-9111. (A <ulink url="http://www.pnas.org/cgi/reprint/88/20/9107.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=1833774&dopt=Abstract">PubMed ID: 1833774</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>cell diagram</title>
</objectinfo>
<imagedata fileref="reaction_diagram.gif"/>
</imageobject>
</mediaobject>
<caption>Minimal cascade model for the mitotic oscillations between cyclin and cdc2 kinase (M) during the cell cycle. X represents the fraction of active (phosphorylated) cyclin protease. * represents the fraction of inactive enzymes.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!--
Below, we define some additional units for association with variables and
constants within the model.
-->
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="minute">
<unit units="second" multiplier="60.0"/>
</units>
<units name="flux">
<unit units="micromolar"/>
<unit units="minute" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="minute" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="micromolar" exponent="-1"/>
<unit units="minute" exponent="-1"/>
</units>
<component name="environment">
<variable units="minute" public_interface="out" name="time"/>
</component>
<!--
The following components describe all the reactants and products involved in
reactions.
-->
<component cmeta:id="C" name="C">
<variable units="micromolar" public_interface="out" name="C" initial_value="0.01"/>
<variable units="second_order_rate_constant" name="vi" initial_value="0.023"/>
<variable units="first_order_rate_constant" name="kd" initial_value="3.33E-3"/>
<variable units="flux" public_interface="in" name="delta_C_rxn_5"/>
<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>C</ci>
</apply>
<apply>
<plus/>
<ci>vi</ci>
<ci>delta_C_rxn_5</ci>
<apply>
<minus/>
<apply>
<times/>
<ci>kd</ci>
<ci>C</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="M_" name="M_">
<rdf:RDF>
<rdf:Description rdf:about="M_">
<dc:title>M_</dc:title>
<dcterms:alternative>
fraction of inactive cdc2 kinase
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="dimensionless" public_interface="out" name="M_" initial_value="0.99"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_M__rxn_1"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_M__rxn_2"/>
<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>M_</ci>
</apply>
<apply>
<plus/>
<ci>delta_M__rxn_1</ci>
<ci>delta_M__rxn_2</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="M" name="M">
<rdf:RDF>
<rdf:Description rdf:about="M">
<dc:title>M</dc:title>
<dcterms:alternative>
fraction of active cdc2 kinase
</dcterms:alternative>
<dcterms:alternative>E3</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="dimensionless" public_interface="out" name="M" initial_value="0.01"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_M_rxn_1"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_M_rxn_2"/>
<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>M</ci>
</apply>
<apply>
<plus/>
<ci>delta_M_rxn_1</ci>
<ci>delta_M_rxn_2</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="X_" name="X_">
<rdf:RDF>
<rdf:Description rdf:about="X_">
<dc:title>X_</dc:title>
<dcterms:alternative>
fraction of inactive cyclin protease
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="dimensionless" public_interface="out" name="X_" initial_value="0.99"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_X__rxn_3"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_X__rxn_4"/>
<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>X_</ci>
</apply>
<apply>
<plus/>
<ci>delta_X__rxn_3</ci>
<ci>delta_X__rxn_4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="X" name="X">
<rdf:RDF>
<rdf:Description rdf:about="X">
<dc:title>X</dc:title>
<dcterms:alternative>
fraction of active cyclin protease
</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="dimensionless" public_interface="out" name="X" initial_value="0.01"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_X_rxn_3"/>
<variable units="first_order_rate_constant" public_interface="in" name="delta_X_rxn_4"/>
<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>X</ci>
</apply>
<apply>
<plus/>
<ci>delta_X_rxn_3</ci>
<ci>delta_X_rxn_4</ci>
</apply>
</apply>
</math>
</component>
<!--
The following components describe all the enzymes involved in reactions
-->
<component cmeta:id="E1" name="E1">
<variable units="micromolar" public_interface="out" name="E1"/>
</component>
<component cmeta:id="E2" name="E2">
<variable units="micromolar" public_interface="out" name="E2"/>
</component>
<component cmeta:id="E4" name="E4">
<variable units="micromolar" public_interface="out" name="E4"/>
</component>
<!--
The following components describe the reactions of the model.
