Location: Huang, Ferrell, 1996 @ 54cb949ebc5a / huang_ferrell_1996.cellml

Author:
Hanne <Hanne@hanne-nielsens-macbook.local>
Date:
2010-07-27 09:55:18+12:00
Desc:
Added new xu and sessio nfile
Permanent Source URI:
https://models.cellml.org/workspace/huang_ferrell_1996/rawfile/54cb949ebc5a7da5467e973e014f6d8d4c600cbd/huang_ferrell_1996.cellml

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<!--
This CellML file was generated on 10/19/2007 at 1:20:11 at PM using:

COR (0.9.31.769)
Copyright 2002-2007 Dr Alan Garny
http://COR.physiol.ox.ac.uk/ - COR@physiol.ox.ac.uk

CellML 1.0 was used to generate this cellular model
http://www.CellML.org/
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  <documentation xmlns="http://cellml.org/tmp-documentation">
    <article>
      <articleinfo>
        <title>The Mitogen-Activated Protein Kinase (MAPK) Cascade</title>
        <author>
          <firstname>James</firstname>
          <surname>Lawson</surname>
          <affiliation>
            <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
          </affiliation>
        </author>
      </articleinfo>
      <section id="sec_status">
        <title>Model Status</title>
        <para>
            This CellML model runs in both OpenCell and COR to reproduce the results given by running the Mathematica description of the model (provided by the original model author) using the Mathematica NDSolve integration algorithm. The units have been checked and they are consistent.
          </para>
      </section>
      <sect1 id="sec_structure">
        <title>Model Structure</title>
        <para>
ABSTRACT: The mitogen-activated protein kinase (MAPK) cascade is a highly conserved series of three protein kinases implicated in diverse biological processes. Here we demonstrate that the cascade arrangement has unexpected consequences for the dynamics of MAPK signaling. We solved the rate equations for the cascade numerically and found that MAPK is predicted to behave like a highly cooperative enzyme, even though it was not assumed that any of the enzymes in the cascade were regulated cooperatively. Measurements of MAPK activation in Xenopus oocyte extracts confirmed this prediction. The stimulus/response curve of the MAPK was found to be as steep as that of a cooperative enzyme with a Hill coefficient of 4-5, well in excess of that of the classical allosteric protein hemoglobin. The shape of the MAPK stimulus/ response curve may make the cascade particularly appropriate for mediating processes like mitogenesis, cell fate induction, and oocyte maturation, where a cell switches from one discrete state to another.
</para>
       
        <para>
The original paper reference is cited below:
</para>
        <para>
Ultrasensitivity in the mitogen-activated protein cascade, Chi-Ying F. Huang and James E. Ferrell, Jr., 1996, <emphasis>Proc. Natl. Acad. Sci. USA</emphasis>
, 93, 10078-10083. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/8816754">PubMed ID: 8816754</ulink>
        </para>
        
        <informalfigure float="0" id="fig_pathway_diagram">
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              <objectinfo>
                <title>the conventional rendering of the MAPK cascade</title>
              </objectinfo>
              <imagedata fileref="huang_ferrell_1996.png"/>
            </imageobject>
          </mediaobject>
          <caption>Schematic diagram of the MAPK cascade described by the model.</caption>
        </informalfigure>
        
      </sect1>
    </article>
  </documentation>
  
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      <variable name="mekstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="mekstarstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="mekstarmosstar" public_interface="in" units="micromolar"/>
      <variable name="mapkmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mosstar" public_interface="in" units="micromolar"/>
      <variable name="d3" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k3" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekmosstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a3</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <apply>
                           <minus/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <apply>
                                    <minus/>
                                    <apply>
                                       <minus/>
                                       <apply>
                                          <minus/>
                                          <ci>mektot</ci>
                                          <ci>mekstar</ci>
                                       </apply>
                                       <ci>mekstarstar</ci>
                                    </apply>
                                    <ci>mekstarmekpase</ci>
                                 </apply>
                                 <ci>mekstarstarmekpase</ci>
                              </apply>
                              <ci>mekmosstar</ci>
                           </apply>
                           <ci>mekstarmosstar</ci>
                        </apply>
                        <ci>mapkmekstarstar</ci>
                     </apply>
                     <ci>mapkstarmekstarstar</ci>
                  </apply>
                  <ci>mosstar</ci>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d3</ci>
                     <ci>k3</ci>
                  </apply>
