- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2006-07-09 07:16:14+12:00
- Desc:
- committing version01 of asthagiri_lauffenburger_2001
- Permanent Source URI:
- https://models.cellml.org/workspace/asthagiri_lauffenburger_2001/rawfile/aab8fd37da8ecd9b415df58e9011782a05d15cd5/asthagiri_lauffenburger_2001.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : MAPK_cascade_2001.xml
CREATED : 25th October 2001
LAST MODIFIED : 26th April 2005
AUTHOR : Catherine Lloyd
Department of Engineering Science
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification .
DESCRIPTION : This file contains a CellML description of a study by Asthagiri
and Lauffenburger (2001) of the feedback effects on signal dynamics in the
mitogen-activated protein kinase (MAPK) cascade.
CHANGES:
22/01/2002 - AAC - Updated metadata to conform to the 16/1/02 CellML Metadata
1.0 Specification.
25/02/2002 - CML - Altered connections after checking the model with the
validator.
18/07/2002 - CML - Added more metadata.
27/08/2002 - AAC - Corrected the initial value of variable 'k6_' in component
'adaptor_heterodimer_syn'.
09/04/2003 - AAC - Added publication date information.
26/04/2005 - PJV - Changed unit dimensions to make them consistent
--><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="asthagiri_lauffenburger_2001_version01" name="asthagiri_lauffenburger_2001_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Feedback Effects On Signal Dynamics In A Mitogen-Activated Protein Kinase (MAPK) Cascade</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>
In 2001, Anand Asthagiri and Douglas Lauffenburger published a mathematical model which examined the mechanisms that govern MAPK pathway dynamics (see <xref linkend="fig_pathway_diagram"/> below). Their model builds upon the MAPK cascade model of Chi-Ying Huang and James Ferrell (1996). This earlier model focused on the steady-state effects of signaling, whereas more recently, it has been discovered that a signal's information content partly resides in its dynamics.
</para>
<para>
In their model, Anand Asthagiri and Douglas Lauffenburger concentrate on the role of negative feedback mechanisms in the generation of signal adaptation - a term referring to the reset of a signal to prestimulation levels. They assess how different modes of feedback affect the properties of MAPK signalling dynamics.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://pubs.acs.org/cgi-bin/abstract.cgi/bipret/2001/17/i02/abs/bp010009k.html">A Computational Study of Feedback Effects on Signal Dynamics in a Mitogen-Activated Protein Kinase (MAPK) Pathway Model</ulink>, Anand R. Asthagiri and Douglas A. Lauffenburger, 2001, <ulink url="http://pubs.acs.org/journals/bipret/index.html">
<emphasis>Biotechnol. Prog</emphasis>
</ulink>, 17, 227-239. (<ulink url="http://pubs.acs.org/cgi-bin/article.cgi/bipret/2001/17/i02/html/bp010009k.html">Full text</ulink> and PDF versions are available to subscribers on the ACS Publications website. <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=11312698&dopt=Abstract">PubMed ID: 11312698</ulink>
</para>
<para>
The raw CellML description of the MAPK cascade model with feedback effects can be downloaded in various formats as described in <xref linkend="sec_download_this_model"/>. For an example of a more complete documentation of another real reaction pathway, see <ulink url="${HTML_EXMPL_BI_EGF_INTRO}">The Bhalla Iyengar EGF Pathway Model, 1999</ulink>.
</para>
<informalfigure float="0" id="fig_pathway_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>the conventional rendering of the MAPK cascade with feedback effects</title>
</objectinfo>
<imagedata fileref="conventional_rendering.gif"/>
</imageobject>
</mediaobject>
<caption>A rendering of the MAPK cascade with feedback effects. Species are represented by rounded rectangles, and reactions by arrows. The action of a catalyst on a reaction is represented by dashed lines.</caption>
</informalfigure>
<para>
In CellML, models are thought of as connected networks of discrete components. These components may correspond to physiologically separated regions or chemically distinct objects, or may be useful modelling abstractions. This model has 71 components representing chemically distinct objects (41 chemical species and 30 reactions) and one component defined for modelling convenience which stores the universal variable time. Because this model has so many components, its CellML rendering would be complex. For an example of a CellML rendering of a reaction pathway see <ulink url="${HTML_EXMPL_BI_EGF_INTRO}">The Bhalla Iyengar EGF Pathway Model, 1999</ulink>.
</para>
</sect1>
</article>
</documentation>
<!--
Below, we define some additional units for association with variables and
constants within the model. The identifiers are fairly self-explanatory.
-->
<units name="minute">
<unit units="second" multiplier="60.0"/>
</units>
<units base_units="yes" name="number"/>
<units base_units="yes" name="cell"/>
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</units>
<units name="molar">
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<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
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<unit units="minute" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
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</units>
<units name="second_order_rate_constant">
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<unit units="minute" exponent="-1"/>
</units>
<component name="global_variables">
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</component>
<component cmeta:id="R" name="R">
<variable units="number_per_cell" public_interface="out" name="R" initial_value="1.0"/>
<variable units="number_per_cell_per_minute" public_interface="in" name="delta_R_ligand_receptor_binding"/>
<variable units="minute" public_interface="in" name="time"/>
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<ci>delta_C__receptor_adaptors_complex_syn2</ci>
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<variable units="flux" public_interface="in" name="delta_L_ligand_receptor_binding"/>
<variable units="minute" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
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<diff/>
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</apply>
</math>
</component>
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<variable units="molar" public_interface="out" name="A2_"/>
<variable units="flux" public_interface="in" name="delta_A2__E0_E4__desyn"/>
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<apply>
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<variable units="flux" public_interface="in" name="delta_E4__E5_activation"/>
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<ci>delta_E4__E2_E4__desyn</ci>
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<ci>delta_E4__E5_activation</ci>
<ci>delta_E4__E0_E4__syn</ci>
<ci>delta_E4__E2_E4__syn</ci>
<ci>delta_E4__E4__P4_binding</ci>
<ci>delta_E4__E4__E5_binding</ci>
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<component cmeta:id="E1_" name="E1_">
<variable units="molar" public_interface="out" name="E1_"/>
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<variable units="flux" public_interface="in" name="delta_E1__E2_activation"/>
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<variable units="minute" public_interface="in" name="time"/>
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<variable units="molar" public_interface="out" name="E3_"/>
<variable units="flux" public_interface="in" name="delta_E3__E3_activation"/>
<variable units="flux" public_interface="in" name="delta_E3__E4_activation"/>
<variable units="flux" public_interface="in" name="delta_E3__E3_P3_binding"/>
<variable units="flux" public_interface="in" name="delta_E3__E3__E4_binding"/>
<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>E3_</ci>
</apply>
<apply>
<plus/>
<ci>delta_E3__E3_activation</ci>
<ci>delta_E3__E4_activation</ci>
<ci>delta_E3__E3_P3_binding</ci>
<ci>delta_E3__E3__E4_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E3" name="E3">
<variable units="molar" public_interface="out" name="E3" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_E3_E3__inactivation"/>
<variable units="flux" public_interface="in" name="delta_E3_E2__E3_binding"/>
<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>E3</ci>
</apply>
<apply>
<plus/>
<ci>delta_E3_E3__inactivation</ci>
<ci>delta_E3_E2__E3_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E3_P3" name="E3_P3">
<variable units="molar" public_interface="out" name="E3_P3"/>
<variable units="flux" public_interface="in" name="delta_E3_P3_E3_P3_binding"/>
<variable units="flux" public_interface="in" name="delta_E3_P3_E3__inactivation"/>
<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>E3_P3</ci>
</apply>
<apply>
<plus/>
<ci>delta_E3_P3_E3_P3_binding</ci>
<ci>delta_E3_P3_E3__inactivation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="P3" name="P3">
<variable units="molar" public_interface="out" name="P3" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_P3_E3__inactivation"/>
<variable units="flux" public_interface="in" name="delta_P3_E3_P3_binding"/>
<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>P3</ci>
</apply>
<apply>
<plus/>
<ci>delta_P3_E3__inactivation</ci>
<ci>delta_P3_E3_P3_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E4" name="E4">
<variable units="molar" public_interface="out" name="E4" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_E4_E4__inactivation"/>
<variable units="flux" public_interface="in" name="delta_E4_E3__E4_binding"/>
<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>E4</ci>
</apply>
<apply>
<plus/>
<ci>delta_E4_E4__inactivation</ci>
<ci>delta_E4_E3__E4_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E4_P4" name="E4_P4">
<variable units="molar" public_interface="out" name="E4_P4"/>
<variable units="flux" public_interface="in" name="delta_E4_P4_E4__P4_binding"/>
<variable units="flux" public_interface="in" name="delta_E4_P4_E4__inactivation"/>
<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>E4_P4</ci>
</apply>