-->
<component name="reaction1">
<variable units="dimensionless" public_interface="in" name="M_"/>
<variable units="dimensionless" public_interface="in" name="M"/>
<variable units="micromolar" public_interface="in" name="C"/>
<variable units="micromolar" public_interface="in" name="E1"/>
<variable units="first_order_rate_constant" name="V1"/>
<variable units="first_order_rate_constant" name="VM1" initial_value="0.5"/>
<variable units="micromolar" name="K1" initial_value="0.1"/>
<variable units="micromolar" name="Kc" initial_value="0.3"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_M__rxn_1"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_M_rxn_1"/>
<variable units="flux" name="r"/>
<reaction reversible="no">
<variable_ref variable="M_">
<role stoichiometry="1" direction="forward" delta_variable="delta_M__rxn_1" role="reactant"/>
</variable_ref>
<variable_ref variable="M">
<role stoichiometry="1" direction="forward" delta_variable="delta_M_rxn_1" role="product"/>
</variable_ref>
<variable_ref variable="C">
<role role="activator"/>
</variable_ref>
<variable_ref variable="E1">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<times/>
<ci> V1 </ci>
<apply>
<divide/>
<ci> M_ </ci>
<apply>
<plus/>
<ci> K1 </ci>
<ci> M_ </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V1_calculation">
<eq/>
<ci> V1 </ci>
<apply>
<times/>
<ci> VM1 </ci>
<apply>
<divide/>
<ci> C </ci>
<apply>
<plus/>
<ci> Kc </ci>
<ci> C </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component name="reaction2">
<variable units="dimensionless" public_interface="in" name="M_"/>
<variable units="dimensionless" public_interface="in" name="M"/>
<variable units="first_order_rate_constant" name="V2" initial_value="0.167"/>
<variable units="micromolar" name="K2" initial_value="0.1"/>
<variable units="micromolar" public_interface="in" name="E2"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_M__rxn_2"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_M_rxn_2"/>
<variable units="flux" name="r"/>
<reaction reversible="no">
<variable_ref variable="M">
<role stoichiometry="1" direction="forward" delta_variable="delta_M_rxn_2" role="reactant"/>
</variable_ref>
<variable_ref variable="M_">
<role stoichiometry="1" direction="forward" delta_variable="delta_M__rxn_2" role="product"/>
</variable_ref>
<variable_ref variable="E2">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<times/>
<ci> V2 </ci>
<apply>
<divide/>
<ci> M </ci>
<apply>
<plus/>
<ci> K2 </ci>
<ci> M </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="dimensionless" public_interface="in" name="X_"/>
<variable units="dimensionless" public_interface="in" name="X"/>
<variable units="dimensionless" public_interface="in" name="M"/>
<variable units="first_order_rate_constant" name="V3"/>
<variable units="first_order_rate_constant" name="VM3" initial_value="0.2"/>
<variable units="micromolar" name="K3" initial_value="0.1"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_X__rxn_3"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_X_rxn_3"/>
<variable units="flux" name="r"/>
<reaction reversible="no">
<variable_ref variable="X_">
<role stoichiometry="1" direction="forward" delta_variable="delta_X__rxn_3" role="reactant"/>
</variable_ref>
<variable_ref variable="X">
<role stoichiometry="1" direction="forward" delta_variable="delta_X_rxn_3" role="product"/>
</variable_ref>
<variable_ref variable="M">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<times/>
<ci> V3 </ci>
<apply>
<divide/>
<ci> X_ </ci>
<apply>
<plus/>
<ci> K3 </ci>
<ci> X_ </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="V3_calculation">
<eq/>
<ci> V3 </ci>
<apply>
<times/>
<ci> M </ci>
<ci> VM3 </ci>
</apply>
</apply>
</math>
</component>
<component name="reaction4">
<variable units="dimensionless" public_interface="in" name="X_"/>
<variable units="dimensionless" public_interface="in" name="X"/>
<variable units="first_order_rate_constant" name="V4" initial_value="0.1"/>
<variable units="micromolar" name="K4" initial_value="0.1"/>
<variable units="micromolar" public_interface="in" name="E4"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_X__rxn_4"/>
<variable units="first_order_rate_constant" public_interface="out" name="delta_X_rxn_4"/>
<variable units="flux" name="r"/>
<reaction reversible="no">
<variable_ref variable="X">
<role stoichiometry="1" direction="forward" delta_variable="delta_X_rxn_4" role="reactant"/>