                  <ci>mekmosstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mekstar" name="mekstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mekstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mekstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phosphorylated MAPKK</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="mekstar_mekstar" initial_value="0" name="mekstar" public_interface="out" units="micromolar"/>
      <variable name="a4" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mekpasetot" public_interface="in" units="micromolar"/>
      <variable name="mekstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="mekstarstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="d4" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k3" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekmosstar" public_interface="in" units="micromolar"/>
      <variable name="k6" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="d5" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekstarmosstar" public_interface="in" units="micromolar"/>
      <variable name="a5" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mosstar" public_interface="in" units="micromolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <plus/>
                  <apply>
                     <times/>
                     <apply>
                        <minus/>
                        <ci>a4</ci>
                     </apply>
                     <ci>mekstar</ci>
                     <apply>
                        <minus/>
                        <apply>
                           <minus/>
                           <ci>mekpasetot</ci>
                           <ci>mekstarmekpase</ci>
                        </apply>
                        <ci>mekstarstarmekpase</ci>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <ci>d4</ci>
                     <ci>mekstarmekpase</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>k3</ci>
                     <ci>mekmosstar</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>k6</ci>
                     <ci>mekstarstarmekpase</ci>
                  </apply>
                  <apply>
                     <times/>
                     <ci>d5</ci>
                     <ci>mekstarmosstar</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>a5</ci>
                  <ci>mekstar</ci>
                  <ci>mosstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mekstarmekpase" name="mekstarmekpase">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mekstarmekpase">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mekstarmekpase</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phopsphorylated MAPKK-MAPKK phosphorylase complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable initial_value="0" name="mekstarmekpase" public_interface="out" units="micromolar"/>
      <variable name="time" public_interface="in" units="second"/>
      <variable name="a4" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="d4" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k4" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekstar" public_interface="in" units="micromolar"/>
      <variable name="mekpasetot" public_interface="in" units="micromolar"/>
      <variable name="mekstarstarmekpase" public_interface="in" units="micromolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekstarmekpase</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a4</ci>
                  <ci>mekstar</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <ci>mekpasetot</ci>
                        <ci>mekstarmekpase</ci>
                     </apply>
                     <ci>mekstarstarmekpase</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d4</ci>
                     <ci>k4</ci>
                  </apply>
                  <ci>mekstarmekpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mekstarmosstar" name="mekstarmosstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mekstarmosstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mekstarmosstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phosphorylated MAPKK-activated MAPKKK complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mekstarmosstar" public_interface="out" units="micromolar"/>
      <variable name="a5" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="d5" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k5" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekstar" public_interface="in" units="micromolar"/>
      <variable name="mosstar" public_interface="in" units="micromolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekstarmosstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a5</ci>
                  <ci>mekstar</ci>
                  <ci>mosstar</ci>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d5</ci>
                     <ci>k5</ci>
                  </apply>
                  <ci>mekstarmosstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mekstarstar" name="mekstarstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mekstarstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mekstarstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">biphosphorylated MAPKK</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="mekstarstar_mekstarstar" initial_value="0" name="mekstarstar" public_interface="out" units="micromolar"/>
      <variable name="k5" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekstarmosstar" public_interface="in" units="micromolar"/>
      <variable name="a6" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mekpasetot" public_interface="in" units="micromolar"/>