<apply>
<plus/>
<ci>delta_E4_P4_E4__P4_binding</ci>
<ci>delta_E4_P4_E4__inactivation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="P4" name="P4">
<variable units="molar" public_interface="out" name="P4" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_P4_E4__inactivation"/>
<variable units="flux" public_interface="in" name="delta_P4_E4__P4_binding"/>
<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>P4</ci>
</apply>
<apply>
<plus/>
<ci>delta_P4_E4__inactivation</ci>
<ci>delta_P4_E4__P4_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E5_" name="E5_">
<variable units="molar" public_interface="out" name="E5_"/>
<variable units="flux" public_interface="in" name="delta_E5__E5_activation"/>
<variable units="flux" public_interface="in" name="delta_E5__E5__P5_binding"/>
<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>E5_</ci>
</apply>
<apply>
<plus/>
<ci>delta_E5__E5_activation</ci>
<ci>delta_E5__E5__P5_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E5" name="E5">
<variable units="molar" public_interface="out" name="E5" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_E5_E5__inactivation"/>
<variable units="flux" public_interface="in" name="delta_E5_E4__E5_binding"/>
<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>E5</ci>
</apply>
<apply>
<plus/>
<ci>delta_E5_E5__inactivation</ci>
<ci>delta_E5_E4__E5_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="P5" name="P5">
<variable units="molar" public_interface="out" name="P5" initial_value="1.0"/>
<variable units="flux" public_interface="in" name="delta_P5_E5__inactivation"/>
<variable units="flux" public_interface="in" name="delta_P5_E5__P5_binding"/>
<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>P5</ci>
</apply>
<apply>
<plus/>
<ci>delta_P5_E5__inactivation</ci>
<ci>delta_P5_E5__P5_binding</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E5_P5" name="E5_P5">
<variable units="molar" public_interface="out" name="E5_P5"/>
<variable units="flux" public_interface="in" name="delta_E5_P5_E5__P5_binding"/>
<variable units="flux" public_interface="in" name="delta_E5_P5_E5__inactivation"/>
<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>E5_P5</ci>
</apply>
<apply>
<plus/>
<ci>delta_E5_P5_E5__P5_binding</ci>
<ci>delta_E5_P5_E5__inactivation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="A1A2" name="A1A2">
<variable units="molar" public_interface="out" name="A1A2"/>
<variable units="flux" public_interface="in" name="delta_A1A2_receptor_adaptors_complex_syn2"/>
<variable units="flux" public_interface="in" name="delta_A1A2_adaptor_heterodimer_syn"/>
<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>A1A2</ci>
</apply>
<apply>
<plus/>
<ci>delta_A1A2_receptor_adaptors_complex_syn2</ci>
<ci>delta_A1A2_adaptor_heterodimer_syn</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E2_E4_" name="E2_E4_">
<variable units="molar" public_interface="out" name="E2_E4_"/>
<variable units="flux" public_interface="in" name="delta_E2_E4__E2_E4__syn"/>
<variable units="flux" public_interface="in" name="delta_E2_E4__E2_E4__desyn"/>
<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>E2_E4_</ci>
</apply>
<apply>
<plus/>
<ci>delta_E2_E4__E2_E4__syn</ci>
<ci>delta_E2_E4__E2_E4__desyn</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E0_E1" name="E0_E1">
<variable units="molar" public_interface="out" name="E0_E1"/>
<variable units="flux" public_interface="in" name="delta_E0_E1_E0__E1_binding"/>
<variable units="flux" public_interface="in" name="delta_E0_E1_E1_activation"/>
<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>E0_E1</ci>
</apply>
<apply>
<plus/>
<ci>delta_E0_E1_E0__E1_binding</ci>
<ci>delta_E0_E1_E1_activation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E1_E2" name="E1_E2">
<variable units="molar" public_interface="out" name="E1_E2"/>
<variable units="flux" public_interface="in" name="delta_E1_E2_E1__E2_binding"/>
<variable units="flux" public_interface="in" name="delta_E1_E2_E2_activation"/>
<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>E1_E2</ci>
</apply>
<apply>
<plus/>
<ci>delta_E1_E2_E1__E2_binding</ci>
<ci>delta_E1_E2_E2_activation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E2_E3" name="E2_E3">
<variable units="molar" public_interface="out" name="E2_E3"/>
<variable units="flux" public_interface="in" name="delta_E2_E3_E2__E3_binding"/>
<variable units="flux" public_interface="in" name="delta_E2_E3_E3_activation"/>
<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>E2_E3</ci>
</apply>
<apply>
<plus/>
<ci>delta_E2_E3_E2__E3_binding</ci>
<ci>delta_E2_E3_E3_activation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E3_E4" name="E3_E4">
<variable units="molar" public_interface="out" name="E3_E4"/>
<variable units="flux" public_interface="in" name="delta_E3_E4_E3__E4_binding"/>
<variable units="flux" public_interface="in" name="delta_E3_E4_E4_activation"/>
<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>E3_E4</ci>
</apply>
<apply>
<plus/>
<ci>delta_E3_E4_E3__E4_binding</ci>
<ci>delta_E3_E4_E4_activation</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E4_E5" name="E4_E5">
<variable units="molar" public_interface="out" name="E4_E5"/>
<variable units="flux" public_interface="in" name="delta_E4_E5_E4__E5_binding"/>
<variable units="flux" public_interface="in" name="delta_E4_E5_E5_activation"/>
<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>E4_E5</ci>
</apply>
<apply>
<plus/>
<ci>delta_E4_E5_E4__E5_binding</ci>
<ci>delta_E4_E5_E5_activation</ci>
</apply>
</apply>
</math>
</component>
<component name="ligand_receptor_binding">
<variable units="molar" public_interface="in" name="L"/>
<variable units="number_per_cell" public_interface="in" name="R"/>
<variable units="molar" public_interface="in" name="C"/>
<variable units="flux" public_interface="out" name="delta_L_ligand_receptor_binding"/>
<variable units="number_per_cell_per_minute" public_interface="out" name="delta_R_ligand_receptor_binding"/>
<variable units="flux" public_interface="out" name="delta_C_ligand_receptor_binding"/>
<variable units="second_order_rate_constant" name="k_forward" initial_value="1.0E7"/>
<variable units="first_order_rate_constant" name="k_reverse" initial_value="0.3"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="L">
<role stoichiometry="1" direction="forward" delta_variable="delta_L_ligand_receptor_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="R">
<role stoichiometry="1" direction="forward" delta_variable="delta_R_ligand_receptor_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="C">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_ligand_receptor_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k_forward</ci>
<ci>L</ci>
<ci>R</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k_reverse</ci>
<ci>C</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="receptor_dimerisation">
<variable units="molar" public_interface="in" name="C"/>
<variable units="molar" public_interface="in" name="C2"/>
<variable units="flux" public_interface="out" name="delta_C_receptor_dimerisation"/>
<variable units="flux" public_interface="out" name="delta_C2_receptor_dimerisation"/>
<variable units="second_order_rate_constant" name="k1" initial_value="60000000.0"/>
<variable units="first_order_rate_constant" name="k1_" initial_value="60.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="C">
<role stoichiometry="2" direction="forward" delta_variable="delta_C_receptor_dimerisation" role="reactant"/>
</variable_ref>
<variable_ref variable="C2">
<role stoichiometry="1" direction="forward" delta_variable="delta_C2_receptor_dimerisation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k1</ci>
<apply>
<power/>
<ci>C</ci>
<cn cellml:units="flux">2.0</cn>
</apply>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k1_</ci>
<ci>C2</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="dimerised_receptor_activation">
<variable units="molar" public_interface="in" name="C2"/>
<variable units="molar" public_interface="in" name="C_"/>
<variable units="flux" public_interface="out" name="delta_C2_dimerised_receptor_activation"/>
<variable units="flux" public_interface="out" name="delta_C__dimerised_receptor_activation"/>
<variable units="first_order_rate_constant" name="k2" initial_value="50.0"/>
<variable units="first_order_rate_constant" name="k2_" initial_value="5.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="C2">
<role stoichiometry="1" direction="forward" delta_variable="delta_C2_dimerised_receptor_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="C_">
<role stoichiometry="1" direction="forward" delta_variable="delta_C__dimerised_receptor_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>C2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>C_</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="receptor_adaptor_complex_syn">
<variable units="molar" public_interface="in" name="C_"/>
<variable units="molar" public_interface="in" name="A1"/>
<variable units="molar" public_interface="in" name="C_A1"/>
<variable units="flux" public_interface="out" name="delta_C__receptor_adaptor_complex_syn"/>
<variable units="flux" public_interface="out" name="delta_A1_receptor_adaptor_complex_syn"/>
<variable units="flux" public_interface="out" name="delta_C_A1_receptor_adaptor_complex_syn"/>
<variable units="second_order_rate_constant" name="k3" initial_value="300000000.0"/>
<variable units="first_order_rate_constant" name="k3_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="C_">
<role stoichiometry="1" direction="forward" delta_variable="delta_C__receptor_adaptor_complex_syn" role="reactant"/>
</variable_ref>
<variable_ref variable="A1">
<role stoichiometry="1" direction="forward" delta_variable="delta_A1_receptor_adaptor_complex_syn" role="reactant"/>
</variable_ref>
<variable_ref variable="C_A1">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_A1_receptor_adaptor_complex_syn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k3</ci>
<ci>C_</ci>
<ci>A1</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k3_</ci>
<ci>C_A1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="receptor_adaptors_complex_syn1">