</variable_ref>
<variable_ref variable="X_">
<role stoichiometry="1" direction="forward" delta_variable="delta_X__rxn_4" role="product"/>
</variable_ref>
<variable_ref variable="E4">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<times/>
<ci> V4 </ci>
<apply>
<divide/>
<ci> X </ci>
<apply>
<plus/>
<ci> K4 </ci>
<ci> X </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction5">
<variable units="micromolar" public_interface="in" name="C"/>
<variable units="dimensionless" public_interface="in" name="X"/>
<variable units="second_order_rate_constant" name="vd" initial_value="0.1"/>
<variable units="micromolar" name="Kd" initial_value="0.02"/>
<variable units="flux" public_interface="out" name="delta_C_rxn_5"/>
<variable units="flux" name="r"/>
<reaction reversible="no">
<variable_ref variable="C">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_rxn_5" role="reactant"/>
</variable_ref>
<variable_ref variable="X">
<role role="catalyst"/>
</variable_ref>
<variable_ref variable="r">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> r </ci>
<apply>
<times/>
<ci> vd </ci>
<ci> X </ci>
<apply>
<divide/>
<ci> C </ci>
<apply>
<plus/>
<ci> Kd </ci>
<ci> C </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="environment" component_1="C"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="M"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="M_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="X"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="X_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="C"/>
<map_variables variable_2="C" variable_1="C"/>
<map_variables variable_2="delta_C_rxn_5" variable_1="delta_C_rxn_5"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="E1"/>
<map_variables variable_2="E1" variable_1="E1"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="C"/>
<map_variables variable_2="C" variable_1="C"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="M"/>
<map_variables variable_2="M" variable_1="M"/>
<map_variables variable_2="delta_M_rxn_1" variable_1="delta_M_rxn_1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="M"/>
<map_variables variable_2="M" variable_1="M"/>
<map_variables variable_2="delta_M_rxn_2" variable_1="delta_M_rxn_2"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="E2"/>
<map_variables variable_2="E2" variable_1="E2"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="M"/>
<map_variables variable_2="M" variable_1="M"/>
</connection>
<connection>
<map_components component_2="reaction1" component_1="M_"/>
<map_variables variable_2="M_" variable_1="M_"/>
<map_variables variable_2="delta_M__rxn_1" variable_1="delta_M__rxn_1"/>
</connection>
<connection>
<map_components component_2="reaction2" component_1="M_"/>
<map_variables variable_2="M_" variable_1="M_"/>
<map_variables variable_2="delta_M__rxn_2" variable_1="delta_M__rxn_2"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="X"/>
<map_variables variable_2="X" variable_1="X"/>
<map_variables variable_2="delta_X_rxn_3" variable_1="delta_X_rxn_3"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="X"/>
<map_variables variable_2="X" variable_1="X"/>
<map_variables variable_2="delta_X_rxn_4" variable_1="delta_X_rxn_4"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="E4"/>
<map_variables variable_2="E4" variable_1="E4"/>
</connection>
<connection>
<map_components component_2="reaction5" component_1="X"/>
<map_variables variable_2="X" variable_1="X"/>
</connection>
<connection>
<map_components component_2="reaction3" component_1="X_"/>
<map_variables variable_2="X_" variable_1="X_"/>
<map_variables variable_2="delta_X__rxn_3" variable_1="delta_X__rxn_3"/>
</connection>
<connection>
<map_components component_2="reaction4" component_1="X_"/>
<map_variables variable_2="X_" variable_1="X_"/>
<map_variables variable_2="delta_X__rxn_4" variable_1="delta_X__rxn_4"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="rdf:#4578d0b8-4edb-40ec-91b4-4e28cba27e8e">
<vCard:N rdf:resource="rdf:#12ed0ba9-b87c-48d0-af9c-a5620e3d940c"/>
</rdf:Description>
<rdf:Description rdf:about="#C">
<dcterms:alternative>cyclin concentration</dcterms:alternative>
<dc:title>C</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#aad8defa-a4ba-4913-9fd2-feadc3634db3">
<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="#goldbeter_1991_version01">
<dc:title>
Albert Goldbeter's 1991 minimal model for the mitotic oscillator
invoving cyclin and cdc2 kinase.