      <variable name="mekstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="d6" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mekstarstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="a7" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapktot" public_interface="in" units="micromolar"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="d7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="d9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="a9" public_interface="in" units="second_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekstarstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <plus/>
                  <apply>
                     <minus/>
                     <apply>
                        <plus/>
                        <apply>
                           <minus/>
                           <apply>
                              <times/>
                              <ci>k5</ci>
                              <ci>mekstarmosstar</ci>
                           </apply>
                           <apply>
                              <times/>
                              <ci>a6</ci>
                              <ci>mekstarstar</ci>
                              <apply>
                                 <minus/>
                                 <apply>
                                    <minus/>
                                    <ci>mekpasetot</ci>
                                    <ci>mekstarmekpase</ci>
                                 </apply>
                                 <ci>mekstarstarmekpase</ci>
                              </apply>
                           </apply>
                        </apply>
                        <apply>
                           <times/>
                           <ci>d6</ci>
                           <ci>mekstarstarmekpase</ci>
                        </apply>
                     </apply>
                     <apply>
                        <times/>
                        <ci>a7</ci>
                        <ci>mekstarstar</ci>
                        <apply>
                           <minus/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <apply>
                                    <minus/>
                                    <apply>
                                       <minus/>
                                       <apply>
                                          <minus/>
                                          <ci>mapktot</ci>
                                          <ci>mapkstar</ci>
                                       </apply>
                                       <ci>mapkstarstar</ci>
                                    </apply>
                                    <ci>mapkstarmapkpase</ci>
                                 </apply>
                                 <ci>mapkstarstarmapkpase</ci>
                              </apply>
                              <ci>mapkmekstarstar</ci>
                           </apply>
                           <ci>mapkstarmekstarstar</ci>
                        </apply>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <apply>
                        <plus/>
                        <ci>d7</ci>
                        <ci>k7</ci>
                     </apply>
                     <ci>mapkmekstarstar</ci>
                  </apply>
                  <apply>
                     <times/>
                     <apply>
                        <plus/>
                        <ci>d9</ci>
                        <ci>k9</ci>
                     </apply>
                     <ci>mapkstarmekstarstar</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>a9</ci>
                  <ci>mapkstar</ci>
                  <ci>mekstarstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mekstarstarmekpase" name="mekstarstarmekpase">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mekstarstarmekpase">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mekstarstarmekpase</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">biphosphorylated MAPKK-MAPKK phosphatase complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF>
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mekstarstarmekpase" public_interface="out" units="micromolar"/>
      <variable name="a6" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mekpasetot" public_interface="in" units="micromolar"/>
      <variable name="mekstarmekpase" public_interface="in" units="micromolar"/>
      <variable name="d6" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k6" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mekstarstarmekpase</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a6</ci>
                  <ci>mekstarstar</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <ci>mekpasetot</ci>
                        <ci>mekstarmekpase</ci>
                     </apply>
                     <ci>mekstarstarmekpase</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d6</ci>
                     <ci>k6</ci>
                  </apply>
                  <ci>mekstarstarmekpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapk" name="mapk">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapk">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapk</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">MAPK</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="mapk_mapk" initial_value="1.2" name="mapk" public_interface="out" units="micromolar"/>