<variable units="molar" public_interface="in" name="A2"/>
<variable units="molar" public_interface="in" name="C_A1"/>
<variable units="molar" public_interface="in" name="E0_"/>
<variable units="flux" public_interface="out" name="delta_A2_receptor_adaptors_complex_syn1"/>
<variable units="flux" public_interface="out" name="delta_C_A1_receptor_adaptors_complex_syn1"/>
<variable units="flux" public_interface="out" name="delta_E0__receptor_adaptors_complex_syn1"/>
<variable units="second_order_rate_constant" name="k4" initial_value="300000000.0"/>
<variable units="first_order_rate_constant" name="k4_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="A2">
<role stoichiometry="1" direction="forward" delta_variable="delta_A2_receptor_adaptors_complex_syn1" role="reactant"/>
</variable_ref>
<variable_ref variable="C_A1">
<role stoichiometry="1" direction="forward" delta_variable="delta_C_A1_receptor_adaptors_complex_syn1" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0__receptor_adaptors_complex_syn1" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k4</ci>
<ci>A2</ci>
<ci>C_A1</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k4_</ci>
<ci>E0_</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="receptor_adaptors_complex_syn2">
<variable units="molar" public_interface="in" name="C_"/>
<variable units="molar" public_interface="in" name="A1A2"/>
<variable units="molar" public_interface="in" name="E0_"/>
<variable units="flux" public_interface="out" name="delta_C__receptor_adaptors_complex_syn2"/>
<variable units="flux" public_interface="out" name="delta_A1A2_receptor_adaptors_complex_syn2"/>
<variable units="flux" public_interface="out" name="delta_E0__receptor_adaptors_complex_syn2"/>
<variable units="second_order_rate_constant" name="k5" initial_value="300000000.0"/>
<variable units="first_order_rate_constant" name="k5_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="C_">
<role stoichiometry="1" direction="forward" delta_variable="delta_C__receptor_adaptors_complex_syn2" role="reactant"/>
</variable_ref>
<variable_ref variable="A1A2">
<role stoichiometry="1" direction="forward" delta_variable="delta_A1A2_receptor_adaptors_complex_syn2" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0__receptor_adaptors_complex_syn2" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k5</ci>
<ci>C_</ci>
<ci>A1A2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k5_</ci>
<ci>E0_</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="adaptor_heterodimer_syn">
<variable units="molar" public_interface="in" name="A1A2"/>
<variable units="molar" public_interface="in" name="A1"/>
<variable units="molar" public_interface="in" name="A2"/>
<variable units="flux" public_interface="out" name="delta_A1A2_adaptor_heterodimer_syn"/>
<variable units="flux" public_interface="out" name="delta_A1_adaptor_heterodimer_syn"/>
<variable units="flux" public_interface="out" name="delta_A2_adaptor_heterodimer_syn"/>
<variable units="second_order_rate_constant" name="k6" initial_value="300000000.0"/>
<variable units="first_order_rate_constant" name="k6_" initial_value="0.000006"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="A1A2">
<role stoichiometry="1" direction="forward" delta_variable="delta_A1A2_adaptor_heterodimer_syn" role="reactant"/>
</variable_ref>
<variable_ref variable="A1">
<role stoichiometry="1" direction="forward" delta_variable="delta_A1_adaptor_heterodimer_syn" role="product"/>
</variable_ref>
<variable_ref variable="A2">
<role stoichiometry="1" direction="forward" delta_variable="delta_A2_adaptor_heterodimer_syn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k6</ci>
<ci>A1A2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k6_</ci>
<ci>A1</ci>
<ci>A2</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E0_E4__syn">
<variable units="molar" public_interface="in" name="E0_"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="molar" public_interface="in" name="E0_E4_"/>
<variable units="flux" public_interface="out" name="delta_E0__E0_E4__syn"/>
<variable units="flux" public_interface="out" name="delta_E4__E0_E4__syn"/>
<variable units="flux" public_interface="out" name="delta_E0_E4__E0_E4__syn"/>
<variable units="second_order_rate_constant" name="k7" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k7_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E0_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0__E0_E4__syn" role="reactant"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4__E0_E4__syn" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0_E4__E0_E4__syn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k7</ci>
<ci>E0_</ci>
<ci>E4_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k7_</ci>
<ci>E0_E4_</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E0_E4__desyn">
<variable units="molar" public_interface="in" name="E0_E4_"/>
<variable units="molar" public_interface="in" name="C_A1"/>
<variable units="molar" public_interface="in" name="A2_"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="flux" public_interface="out" name="delta_E0_E4__E0_E4__desyn"/>
<variable units="flux" public_interface="out" name="delta_C_A1_E0_E4__desyn"/>
<variable units="flux" public_interface="out" name="delta_A2__E0_E4__desyn"/>
<variable units="flux" public_interface="out" name="delta_E4__E0_E4__desyn"/>
<variable units="first_order_rate_constant" name="k8" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E0_E4_">
<role stoichiometry="1" delta_variable="delta_E0_E4__E0_E4__desyn" role="reactant"/>
</variable_ref>
<variable_ref variable="C_A1">
<role stoichiometry="1" delta_variable="delta_C_A1_E0_E4__desyn" role="product"/>
</variable_ref>
<variable_ref variable="A2_">
<role stoichiometry="1" delta_variable="delta_A2__E0_E4__desyn" role="product"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" delta_variable="delta_E4__E0_E4__desyn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k8</ci>
<ci>E0_E4_</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E1__P1_binding">
<variable units="molar" public_interface="in" name="P1"/>
<variable units="molar" public_interface="in" name="E1_"/>
<variable units="molar" public_interface="in" name="E1_P1"/>
<variable units="flux" public_interface="out" name="delta_P1_E1__P1_binding"/>
<variable units="flux" public_interface="out" name="delta_E1__E1__P1_binding"/>
<variable units="flux" public_interface="out" name="delta_E1_P1_E1__P1_binding"/>
<variable units="second_order_rate_constant" name="k9" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k9_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="P1">
<role stoichiometry="1" direction="forward" delta_variable="delta_P1_E1__P1_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E1_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E1__E1__P1_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E1_P1">
<role stoichiometry="1" direction="forward" delta_variable="delta_E1_P1_E1__P1_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k9</ci>
<ci>P1</ci>
<ci>E1_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k9_</ci>
<ci>E1_P1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E1__inactivation">
<variable units="molar" public_interface="in" name="E1_P1"/>
<variable units="molar" public_interface="in" name="P1"/>
<variable units="molar" public_interface="in" name="E1"/>
<variable units="flux" public_interface="out" name="delta_E1_P1_E1__inactivation"/>
<variable units="flux" public_interface="out" name="delta_P1_E1__inactivation"/>
<variable units="flux" public_interface="out" name="delta_E1_E1__inactivation"/>
<variable units="first_order_rate_constant" name="k10" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E1_P1">
<role stoichiometry="1" delta_variable="delta_E1_P1_E1__inactivation" role="reactant"/>
</variable_ref>
<variable_ref variable="P1">
<role stoichiometry="1" delta_variable="delta_P1_E1__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="E1">
<role stoichiometry="1" delta_variable="delta_E1_E1__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k10</ci>
<ci>E1_P1</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2__inactivation">
<variable units="molar" public_interface="in" name="E2_P2"/>
<variable units="molar" public_interface="in" name="E2"/>
<variable units="molar" public_interface="in" name="P2"/>
<variable units="flux" public_interface="out" name="delta_E2_P2_E2__inactivation"/>
<variable units="flux" public_interface="out" name="delta_E2_E2__inactivation"/>
<variable units="flux" public_interface="out" name="delta_P2_E2__inactivation"/>
<variable units="first_order_rate_constant" name="k11" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E2_P2">
<role stoichiometry="1" delta_variable="delta_E2_P2_E2__inactivation" role="reactant"/>
</variable_ref>
<variable_ref variable="E2">
<role stoichiometry="1" delta_variable="delta_E2_E2__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="P2">
<role stoichiometry="1" delta_variable="delta_P2_E2__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k11</ci>
<ci>E2_P2</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2__P2_binding">
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="molar" public_interface="in" name="P2"/>
<variable units="molar" public_interface="in" name="E2_P2"/>
<variable units="flux" public_interface="out" name="delta_E2__E2__P2_binding"/>
<variable units="flux" public_interface="out" name="delta_P2_E2__P2_binding"/>
<variable units="flux" public_interface="out" name="delta_E2_P2_E2__P2_binding"/>
<variable units="second_order_rate_constant" name="k12" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k12_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E2_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2__E2__P2_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="P2">
<role stoichiometry="1" direction="forward" delta_variable="delta_P2_E2__P2_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_P2">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2_P2_E2__P2_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k12</ci>
<ci>E2_</ci>
<ci>P2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k12_</ci>