</dc:title>
<cmeta:comment rdf:resource="rdf:#39f3b591-3df3-4def-8ed6-1172f9ce069d"/>
<bqs:reference rdf:resource="rdf:#f6d898d4-f7c0-47f7-b7cd-f4ebb524ebd0"/>
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</rdf:Description>
<rdf:Description rdf:about="rdf:#39f3b591-3df3-4def-8ed6-1172f9ce069d">
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<rdf:value>
This is the CellML description of Albert Goldbeter's 1991 minimal
model for the mitotic oscillator invoving cyclin and cdc2 kinase.
</rdf:value>
</rdf:Description>
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<dc:creator rdf:resource="rdf:#acac69a2-dfc4-4144-a2f8-f6240d039487"/>
<dc:title>
A Minimal Cascade Model for the Mitotic Oscillator Involving Cyclin
and cdc2 Kinase
</dc:title>
<bqs:volume>88</bqs:volume>
<bqs:first_page>9107</bqs:first_page>
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<dcterms:issued rdf:resource="rdf:#763960c2-f86b-4522-872a-d9277723e8cb"/>
<bqs:last_page>9111</bqs:last_page>
</rdf:Description>
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<vCard:Given>Albert</vCard:Given>
<vCard:Family>Goldbeter</vCard:Family>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
<dcterms:created rdf:resource="rdf:#56f12621-4ee0-461f-9fab-9ff92c2ae096"/>
<dc:creator rdf:resource="rdf:#f2157318-80a7-4632-91ce-7c741b1d71e3"/>
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<vCard:N rdf:resource="rdf:#9da48ac0-d669-408e-bb82-138a3a658ad5"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e5d42629-6c91-4500-914b-39108cc4f2a1">
<dc:title>
Proceedings of the National Academy of Sciences USA
</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#54f1a505-33fd-4aca-9100-cd82596afeed">
<bqs:Pubmed_id>1833774</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#25bd5e89-710a-449c-a019-46f2c01f11c6"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#032919ef-0abf-43a5-8061-6c7e9f789660">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="#E2">
<dcterms:alternative>kinase</dcterms:alternative>
<dc:title>E2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E1">
<dcterms:alternative>phosphatase</dcterms:alternative>
<dc:title>E1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#98a80071-af73-423c-94a1-b9f866a7a195">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>cell cycle</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#E4">
<dcterms:alternative>phosphatase</dcterms:alternative>
<dc:title>E4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#acac69a2-dfc4-4144-a2f8-f6240d039487">
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<rdf:Description rdf:about="rdf:#bc72216f-699b-4b53-a331-8780130fbbdf">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f6d898d4-f7c0-47f7-b7cd-f4ebb524ebd0">
<dc:subject rdf:resource="rdf:#98a80071-af73-423c-94a1-b9f866a7a195"/>
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<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#56f12621-4ee0-461f-9fab-9ff92c2ae096">
<dcterms:W3CDTF>2003-04-30</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#763960c2-f86b-4522-872a-d9277723e8cb">
<dcterms:W3CDTF>1991-10</dcterms:W3CDTF>
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</rdf:RDF>
</model>