      <variable name="a7" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapktot" public_interface="in" units="micromolar"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <variable name="d7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k8" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapk</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <ci>a7</ci>
                  </apply>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <apply>
                           <minus/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <apply>
                                    <minus/>
                                    <ci>mapktot</ci>
                                    <ci>mapkstar</ci>
                                 </apply>
                                 <ci>mapkstarstar</ci>
                              </apply>
                              <ci>mapkstarmapkpase</ci>
                           </apply>
                           <ci>mapkstarstarmapkpase</ci>
                        </apply>
                        <ci>mapkmekstarstar</ci>
                     </apply>
                     <ci>mapkstarmekstarstar</ci>
                  </apply>
                  <ci>mekstarstar</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>d7</ci>
                  <ci>mapkmekstarstar</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>k8</ci>
                  <ci>mapkstarmapkpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkmekstarstar" name="mapkmekstarstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkmekstarstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkmekstarstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">MAPK-biphosphorylated MAPKK complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mapkmekstarstar" public_interface="out" units="micromolar"/>
      <variable name="mapktot" public_interface="in" units="micromolar"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <variable name="d7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="a7" public_interface="in" units="second_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkmekstarstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a7</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <apply>
                           <minus/>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <apply>
                                    <minus/>
                                    <ci>mapktot</ci>
                                    <ci>mapkstar</ci>
                                 </apply>
                                 <ci>mapkstarstar</ci>
                              </apply>
                              <ci>mapkstarmapkpase</ci>
                           </apply>
                           <ci>mapkstarstarmapkpase</ci>
                        </apply>
                        <ci>mapkmekstarstar</ci>
                     </apply>
                     <ci>mapkstarmekstarstar</ci>
                  </apply>
                  <ci>mekstarstar</ci>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d7</ci>
                     <ci>k7</ci>
                  </apply>
                  <ci>mapkmekstarstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkstar" name="mapkstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phosphorylated MAPK</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="mapkstar_mapkstar" initial_value="0" name="mapkstar" public_interface="out" units="micromolar"/>
      <variable name="k7" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mapkmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="a8" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapkpasetot" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="d8" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="a9" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <variable name="d9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <variable name="k10" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkstar</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <minus/>
                  <apply>
                     <plus/>
                     <apply>
                        <minus/>
                        <apply>
                           <times/>
                           <ci>k7</ci>
                           <ci>mapkmekstarstar</ci>
                        </apply>
                        <apply>
                           <times/>
                           <ci>a8</ci>
                           <ci>mapkstar</ci>
                           <apply>
                              <minus/>
                              <apply>
                                 <minus/>
                                 <ci>mapkpasetot</ci>
                                 <ci>mapkstarmapkpase</ci>
                              </apply>
                              <ci>mapkstarstarmapkpase</ci>
                           </apply>
                        </apply>
                     </apply>
                     <apply>
                        <times/>
                        <ci>d8</ci>
                        <ci>mapkstarmapkpase</ci>
                     </apply>
                  </apply>
                  <apply>
                     <times/>
                     <ci>a9</ci>
                     <ci>mapkstar</ci>
                     <ci>mekstarstar</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>d9</ci>
                  <ci>mapkstarmekstarstar</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>k10</ci>