<ci>E2_P2</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2_E4__syn">
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="molar" public_interface="in" name="E2_E4_"/>
<variable units="flux" public_interface="out" name="delta_E2__E2_E4__syn"/>
<variable units="flux" public_interface="out" name="delta_E4__E2_E4__syn"/>
<variable units="flux" public_interface="out" name="delta_E2_E4__E2_E4__syn"/>
<variable units="second_order_rate_constant" name="k13" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k13_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E2_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2__E2_E4__syn" role="reactant"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4__E2_E4__syn" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2_E4__E2_E4__syn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k13</ci>
<ci>E2_</ci>
<ci>E4_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k13_</ci>
<ci>E2_E4_</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2_E4__desyn">
<variable units="molar" public_interface="in" name="E2_E4_"/>
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="flux" public_interface="out" name="delta_E2_E4__E2_E4__desyn"/>
<variable units="flux" public_interface="out" name="delta_E2__E2_E4__desyn"/>
<variable units="flux" public_interface="out" name="delta_E4__E2_E4__desyn"/>
<variable units="first_order_rate_constant" name="k14" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E2_E4_">
<role stoichiometry="1" delta_variable="delta_E2_E4__E2_E4__desyn" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_">
<role stoichiometry="1" delta_variable="delta_E2__E2_E4__desyn" role="product"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" delta_variable="delta_E4__E2_E4__desyn" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k14</ci>
<ci>E2_E4_</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E3__inactivation">
<variable units="molar" public_interface="in" name="E3_P3"/>
<variable units="molar" public_interface="in" name="E3"/>
<variable units="molar" public_interface="in" name="P3"/>
<variable units="flux" public_interface="out" name="delta_E3_P3_E3__inactivation"/>
<variable units="flux" public_interface="out" name="delta_E3_E3__inactivation"/>
<variable units="flux" public_interface="out" name="delta_P3_E3__inactivation"/>
<variable units="first_order_rate_constant" name="k15" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E3_P3">
<role stoichiometry="1" delta_variable="delta_E3_P3_E3__inactivation" role="reactant"/>
</variable_ref>
<variable_ref variable="E3">
<role stoichiometry="1" delta_variable="delta_E3_E3__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="P3">
<role stoichiometry="1" delta_variable="delta_P3_E3__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k15</ci>
<ci>E3_P3</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E3_P3_binding">
<variable units="molar" public_interface="in" name="E3_"/>
<variable units="molar" public_interface="in" name="P3"/>
<variable units="molar" public_interface="in" name="E3_P3"/>
<variable units="flux" public_interface="out" name="delta_E3__E3_P3_binding"/>
<variable units="flux" public_interface="out" name="delta_P3_E3_P3_binding"/>
<variable units="flux" public_interface="out" name="delta_E3_P3_E3_P3_binding"/>
<variable units="second_order_rate_constant" name="k16" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k16_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E3_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E3__E3_P3_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="P3">
<role stoichiometry="1" direction="forward" delta_variable="delta_P3_E3_P3_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E3_P3">
<role stoichiometry="1" direction="forward" delta_variable="delta_E3_P3_E3_P3_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k16</ci>
<ci>E3_</ci>
<ci>P3</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k16_</ci>
<ci>E3_P3</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E4__inactivation">
<variable units="molar" public_interface="in" name="E4_P4"/>
<variable units="molar" public_interface="in" name="P4"/>
<variable units="molar" public_interface="in" name="E4"/>
<variable units="flux" public_interface="out" name="delta_E4_P4_E4__inactivation"/>
<variable units="flux" public_interface="out" name="delta_P4_E4__inactivation"/>
<variable units="flux" public_interface="out" name="delta_E4_E4__inactivation"/>
<variable units="first_order_rate_constant" name="k17" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E4_P4">
<role stoichiometry="1" delta_variable="delta_E4_P4_E4__inactivation" role="reactant"/>
</variable_ref>
<variable_ref variable="P4">
<role stoichiometry="1" delta_variable="delta_P4_E4__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="E4">
<role stoichiometry="1" delta_variable="delta_E4_E4__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k17</ci>
<ci>E4_P4</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E4__P4_binding">
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="molar" public_interface="in" name="P4"/>
<variable units="molar" public_interface="in" name="E4_P4"/>
<variable units="flux" public_interface="out" name="delta_E4__E4__P4_binding"/>
<variable units="flux" public_interface="out" name="delta_P4_E4__P4_binding"/>
<variable units="flux" public_interface="out" name="delta_E4_P4_E4__P4_binding"/>
<variable units="second_order_rate_constant" name="k18" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k18_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4__E4__P4_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="P4">
<role stoichiometry="1" direction="forward" delta_variable="delta_P4_E4__P4_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E4_P4">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4_P4_E4__P4_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k18</ci>
<ci>E4_</ci>
<ci>P4</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k18_</ci>
<ci>E4_P4</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E5__inactivation">
<variable units="molar" public_interface="in" name="E5_P5"/>
<variable units="molar" public_interface="in" name="E5"/>
<variable units="molar" public_interface="in" name="P5"/>
<variable units="flux" public_interface="out" name="delta_E5_P5_E5__inactivation"/>
<variable units="flux" public_interface="out" name="delta_E5_E5__inactivation"/>
<variable units="flux" public_interface="out" name="delta_P5_E5__inactivation"/>
<variable units="first_order_rate_constant" name="k19" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E5_P5">
<role stoichiometry="1" delta_variable="delta_E5_P5_E5__inactivation" role="reactant"/>
</variable_ref>
<variable_ref variable="E5">
<role stoichiometry="1" delta_variable="delta_E5_E5__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="P5">
<role stoichiometry="1" delta_variable="delta_P5_E5__inactivation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k19</ci>
<ci>E5_P5</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E5__P5_binding">
<variable units="molar" public_interface="in" name="E5_"/>
<variable units="molar" public_interface="in" name="P5"/>
<variable units="molar" public_interface="in" name="E5_P5"/>
<variable units="flux" public_interface="out" name="delta_E5__E5__P5_binding"/>
<variable units="flux" public_interface="out" name="delta_P5_E5__P5_binding"/>
<variable units="flux" public_interface="out" name="delta_E5_P5_E5__P5_binding"/>
<variable units="second_order_rate_constant" name="k20" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k20_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E5_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E5__E5__P5_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="P5">
<role stoichiometry="1" direction="forward" delta_variable="delta_P5_E5__P5_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E5_P5">
<role stoichiometry="1" direction="forward" delta_variable="delta_E5_P5_E5__P5_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k20</ci>
<ci>E5_</ci>
<ci>P5</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k20_</ci>
<ci>E5_P5</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E0__E1_binding">
<variable units="molar" public_interface="in" name="E1"/>
<variable units="molar" public_interface="in" name="E0_"/>
<variable units="molar" public_interface="in" name="E0_E1"/>
<variable units="flux" public_interface="out" name="delta_E1_E0__E1_binding"/>
<variable units="flux" public_interface="out" name="delta_E0__E0__E1_binding"/>
<variable units="flux" public_interface="out" name="delta_E0_E1_E0__E1_binding"/>
<variable units="second_order_rate_constant" name="k21" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k21_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E1">
<role stoichiometry="1" direction="forward" delta_variable="delta_E1_E0__E1_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0__E0__E1_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_E1">
<role stoichiometry="1" direction="forward" delta_variable="delta_E0_E1_E0__E1_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k21</ci>
<ci>E1</ci>
<ci>E0_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k21_</ci>
<ci>E0_E1</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E1_activation">
<variable units="molar" public_interface="in" name="E0_E1"/>
<variable units="molar" public_interface="in" name="E0_"/>
<variable units="molar" public_interface="in" name="E1_"/>
<variable units="flux" public_interface="out" name="delta_E0_E1_E1_activation"/>
<variable units="flux" public_interface="out" name="delta_E0__E1_activation"/>
<variable units="flux" public_interface="out" name="delta_E1__E1_activation"/>
<variable units="first_order_rate_constant" name="k22" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E0_E1">
<role stoichiometry="1" delta_variable="delta_E0_E1_E1_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="E0_">
<role stoichiometry="1" delta_variable="delta_E0__E1_activation" role="product"/>
</variable_ref>
<variable_ref variable="E1_">
<role stoichiometry="1" delta_variable="delta_E1__E1_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k22</ci>
<ci>E0_E1</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2_activation">
<variable units="molar" public_interface="in" name="E1_E2"/>
<variable units="molar" public_interface="in" name="E1_"/>
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="flux" public_interface="out" name="delta_E1_E2_E2_activation"/>
<variable units="flux" public_interface="out" name="delta_E1__E2_activation"/>
<variable units="flux" public_interface="out" name="delta_E2__E2_activation"/>
<variable units="first_order_rate_constant" name="k23" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E1_E2">
<role stoichiometry="1" delta_variable="delta_E1_E2_E2_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="E1_">
<role stoichiometry="1" delta_variable="delta_E1__E2_activation" role="product"/>
</variable_ref>
<variable_ref variable="E2_">
<role stoichiometry="1" delta_variable="delta_E2__E2_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k23</ci>
<ci>E1_E2</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E2__E3_binding">
<variable units="molar" public_interface="in" name="E3"/>
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="molar" public_interface="in" name="E2_E3"/>
<variable units="flux" public_interface="out" name="delta_E3_E2__E3_binding"/>
<variable units="flux" public_interface="out" name="delta_E2__E2__E3_binding"/>
<variable units="flux" public_interface="out" name="delta_E2_E3_E2__E3_binding"/>
<variable units="second_order_rate_constant" name="k24" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k24_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E3">
<role stoichiometry="1" direction="forward" delta_variable="delta_E3_E2__E3_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2__E2__E3_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_E3">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2_E3_E2__E3_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k24</ci>
<ci>E3</ci>
<ci>E2_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k24_</ci>
<ci>E2_E3</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E3_activation">
<variable units="molar" public_interface="in" name="E2_E3"/>
<variable units="molar" public_interface="in" name="E2_"/>
<variable units="molar" public_interface="in" name="E3_"/>
<variable units="flux" public_interface="out" name="delta_E2_E3_E3_activation"/>
<variable units="flux" public_interface="out" name="delta_E2__E3_activation"/>
<variable units="flux" public_interface="out" name="delta_E3__E3_activation"/>
<variable units="first_order_rate_constant" name="k25" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E2_E3">
<role stoichiometry="1" delta_variable="delta_E2_E3_E3_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="E2_">
<role stoichiometry="1" delta_variable="delta_E2__E3_activation" role="product"/>
</variable_ref>
<variable_ref variable="E3_">
<role stoichiometry="1" delta_variable="delta_E3__E3_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k25</ci>
<ci>E2_E3</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E3__E4_binding">
<variable units="molar" public_interface="in" name="E4"/>
<variable units="molar" public_interface="in" name="E3_"/>
<variable units="molar" public_interface="in" name="E3_E4"/>
<variable units="flux" public_interface="out" name="delta_E4_E3__E4_binding"/>
<variable units="flux" public_interface="out" name="delta_E3__E3__E4_binding"/>
<variable units="flux" public_interface="out" name="delta_E3_E4_E3__E4_binding"/>
<variable units="second_order_rate_constant" name="k26" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k26_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E4">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4_E3__E4_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E3_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E3__E3__E4_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E3_E4">
<role stoichiometry="1" direction="forward" delta_variable="delta_E3_E4_E3__E4_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k26</ci>
<ci>E4</ci>
<ci>E3_</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k26_</ci>
<ci>E3_E4</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E4_activation">
<variable units="molar" public_interface="in" name="E3_E4"/>
<variable units="molar" public_interface="in" name="E3_"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="flux" public_interface="out" name="delta_E3_E4_E4_activation"/>
<variable units="flux" public_interface="out" name="delta_E3__E4_activation"/>
<variable units="flux" public_interface="out" name="delta_E4__E4_activation"/>
<variable units="first_order_rate_constant" name="k27" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E3_E4">
<role stoichiometry="1" delta_variable="delta_E3_E4_E4_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="E3_">
<role stoichiometry="1" delta_variable="delta_E3__E4_activation" role="product"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" delta_variable="delta_E4__E4_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k27</ci>
<ci>E3_E4</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E4__E5_binding">
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="molar" public_interface="in" name="E5"/>
<variable units="molar" public_interface="in" name="E4_E5"/>
<variable units="flux" public_interface="out" name="delta_E4__E4__E5_binding"/>
<variable units="flux" public_interface="out" name="delta_E5_E4__E5_binding"/>
<variable units="flux" public_interface="out" name="delta_E4_E5_E4__E5_binding"/>
<variable units="second_order_rate_constant" name="k28" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k28_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E4_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4__E4__E5_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E5">
<role stoichiometry="1" direction="forward" delta_variable="delta_E5_E4__E5_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E4_E5">
<role stoichiometry="1" direction="forward" delta_variable="delta_E4_E5_E4__E5_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k28</ci>
<ci>E4_</ci>
<ci>E5</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k28_</ci>
<ci>E4_E5</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E5_activation">
<variable units="molar" public_interface="in" name="E4_E5"/>
<variable units="molar" public_interface="in" name="E4_"/>
<variable units="molar" public_interface="in" name="E5_"/>
<variable units="flux" public_interface="out" name="delta_E4_E5_E5_activation"/>
<variable units="flux" public_interface="out" name="delta_E4__E5_activation"/>
<variable units="flux" public_interface="out" name="delta_E5__E5_activation"/>
<variable units="first_order_rate_constant" name="k29" initial_value="6.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="no">
<variable_ref variable="E4_E5">
<role stoichiometry="1" delta_variable="delta_E4_E5_E5_activation" role="reactant"/>
</variable_ref>
<variable_ref variable="E4_">
<role stoichiometry="1" delta_variable="delta_E4__E5_activation" role="product"/>
</variable_ref>
<variable_ref variable="E5_">
<role stoichiometry="1" delta_variable="delta_E5__E5_activation" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<times/>
<ci>k29</ci>
<ci>E4_E5</ci>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="E1__E2_binding">
<variable units="molar" public_interface="in" name="E1_"/>
<variable units="molar" public_interface="in" name="E2"/>
<variable units="molar" public_interface="in" name="E1_E2"/>
<variable units="flux" public_interface="out" name="delta_E1__E1__E2_binding"/>
<variable units="flux" public_interface="out" name="delta_E2_E1__E2_binding"/>
<variable units="flux" public_interface="out" name="delta_E1_E2_E1__E2_binding"/>
<variable units="second_order_rate_constant" name="k30" initial_value="600000000.0"/>
<variable units="first_order_rate_constant" name="k30_" initial_value="30.0"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E1_">
<role stoichiometry="1" direction="forward" delta_variable="delta_E1__E1__E2_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E2">
<role stoichiometry="1" direction="forward" delta_variable="delta_E2_E1__E2_binding" role="reactant"/>
</variable_ref>
<variable_ref variable="E1_E2">
<role stoichiometry="1" direction="forward" delta_variable="delta_E1_E2_E1__E2_binding" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k30</ci>
<ci>E1_</ci>
<ci>E2</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k30_</ci>
<ci>E1_E2</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="ligand_receptor_binding" component_1="R"/>
<map_variables variable_2="R" variable_1="R"/>
<map_variables variable_2="delta_R_ligand_receptor_binding" variable_1="delta_R_ligand_receptor_binding"/>
</connection>
<connection>
<map_components component_2="ligand_receptor_binding" component_1="C"/>
<map_variables variable_2="C" variable_1="C"/>
<map_variables variable_2="delta_C_ligand_receptor_binding" variable_1="delta_C_ligand_receptor_binding"/>
</connection>
<connection>
<map_components component_2="receptor_dimerisation" component_1="C"/>
<map_variables variable_2="C" variable_1="C"/>
<map_variables variable_2="delta_C_receptor_dimerisation" variable_1="delta_C_receptor_dimerisation"/>
</connection>
<connection>
<map_components component_2="receptor_dimerisation" component_1="C2"/>
<map_variables variable_2="C2" variable_1="C2"/>
<map_variables variable_2="delta_C2_receptor_dimerisation" variable_1="delta_C2_receptor_dimerisation"/>
</connection>
<connection>
<map_components component_2="dimerised_receptor_activation" component_1="C2"/>
<map_variables variable_2="C2" variable_1="C2"/>
<map_variables variable_2="delta_C2_dimerised_receptor_activation" variable_1="delta_C2_dimerised_receptor_activation"/>
</connection>
<connection>
<map_components component_2="dimerised_receptor_activation" component_1="C_"/>
<map_variables variable_2="C_" variable_1="C_"/>
<map_variables variable_2="delta_C__dimerised_receptor_activation" variable_1="delta_C__dimerised_receptor_activation"/>
</connection>
<connection>
<map_components component_2="receptor_adaptor_complex_syn" component_1="C_"/>