                  <ci>mapkstarstarmapkpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkstarmekstarstar" name="mapkstarmekstarstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkstarmekstarstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkstarmekstarstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phosphorylated MAPK-biphosphorylated MAPKK complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mapkstarmekstarstar" public_interface="out" units="micromolar"/>
      <variable name="a9" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="d9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkstarmekstarstar</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a9</ci>
                  <ci>mapkstar</ci>
                  <ci>mekstarstar</ci>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d9</ci>
                     <ci>k9</ci>
                  </apply>
                  <ci>mapkstarmekstarstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkstarstar" name="mapkstarstar">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkstarstar">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkstarstar</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">biphosphorylated MAPK</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable cmeta:id="mapkstarstar_mapkstarstar" initial_value="0" name="mapkstarstar" public_interface="out" units="micromolar"/>
      <variable name="a10" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapkpasetot" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="d10" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k9" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mekstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmekstarstar" public_interface="in" units="micromolar"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkstarstar</ci>
            </apply>
            <apply>
               <plus/>
               <apply>
                  <times/>
                  <apply>
                     <minus/>
                     <ci>a10</ci>
                  </apply>
                  <ci>mapkstarstar</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <ci>mapkpasetot</ci>
                        <ci>mapkstarmapkpase</ci>
                     </apply>
                     <ci>mapkstarstarmapkpase</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <ci>d10</ci>
                  <ci>mapkstarstarmapkpase</ci>
               </apply>
               <apply>
                  <times/>
                  <ci>k9</ci>
                  <ci>mapkstarmekstarstar</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkstarmapkpase" name="mapkstarmapkpase">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkstarmapkpase">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkstarmapkpase</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">phosphorylated MAPK-MAPK phosphatase complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mapkstarmapkpase" public_interface="out" units="micromolar"/>
      <variable name="a8" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapkstar" public_interface="in" units="micromolar"/>
      <variable name="mapkpasetot" public_interface="in" units="micromolar"/>
      <variable name="mapkstarstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="d8" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k8" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkstarmapkpase</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a8</ci>
                  <ci>mapkstar</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <ci>mapkpasetot</ci>
                        <ci>mapkstarmapkpase</ci>
                     </apply>
                     <ci>mapkstarstarmapkpase</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d8</ci>
                     <ci>k8</ci>
                  </apply>
                  <ci>mapkstarmapkpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <component cmeta:id="mapkstarstarmapkpase" name="mapkstarstarmapkpase">
    <rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
      <rdf:Description rdf:about="#mapkstarstarmapkpase">
        <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">mapkstarstarmapkpase</dc:title>
        <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">biphosphorylated MAPK-MAPK phosphatase complex</dcterms:alternative>  
      </rdf:Description>
    </rdf:RDF> 
      <variable name="time" public_interface="in" units="second"/>
      <variable initial_value="0" name="mapkstarstarmapkpase" public_interface="out" units="micromolar"/>
      <variable name="a10" public_interface="in" units="second_order_rate_constant_units"/>
      <variable name="mapkstarstar" public_interface="in" units="micromolar"/>
      <variable name="mapkpasetot" public_interface="in" units="micromolar"/>
      <variable name="mapkstarmapkpase" public_interface="in" units="micromolar"/>
      <variable name="d10" public_interface="in" units="first_order_rate_constant_units"/>
      <variable name="k10" public_interface="in" units="first_order_rate_constant_units"/>
      <math xmlns="http://www.w3.org/1998/Math/MathML">
         <apply>
            <eq/>
            <apply>
               <diff/>
               <bvar>
                  <ci>time</ci>
               </bvar>
               <ci>mapkstarstarmapkpase</ci>
            </apply>
            <apply>
               <minus/>
               <apply>
                  <times/>
                  <ci>a10</ci>
                  <ci>mapkstarstar</ci>
                  <apply>
                     <minus/>
                     <apply>
                        <minus/>
                        <ci>mapkpasetot</ci>