<map_variables variable_2="C_" variable_1="C_"/>
<map_variables variable_2="delta_C__receptor_adaptor_complex_syn" variable_1="delta_C__receptor_adaptor_complex_syn"/>
</connection>
<connection>
<map_components component_2="receptor_adaptors_complex_syn2" component_1="C_"/>
<map_variables variable_2="C_" variable_1="C_"/>
<map_variables variable_2="delta_C__receptor_adaptors_complex_syn2" variable_1="delta_C__receptor_adaptors_complex_syn2"/>
</connection>
<connection>
<map_components component_2="ligand_receptor_binding" component_1="L"/>
<map_variables variable_2="L" variable_1="L"/>
<map_variables variable_2="delta_L_ligand_receptor_binding" variable_1="delta_L_ligand_receptor_binding"/>
</connection>
<connection>
<map_components component_2="E0_E4__desyn" component_1="A2_"/>
<map_variables variable_2="A2_" variable_1="A2_"/>
<map_variables variable_2="delta_A2__E0_E4__desyn" variable_1="delta_A2__E0_E4__desyn"/>
</connection>
<connection>
<map_components component_2="E0_E4__desyn" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E0_E4__desyn" variable_1="delta_E4__E0_E4__desyn"/>
</connection>
<connection>
<map_components component_2="E2_E4__desyn" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E2_E4__desyn" variable_1="delta_E4__E2_E4__desyn"/>
</connection>
<connection>
<map_components component_2="E5_activation" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E5_activation" variable_1="delta_E4__E5_activation"/>
</connection>
<connection>
<map_components component_2="E0_E4__syn" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E0_E4__syn" variable_1="delta_E4__E0_E4__syn"/>
</connection>
<connection>
<map_components component_2="E2_E4__syn" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E2_E4__syn" variable_1="delta_E4__E2_E4__syn"/>
</connection>
<connection>
<map_components component_2="E4__P4_binding" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E4__P4_binding" variable_1="delta_E4__E4__P4_binding"/>
</connection>
<connection>
<map_components component_2="E4__E5_binding" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E4__E5_binding" variable_1="delta_E4__E4__E5_binding"/>
</connection>
<connection>
<map_components component_2="E4_activation" component_1="E4_"/>
<map_variables variable_2="E4_" variable_1="E4_"/>
<map_variables variable_2="delta_E4__E4_activation" variable_1="delta_E4__E4_activation"/>
</connection>
<connection>
<map_components component_2="E0_E4__syn" component_1="E0_E4_"/>
<map_variables variable_2="E0_E4_" variable_1="E0_E4_"/>
<map_variables variable_2="delta_E0_E4__E0_E4__syn" variable_1="delta_E0_E4__E0_E4__syn"/>
</connection>
<connection>
<map_components component_2="E0_E4__desyn" component_1="E0_E4_"/>
<map_variables variable_2="E0_E4_" variable_1="E0_E4_"/>
<map_variables variable_2="delta_E0_E4__E0_E4__desyn" variable_1="delta_E0_E4__E0_E4__desyn"/>
</connection>
<connection>
<map_components component_2="E1_activation" component_1="E1_"/>
<map_variables variable_2="E1_" variable_1="E1_"/>
<map_variables variable_2="delta_E1__E1_activation" variable_1="delta_E1__E1_activation"/>
</connection>
<connection>
<map_components component_2="E2_activation" component_1="E1_"/>
<map_variables variable_2="E1_" variable_1="E1_"/>
<map_variables variable_2="delta_E1__E2_activation" variable_1="delta_E1__E2_activation"/>
</connection>
<connection>
<map_components component_2="E1__P1_binding" component_1="E1_"/>
<map_variables variable_2="E1_" variable_1="E1_"/>
<map_variables variable_2="delta_E1__E1__P1_binding" variable_1="delta_E1__E1__P1_binding"/>
</connection>
<connection>
<map_components component_2="E1__E2_binding" component_1="E1_"/>
<map_variables variable_2="E1_" variable_1="E1_"/>
<map_variables variable_2="delta_E1__E1__E2_binding" variable_1="delta_E1__E1__E2_binding"/>
</connection>
<connection>
<map_components component_2="E1__inactivation" component_1="E1"/>
<map_variables variable_2="E1" variable_1="E1"/>
<map_variables variable_2="delta_E1_E1__inactivation" variable_1="delta_E1_E1__inactivation"/>
</connection>
<connection>
<map_components component_2="E0__E1_binding" component_1="E1"/>
<map_variables variable_2="E1" variable_1="E1"/>
<map_variables variable_2="delta_E1_E0__E1_binding" variable_1="delta_E1_E0__E1_binding"/>
</connection>
<connection>
<map_components component_2="adaptor_heterodimer_syn" component_1="A1"/>
<map_variables variable_2="A1" variable_1="A1"/>
<map_variables variable_2="delta_A1_adaptor_heterodimer_syn" variable_1="delta_A1_adaptor_heterodimer_syn"/>
</connection>
<connection>
<map_components component_2="receptor_adaptor_complex_syn" component_1="A1"/>
<map_variables variable_2="A1" variable_1="A1"/>
<map_variables variable_2="delta_A1_receptor_adaptor_complex_syn" variable_1="delta_A1_receptor_adaptor_complex_syn"/>
</connection>
<connection>
<map_components component_2="adaptor_heterodimer_syn" component_1="A2"/>
<map_variables variable_2="A2" variable_1="A2"/>
<map_variables variable_2="delta_A2_adaptor_heterodimer_syn" variable_1="delta_A2_adaptor_heterodimer_syn"/>
</connection>
<connection>
<map_components component_2="receptor_adaptors_complex_syn1" component_1="A2"/>
<map_variables variable_2="A2" variable_1="A2"/>
<map_variables variable_2="delta_A2_receptor_adaptors_complex_syn1" variable_1="delta_A2_receptor_adaptors_complex_syn1"/>
</connection>
<connection>
<map_components component_2="receptor_adaptors_complex_syn1" component_1="E0_"/>
<map_variables variable_2="E0_" variable_1="E0_"/>
<map_variables variable_2="delta_E0__receptor_adaptors_complex_syn1" variable_1="delta_E0__receptor_adaptors_complex_syn1"/>
</connection>
<connection>
<map_components component_2="receptor_adaptors_complex_syn2" component_1="E0_"/>
<map_variables variable_2="E0_" variable_1="E0_"/>
<map_variables variable_2="delta_E0__receptor_adaptors_complex_syn2" variable_1="delta_E0__receptor_adaptors_complex_syn2"/>
</connection>
<connection>
<map_components component_2="E1_activation" component_1="E0_"/>
<map_variables variable_2="E0_" variable_1="E0_"/>
<map_variables variable_2="delta_E0__E1_activation" variable_1="delta_E0__E1_activation"/>
</connection>
<connection>
<map_components component_2="E0_E4__syn" component_1="E0_"/>
<map_variables variable_2="E0_" variable_1="E0_"/>
<map_variables variable_2="delta_E0__E0_E4__syn" variable_1="delta_E0__E0_E4__syn"/>
</connection>
<connection>
<map_components component_2="E0__E1_binding" component_1="E0_"/>
<map_variables variable_2="E0_" variable_1="E0_"/>
<map_variables variable_2="delta_E0__E0__E1_binding" variable_1="delta_E0__E0__E1_binding"/>
</connection>
<connection>
<map_components component_2="receptor_adaptor_complex_syn" component_1="C_A1"/>
<map_variables variable_2="C_A1" variable_1="C_A1"/>
<map_variables variable_2="delta_C_A1_receptor_adaptor_complex_syn" variable_1="delta_C_A1_receptor_adaptor_complex_syn"/>
</connection>
<connection>
<map_components component_2="E0_E4__desyn" component_1="C_A1"/>
<map_variables variable_2="C_A1" variable_1="C_A1"/>
<map_variables variable_2="delta_C_A1_E0_E4__desyn" variable_1="delta_C_A1_E0_E4__desyn"/>
</connection>
<connection>
<map_components component_2="receptor_adaptors_complex_syn1" component_1="C_A1"/>
<map_variables variable_2="C_A1" variable_1="C_A1"/>
<map_variables variable_2="delta_C_A1_receptor_adaptors_complex_syn1" variable_1="delta_C_A1_receptor_adaptors_complex_syn1"/>
</connection>
<connection>
<map_components component_2="E1__inactivation" component_1="P1"/>
<map_variables variable_2="P1" variable_1="P1"/>
<map_variables variable_2="delta_P1_E1__inactivation" variable_1="delta_P1_E1__inactivation"/>
</connection>
<connection>
<map_components component_2="E1__P1_binding" component_1="P1"/>
<map_variables variable_2="P1" variable_1="P1"/>
<map_variables variable_2="delta_P1_E1__P1_binding" variable_1="delta_P1_E1__P1_binding"/>
</connection>
<connection>
<map_components component_2="E2_activation" component_1="E2_"/>
<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E2_activation" variable_1="delta_E2__E2_activation"/>
</connection>
<connection>
<map_components component_2="E3_activation" component_1="E2_"/>
<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E3_activation" variable_1="delta_E2__E3_activation"/>
</connection>
<connection>
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<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E2__P2_binding" variable_1="delta_E2__E2__P2_binding"/>
</connection>
<connection>
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<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E2_E4__syn" variable_1="delta_E2__E2_E4__syn"/>
</connection>
<connection>
<map_components component_2="E2__E3_binding" component_1="E2_"/>
<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E2__E3_binding" variable_1="delta_E2__E2__E3_binding"/>
</connection>
<connection>
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<map_variables variable_2="E2" variable_1="E2"/>
<map_variables variable_2="delta_E2_E2__inactivation" variable_1="delta_E2_E2__inactivation"/>
</connection>
<connection>
<map_components component_2="E1__E2_binding" component_1="E2"/>
<map_variables variable_2="E2" variable_1="E2"/>
<map_variables variable_2="delta_E2_E1__E2_binding" variable_1="delta_E2_E1__E2_binding"/>
</connection>
<connection>
<map_components component_2="E2__inactivation" component_1="P2"/>
<map_variables variable_2="P2" variable_1="P2"/>
<map_variables variable_2="delta_P2_E2__inactivation" variable_1="delta_P2_E2__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="P2" variable_1="P2"/>
<map_variables variable_2="delta_P2_E2__P2_binding" variable_1="delta_P2_E2__P2_binding"/>
</connection>
<connection>
<map_components component_2="E1__P1_binding" component_1="E1_P1"/>
<map_variables variable_2="E1_P1" variable_1="E1_P1"/>
<map_variables variable_2="delta_E1_P1_E1__P1_binding" variable_1="delta_E1_P1_E1__P1_binding"/>
</connection>
<connection>
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<map_variables variable_2="E1_P1" variable_1="E1_P1"/>
<map_variables variable_2="delta_E1_P1_E1__inactivation" variable_1="delta_E1_P1_E1__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="E2_P2" variable_1="E2_P2"/>