                        <ci>mapkstarmapkpase</ci>
                     </apply>
                     <ci>mapkstarstarmapkpase</ci>
                  </apply>
               </apply>
               <apply>
                  <times/>
                  <apply>
                     <plus/>
                     <ci>d10</ci>
                     <ci>k10</ci>
                  </apply>
                  <ci>mapkstarstarmapkpase</ci>
               </apply>
            </apply>
         </apply>
      </math>
   </component>
   
   <connection>
      <map_components component_1="environment" component_2="mos"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mos"/>
      <map_variables variable_1="a1" variable_2="a1"/>
      <map_variables variable_1="d1" variable_2="d1"/>
      <map_variables variable_1="k2" variable_2="k2"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mos"/>
      <map_variables variable_1="mostot" variable_2="mostot"/>
      <map_variables variable_1="e1tot" variable_2="e1tot"/>
   </connection>
   <connection>
      <map_components component_1="mosstar" component_2="mos"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="mose1" component_2="mos"/>
      <map_variables variable_1="mose1" variable_2="mose1"/>
   </connection>
   <connection>
      <map_components component_1="mosstare2" component_2="mos"/>
      <map_variables variable_1="mosstare2" variable_2="mosstare2"/>
   </connection>
   <connection>
      <map_components component_1="mekmosstar" component_2="mos"/>
      <map_variables variable_1="mekmosstar" variable_2="mekmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mos"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mose1"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mose1"/>
      <map_variables variable_1="a1" variable_2="a1"/>
      <map_variables variable_1="d1" variable_2="d1"/>
      <map_variables variable_1="k1" variable_2="k1"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mose1"/>
      <map_variables variable_1="mostot" variable_2="mostot"/>
      <map_variables variable_1="e1tot" variable_2="e1tot"/>
   </connection>
   <connection>
      <map_components component_1="mosstar" component_2="mose1"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
      <map_variables variable_1="mose1" variable_2="mose1"/>
   </connection>
   <connection>
      <map_components component_1="mosstare2" component_2="mose1"/>
      <map_variables variable_1="mosstare2" variable_2="mosstare2"/>
   </connection>
   <connection>
      <map_components component_1="mekmosstar" component_2="mose1"/>
      <map_variables variable_1="mekmosstar" variable_2="mekmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mose1"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mosstar"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mosstar"/>
      <map_variables variable_1="a2" variable_2="a2"/>
      <map_variables variable_1="d2" variable_2="d2"/>
      <map_variables variable_1="k1" variable_2="k1"/>
      <map_variables variable_1="a3" variable_2="a3"/>
      <map_variables variable_1="d3" variable_2="d3"/>
      <map_variables variable_1="k3" variable_2="k3"/>
      <map_variables variable_1="a5" variable_2="a5"/>
      <map_variables variable_1="d5" variable_2="d5"/>
      <map_variables variable_1="k5" variable_2="k5"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mosstar"/>
      <map_variables variable_1="mektot" variable_2="mektot"/>
      <map_variables variable_1="e2tot" variable_2="e2tot"/>
   </connection>
   <connection>
      <map_components component_1="mosstare2" component_2="mosstar"/>
      <map_variables variable_1="mosstare2" variable_2="mosstare2"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekmosstar" component_2="mosstar"/>
      <map_variables variable_1="mekmosstar" variable_2="mekmosstar"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstar" component_2="mosstar"/>
      <map_variables variable_1="mekstar" variable_2="mekstar"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstar" component_2="mosstar"/>
      <map_variables variable_1="mekstarstar" variable_2="mekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmekpase" component_2="mosstar"/>
      <map_variables variable_1="mekstarmekpase" variable_2="mekstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstarmekpase" component_2="mosstar"/>
      <map_variables variable_1="mekstarstarmekpase" variable_2="mekstarstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mosstar"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="mapkmekstarstar" component_2="mosstar"/>
      <map_variables variable_1="mapkmekstarstar" variable_2="mapkmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mapkstarmekstarstar" component_2="mosstar"/>
      <map_variables variable_1="mapkstarmekstarstar" variable_2="mapkstarmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mosstare2"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mosstare2"/>
      <map_variables variable_1="a2" variable_2="a2"/>
      <map_variables variable_1="d2" variable_2="d2"/>
      <map_variables variable_1="k2" variable_2="k2"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mosstare2"/>
      <map_variables variable_1="e2tot" variable_2="e2tot"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mek"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mek"/>
      <map_variables variable_1="a3" variable_2="a3"/>
      <map_variables variable_1="d3" variable_2="d3"/>
      <map_variables variable_1="k4" variable_2="k4"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mek"/>
      <map_variables variable_1="mektot" variable_2="mektot"/>
   </connection>
   <connection>
      <map_components component_1="mekstar" component_2="mek"/>
      <map_variables variable_1="mekstar" variable_2="mekstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstar" component_2="mek"/>
      <map_variables variable_1="mekstarstar" variable_2="mekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmekpase" component_2="mek"/>
      <map_variables variable_1="mekstarmekpase" variable_2="mekstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstarmekpase" component_2="mek"/>
      <map_variables variable_1="mekstarstarmekpase" variable_2="mekstarstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mapkstarmekstarstar" component_2="mek"/>
      <map_variables variable_1="mapkstarmekstarstar" variable_2="mapkstarmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mekmosstar" component_2="mek"/>
      <map_variables variable_1="mekmosstar" variable_2="mekmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mek"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mapkmekstarstar" component_2="mek"/>
      <map_variables variable_1="mapkmekstarstar" variable_2="mapkmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mosstar" component_2="mek"/>
      <map_variables variable_1="mosstar" variable_2="mosstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mekmosstar"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mekmosstar"/>
      <map_variables variable_1="a3" variable_2="a3"/>
      <map_variables variable_1="d3" variable_2="d3"/>
      <map_variables variable_1="k3" variable_2="k3"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mekmosstar"/>
      <map_variables variable_1="mektot" variable_2="mektot"/>
   </connection>
   <connection>
      <map_components component_1="mekstar" component_2="mekmosstar"/>
      <map_variables variable_1="mekstar" variable_2="mekstar"/>
      <map_variables variable_1="mekmosstar" variable_2="mekmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstar" component_2="mekmosstar"/>
      <map_variables variable_1="mekstarstar" variable_2="mekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmekpase" component_2="mekmosstar"/>
      <map_variables variable_1="mekstarmekpase" variable_2="mekstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstarmekpase" component_2="mekmosstar"/>
      <map_variables variable_1="mekstarstarmekpase" variable_2="mekstarstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mekmosstar"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
   </connection>
   <connection>
      <map_components component_1="mapkmekstarstar" component_2="mekmosstar"/>
      <map_variables variable_1="mapkmekstarstar" variable_2="mapkmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="mapkstarmekstarstar" component_2="mekmosstar"/>
      <map_variables variable_1="mapkstarmekstarstar" variable_2="mapkstarmekstarstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mekstar"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mekstar"/>
      <map_variables variable_1="a4" variable_2="a4"/>
      <map_variables variable_1="d4" variable_2="d4"/>
      <map_variables variable_1="k3" variable_2="k3"/>
      <map_variables variable_1="a5" variable_2="a5"/>
      <map_variables variable_1="d5" variable_2="d5"/>
      <map_variables variable_1="k6" variable_2="k6"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mekstar"/>
      <map_variables variable_1="mekpasetot" variable_2="mekpasetot"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmekpase" component_2="mekstar"/>
      <map_variables variable_1="mekstarmekpase" variable_2="mekstarmekpase"/>
      <map_variables variable_1="mekstar" variable_2="mekstar"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstarmekpase" component_2="mekstar"/>
      <map_variables variable_1="mekstarstarmekpase" variable_2="mekstarstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="mekstarmosstar" component_2="mekstar"/>
      <map_variables variable_1="mekstarmosstar" variable_2="mekstarmosstar"/>
      <map_variables variable_1="mekstar" variable_2="mekstar"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mekstarmekpase"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mekstarmekpase"/>
      <map_variables variable_1="a4" variable_2="a4"/>
      <map_variables variable_1="d4" variable_2="d4"/>
      <map_variables variable_1="k4" variable_2="k4"/>
   </connection>
   <connection>
      <map_components component_1="mekstarstarmekpase" component_2="mekstarmekpase"/>
      <map_variables variable_1="mekstarstarmekpase" variable_2="mekstarstarmekpase"/>
      <map_variables variable_1="mekstarmekpase" variable_2="mekstarmekpase"/>
   </connection>
   <connection>
      <map_components component_1="total_concs" component_2="mekstarmekpase"/>
      <map_variables variable_1="mekpasetot" variable_2="mekpasetot"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mekstarmosstar"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
      <map_components component_1="rate_constants" component_2="mekstarmosstar"/>
      <map_variables variable_1="a5" variable_2="a5"/>
      <map_variables variable_1="d5" variable_2="d5"/>
      <map_variables variable_1="k5" variable_2="k5"/>
   </connection>
   <connection>
      <map_components component_1="environment" component_2="mekstarstar"/>
      <map_variables variable_1="time" variable_2="time"/>
   </connection>
   <connection>
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