<map_variables variable_2="delta_E2_P2_E2__P2_binding" variable_1="delta_E2_P2_E2__P2_binding"/>
</connection>
<connection>
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<map_variables variable_2="E2_P2" variable_1="E2_P2"/>
<map_variables variable_2="delta_E2_P2_E2__inactivation" variable_1="delta_E2_P2_E2__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="E2_" variable_1="E2_"/>
<map_variables variable_2="delta_E2__E2_E4__desyn" variable_1="delta_E2__E2_E4__desyn"/>
</connection>
<connection>
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<map_variables variable_2="E3_" variable_1="E3_"/>
<map_variables variable_2="delta_E3__E3_activation" variable_1="delta_E3__E3_activation"/>
</connection>
<connection>
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<map_variables variable_2="delta_E3__E4_activation" variable_1="delta_E3__E4_activation"/>
</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="delta_E3__E3__E4_binding" variable_1="delta_E3__E3__E4_binding"/>
</connection>
<connection>
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<map_variables variable_2="delta_E3_E3__inactivation" variable_1="delta_E3_E3__inactivation"/>
</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="delta_E3_P3_E3__inactivation" variable_1="delta_E3_P3_E3__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="P3" variable_1="P3"/>
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</connection>
<connection>
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<map_variables variable_2="delta_P3_E3_P3_binding" variable_1="delta_P3_E3_P3_binding"/>
</connection>
<connection>
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<map_variables variable_2="E4" variable_1="E4"/>
<map_variables variable_2="delta_E4_E4__inactivation" variable_1="delta_E4_E4__inactivation"/>
</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="delta_E4_P4_E4__inactivation" variable_1="delta_E4_P4_E4__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="delta_P4_E4__inactivation" variable_1="delta_P4_E4__inactivation"/>
</connection>
<connection>
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<map_variables variable_2="delta_P4_E4__P4_binding" variable_1="delta_P4_E4__P4_binding"/>
</connection>
<connection>
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<map_variables variable_2="E5_" variable_1="E5_"/>
<map_variables variable_2="delta_E5__E5_activation" variable_1="delta_E5__E5_activation"/>
</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="A1A2" variable_1="A1A2"/>
<map_variables variable_2="delta_A1A2_receptor_adaptors_complex_syn2" variable_1="delta_A1A2_receptor_adaptors_complex_syn2"/>
</connection>
<connection>
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<map_variables variable_2="delta_A1A2_adaptor_heterodimer_syn" variable_1="delta_A1A2_adaptor_heterodimer_syn"/>
</connection>
<connection>
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<map_variables variable_2="delta_E2_E4__E2_E4__syn" variable_1="delta_E2_E4__E2_E4__syn"/>
</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="E0_E1" variable_1="E0_E1"/>
<map_variables variable_2="delta_E0_E1_E0__E1_binding" variable_1="delta_E0_E1_E0__E1_binding"/>
</connection>
<connection>
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<map_variables variable_2="delta_E0_E1_E1_activation" variable_1="delta_E0_E1_E1_activation"/>
</connection>
<connection>
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<map_variables variable_2="delta_E1_E2_E1__E2_binding" variable_1="delta_E1_E2_E1__E2_binding"/>
</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="E2_E3" variable_1="E2_E3"/>
<map_variables variable_2="delta_E2_E3_E2__E3_binding" variable_1="delta_E2_E3_E2__E3_binding"/>
</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="delta_E3_E4_E4_activation" variable_1="delta_E3_E4_E4_activation"/>
</connection>
<connection>
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<map_variables variable_2="E4_E5" variable_1="E4_E5"/>
<map_variables variable_2="delta_E4_E5_E4__E5_binding" variable_1="delta_E4_E5_E4__E5_binding"/>
</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="C"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
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<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
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<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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<map_variables variable_2="time" variable_1="time"/>
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<connection>
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</connection>
<connection>
<map_components component_2="global_variables" component_1="E4_P4"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="P4"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E5_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E5"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="P5"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E5_P5"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="A1A2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E2_E4_"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E0_E1"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E1_E2"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E2_E3"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E3_E4"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="global_variables" component_1="E4_E5"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<rdf:RDF>
<rdf:Seq rdf:about="rdf:#90719662-6c1b-4873-b40f-59207b17c952">
<rdf:li rdf:resource="rdf:#d093c98d-fa49-4571-ae46-552982922e20"/>
<rdf:li rdf:resource="rdf:#1e0103cd-e8ee-4c17-bf4f-afaa296ed414"/>
</rdf:Seq>
<rdf:Description rdf:about="#E1_P1">
<dcterms:alternative>
transition complex between an active substrate and its deactivating
enzyme
</dcterms:alternative>
<dc:title>E1_P1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E2">
<dcterms:alternative>2nd inactive signaling enzyme</dcterms:alternative>
<dc:title>E2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#99bedfc6-076b-4961-baa6-2ed50f0bbd98">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A.</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#fb083531-6097-4f33-9bc0-5e3ea956afd3">
<dcterms:W3CDTF>2002-07-18</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#R">
<dcterms:alternative>free receptor</dcterms:alternative>
<dc:title>R</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a3044bcb-0f43-4c75-95a5-c1d4314437f2">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1d5a4f33-f2ad-40df-b170-a974a8596632">
<vCard:N rdf:resource="rdf:#6f0817d5-62a4-46b3-a092-845c7970ea7d"/>
</rdf:Description>
<rdf:Description rdf:about="#E2_E4_">
<dcterms:alternative>
transition complex in feedback mediated by enzyme E4_
</dcterms:alternative>
<dc:title>E2_E4_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#85047f45-03e5-4a17-b05d-4adc4884ad15">
<vCard:ORG rdf:resource="rdf:#b768fa0c-50bb-4d92-b090-9fdf99a6e97b"/>
<vCard:EMAIL rdf:resource="rdf:#b5c4a50d-e180-42e3-a9dc-cb7f6a06587d"/>
<vCard:N rdf:resource="rdf:#056385f8-2499-4d0a-92cc-348e4e4367d2"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b7a83da7-b3a2-441f-8dce-98f8d9c5eaf5">
<vCard:Given>Douglas</vCard:Given>
<vCard:Family>Lauffenburger</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="#L">
<dcterms:alternative>free ligand</dcterms:alternative>
<dc:title>L</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E2_P2">
<dcterms:alternative>
transition complex between an active substrate and its deactivating
enzyme
</dcterms:alternative>
<dc:title>E2_P2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4a9e6b79-98bb-403d-b33f-5d51e2273505">
<dcterms:modified rdf:resource="rdf:#1aaf4086-910e-475b-97f8-cac209f4d259"/>
<rdf:value>
Changed unit dimensions E1_ to make them consistent.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#60e428cb-6942-488b-924b-8bab9112ca4a"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e728fc7e-d883-4e6f-b6e5-d482cebddab6">
<vCard:N rdf:resource="rdf:#c9eef482-cd2e-431a-8f0b-76cc7e235253"/>
</rdf:Description>
<rdf:Description rdf:about="#E0_E4_">
<dcterms:alternative>
transition complex in feedback, mediated by E4_
</dcterms:alternative>
<dc:title>E0_E4_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#C">
<dcterms:alternative>ligand-bound receptor</dcterms:alternative>
<dc:title>C</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E2_E3">
<dcterms:alternative>
transition complex between an inactive substrate and its activator
</dcterms:alternative>
<dc:title>E2_E3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#60e428cb-6942-488b-924b-8bab9112ca4a">
<vCard:N rdf:resource="rdf:#51e8329d-9129-45e0-8f89-7fea198df138"/>
</rdf:Description>
<rdf:Description rdf:about="#C_">
<dcterms:alternative>
dimerised and activated receptor
</dcterms:alternative>
<dc:title>C_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6f0817d5-62a4-46b3-a092-845c7970ea7d">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A.</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6ce1bf38-8f04-4d32-825d-72cbf1a0b871">
<dcterms:modified rdf:resource="rdf:#fb083531-6097-4f33-9bc0-5e3ea956afd3"/>
<rdf:value>
Added more metadata.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#e5f58c72-8e63-4daf-9255-9863b4b29308"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c25a35c1-a3a8-4511-a175-b3d4f37aa953">
<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="rdf:#51e8329d-9129-45e0-8f89-7fea198df138">
<vCard:Given>Peter</vCard:Given>
<vCard:Family>Villiger</vCard:Family>
<vCard:Other>J</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="#E2_">
<dcterms:alternative>
2nd activated signaling enzyme
</dcterms:alternative>
<dc:title>E2_act</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#645a373a-9e73-4314-adb1-35d08a43ec61">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1aaf4086-910e-475b-97f8-cac209f4d259">
<dcterms:W3CDTF>2005-04-26</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#E4">
<dcterms:alternative>4th inactive signaling enzyme</dcterms:alternative>
<dc:title>E4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E0_">
<dcterms:alternative>adaptors 1 + 2 complex</dcterms:alternative>
<dcterms:alternative>receptor-ligand dimer</dcterms:alternative>
<dc:title>E0_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#afe21825-2db5-4b29-afc4-0b2304659eeb">
<bqs:subject_type>keyword</bqs:subject_type>
<rdf:value>signal transduction</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#056385f8-2499-4d0a-92cc-348e4e4367d2">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#4226e025-1806-4bd9-9fa6-c484a1fed202">
<dcterms:W3CDTF>2002-01-22</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#740b9b4b-3cf8-419a-91ee-d3c397c28727">
<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#8b6d60ad-82fd-4172-bfb8-4ec0a525315f">
<dc:creator rdf:resource="rdf:#c25a35c1-a3a8-4511-a175-b3d4f37aa953"/>
<rdf:value>This is the CellML description of Asthagiri and Lauffenburger's
mathematical model of the mitogen-activated protein kinase (MAPK)
cascade (2001). They examine MAPK pathway dynamics, especially the
role of negative feedback mechanisms in generating signal adaptation.</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#E4_">
<dcterms:alternative>
4th activated signaling enzyme
</dcterms:alternative>
<dc:title>E4_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#C_A1">
<dcterms:alternative>active receptor-ligand dimer</dcterms:alternative>
<dcterms:alternative>adaptor 1 complex</dcterms:alternative>
<dc:title>C_A1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b1e1950c-c0b3-49c0-ac64-65113cb80376">
<vCard:N rdf:resource="rdf:#a3044bcb-0f43-4c75-95a5-c1d4314437f2"/>
</rdf:Description>
<rdf:Description rdf:about="#E1_E2">
<dcterms:alternative>
transition complex between an inactive substrate and its activator
</dcterms:alternative>
<dc:title>E1_E2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3a23251d-f198-4f35-bcb6-e841ec25b2b6">
<vCard:Given>Anand</vCard:Given>
<vCard:Family>Asthagiri</vCard:Family>
<vCard:Other>R</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="#A1A2">
<dcterms:alternative>adaptor heterodimer</dcterms:alternative>
<dc:title>A1A2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E3">
<dcterms:alternative>3rd inactive signaling enzyme</dcterms:alternative>
<dc:title>E3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E1">
<dcterms:alternative>1st inactive signaling enzyme</dcterms:alternative>
<dc:title>E1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E0_E1">
<dcterms:alternative>
transition complex between an inactive substrate and its activator
</dcterms:alternative>
<dc:title>E0_E1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#A2_">
<dcterms:alternative>non-functional second adaptor</dcterms:alternative>
<dc:title>A2_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E5">
<dcterms:alternative>5th inactive signaling enzyme</dcterms:alternative>
<dc:title>E5</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E3_E4">
<dcterms:alternative>
transition complex between an inactive substrate and its activator
</dcterms:alternative>
<dc:title>E3_E4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E3_P3">
<dcterms:alternative>
transition complex between an active substrate and its deactivating
enzyme
</dcterms:alternative>
<dc:title>E3_P3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6a71ea93-d400-4d9e-95b8-2d56180e94d2">
<dcterms:modified rdf:resource="rdf:#740b9b4b-3cf8-419a-91ee-d3c397c28727"/>
<rdf:value>
Added publication date information.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#b1e1950c-c0b3-49c0-ac64-65113cb80376"/>
</rdf:Description>
<rdf:Description rdf:about="#A2">
<dcterms:alternative>free second adaptor</dcterms:alternative>
<dc:title>A2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#A1">
<dcterms:alternative>free first adaptor</dcterms:alternative>
<dc:title>A1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b5c4a50d-e180-42e3-a9dc-cb7f6a06587d">
<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="#E4_P4">
<dcterms:alternative>
transition complex between an active substrate and its deactivating
enzyme
</dcterms:alternative>
<dc:title>E4_P4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#52c8f220-a850-4ccf-8e0d-fe72ce345141">
<dc:subject rdf:resource="rdf:#afe21825-2db5-4b29-afc4-0b2304659eeb"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f07116b6-f284-48b1-b2f0-9fd1ab326ede">
<dcterms:W3CDTF>2001-10-25</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1e0103cd-e8ee-4c17-bf4f-afaa296ed414">
<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
<vCard:N rdf:resource="rdf:#b7a83da7-b3a2-441f-8dce-98f8d9c5eaf5"/>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>The University of Auckland, Bioengineering Research Group</dc:publisher>
<cmeta:modification rdf:resource="rdf:#1bb8f027-aa59-4607-b889-af48b3bfa514"/>
<cmeta:modification rdf:resource="rdf:#4a9e6b79-98bb-403d-b33f-5d51e2273505"/>
<cmeta:modification rdf:resource="rdf:#6a71ea93-d400-4d9e-95b8-2d56180e94d2"/>
<cmeta:modification rdf:resource="rdf:#6ce1bf38-8f04-4d32-825d-72cbf1a0b871"/>
<cmeta:modification rdf:resource="rdf:#d427da76-3e05-4e47-83a7-2fbc8e8a0d8f"/>
<cmeta:modification rdf:resource="rdf:#f102446e-96fa-499c-a9d3-9f695218f750"/>
<dcterms:created rdf:resource="rdf:#f07116b6-f284-48b1-b2f0-9fd1ab326ede"/>
<dc:creator rdf:resource="rdf:#85047f45-03e5-4a17-b05d-4adc4884ad15"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#05ed1bc3-35b1-451c-b786-b739b0bedf3a">
<dcterms:W3CDTF>2002-08-27</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#204e262c-4fe0-4863-b80c-3a19ce608daa">
<dc:title>Biotechnology Progress</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d427da76-3e05-4e47-83a7-2fbc8e8a0d8f">
<dcterms:modified rdf:resource="rdf:#4226e025-1806-4bd9-9fa6-c484a1fed202"/>
<rdf:value>
Updated metadata to conform to the 16/1/02 CellML Metadata 1.0
Specification.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#cf0d255d-4b1a-4cf2-8ec4-d7ce04b08226"/>
</rdf:Description>
<rdf:Description rdf:about="#P4">
<dcterms:alternative>4th deactivating enzyme</dcterms:alternative>
<dc:title>P4</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#P1">
<dcterms:alternative>1st deactivating enzyme</dcterms:alternative>
<dc:title>P1</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#1bb8f027-aa59-4607-b889-af48b3bfa514">
<dcterms:modified rdf:resource="rdf:#05ed1bc3-35b1-451c-b786-b739b0bedf3a"/>
<rdf:value>
Corrected the initial value of variable 'k6_' in component
'adaptor_heterodimer_syn'.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#1d5a4f33-f2ad-40df-b170-a974a8596632"/>
</rdf:Description>
<rdf:Description rdf:about="#P3">
<dcterms:alternative>3rd deactivating enzyme</dcterms:alternative>
<dc:title>P3</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#P2">
<dcterms:alternative>2nd deactivating enzyme</dcterms:alternative>
<dc:title>P2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#P5">
<dcterms:alternative>5th deactivating enzyme</dcterms:alternative>
<dc:title>P5</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E3_">
<dcterms:alternative>
3rd activated signaling enzyme
</dcterms:alternative>
<dc:title>E3_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#a5f803a5-0526-46d7-8826-031844bddbd0">
<bqs:Pubmed_id>11312698</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#03f56d60-970b-4271-b83c-1d7a957a5aee"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#cf0d255d-4b1a-4cf2-8ec4-d7ce04b08226">
<vCard:N rdf:resource="rdf:#99bedfc6-076b-4961-baa6-2ed50f0bbd98"/>
</rdf:Description>
<rdf:Description rdf:about="#E5_P5">
<dcterms:alternative>
transition complex between an active substrate and its deactivating
enzyme
</dcterms:alternative>
<dc:title>E5_P5</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E4_E5">
<dcterms:alternative>
transition complex between an inactive substrate and its activator
</dcterms:alternative>
<dc:title>E4_E5</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#6e3c0e1f-a36e-4f42-b194-394d59966238">
<dcterms:W3CDTF>2001-03-01</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#E1_">
<dcterms:alternative>
1st activated signaling enzyme
</dcterms:alternative>
<dc:title>E1_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#f102446e-96fa-499c-a9d3-9f695218f750">
<dcterms:modified rdf:resource="rdf:#6a1d9947-9f67-4de1-a014-110eef786ba9"/>
<rdf:value>
Altered connections after chacking the model with the validator.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#e728fc7e-d883-4e6f-b6e5-d482cebddab6"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#03f56d60-970b-4271-b83c-1d7a957a5aee">
<dc:creator rdf:resource="rdf:#90719662-6c1b-4873-b40f-59207b17c952"/>
<dc:title>A Compuational Study of Feedback Effects on Signal Dynamics in a Mitogen-Activated Protein Kinase (MAPK) Pathway Model</dc:title>
<bqs:volume>17</bqs:volume>
<bqs:first_page>227</bqs:first_page>
<bqs:Journal rdf:resource="rdf:#204e262c-4fe0-4863-b80c-3a19ce608daa"/>
<dcterms:issued rdf:resource="rdf:#6e3c0e1f-a36e-4f42-b194-394d59966238"/>
<bqs:last_page>239</bqs:last_page>
</rdf:Description>
<rdf:Description rdf:about="rdf:#e5f58c72-8e63-4daf-9255-9863b4b29308">
<vCard:N rdf:resource="rdf:#645a373a-9e73-4314-adb1-35d08a43ec61"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#b768fa0c-50bb-4d92-b090-9fdf99a6e97b">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Research Group</vCard:Orgunit>
</rdf:Description>
<rdf:Description rdf:about="#C2">
<dcterms:alternative>
ligand-bound and dimerised receptor
</dcterms:alternative>
<dc:title>C2</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#E5_">
<dcterms:alternative>
5th activated signaling enzyme
</dcterms:alternative>
<dc:title>E5_</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#c9eef482-cd2e-431a-8f0b-76cc7e235253">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
</rdf:Description>
<rdf:Description rdf:about="rdf:#d093c98d-fa49-4571-ae46-552982922e20">
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The mitogen-activated protein kinase (MAPK) cascade, 2001
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