Rendering of the source text

<?xml version='1.0' encoding='utf-8'?>
<!--  FILE :  dempsher_model_1984.xml

CREATED :  28th June 2007

LAST MODIFIED : 28th June 2007

AUTHOR :  Catherine Lloyd
          Bioengineering Institute
          The University of Auckland
          
MODEL STATUS :  This model conforms to the CellML 1.1 Specification.

DESCRIPTION :  This file contains a CellML description of Dempsher et al.'s 1984 mathematical model of ACTH-stimulated cortisol secretion.

CHANGES:  
  
--><model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#" xmlns:ns7="http://www.cellml.org/metadata/simulation/1.0#" cmeta:id="dempsher_model_1984" name="dempsher_gann_phair_model_1984_version01">

<documentation xmlns="http://cellml.org/tmp-documentation">

<article>
  <articleinfo>
  <title>A mechanistic model of ACTH-stimulated cortisol secretion</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 model has been edited to correct dimensional errors and checked for other problems. It runs in COR and OpenCell but whether it replicates experimental results is yet to be determined.</para>
<para>
ValidateCellML confirms this model to be valid CellML but detects units inconsistencies.
          </para>
			</section>
  <sect1 id="sec_structure">
  <title>Model Structure</title>

<para>
Advances in the study of cortisol biosynthesis indicate that adrenocorticotropin (ACTH) stimulates steroid secretion by facilitating the delivery of free cholesterol to the side chain cleavage (scc) enzyme.  ACTH binds to one or more specific receptors in the adrenocortical cell membrane (represented by A and B in the figure below) which has the effect of activating adenylate cyclase (ACase).  The cytosolic concentration of adenosine 3,5-cyclic monophosphate (cAMP) increases, in turn a) activating cholesterol ester (CE) hydrolase, which catalyses the conversion of cholesterol ester into free cholesterol, and b) facilitating the transfer of cholesterol within the mitochondrion to a site accessible to the scc enzyme.  Furthermore, low density lipoprotein receptor-mediated uptake of plasma cholesterol together with cytosolic cholesterol synthesis provide substrate for steroid synthesis, and both these processes can be controlled by an intracellular pool of cholesterol.
</para>

<para>
In their 1984 publication, Dempsher <emphasis>et al.</emphasis> describe all these physiological phenomena in a mathematical model of ACTH-stimulated cortisol secretion (the complete original paper reference is cited below).  Steps in the biosynthetic pathway are described using first-order linear differential equations, and the results of the model simulations were compared, and were consistent with, experimental data.   

The corticotropin-releasing hormone (CRH) is synthesised in the hypothalamus and is carried to the anterior pituitary gland where it stimulates cells to produce adrenocorticotrophic hormone (ACTH).  In turn, ACTH stimulates the synthesis and secretion of cortisol (F).  Cortisol exerts a negative feedback effect on the ACTH secretion in the pituitary and also suppresses CRH synthesis in the hypothalamus.  In addition, there is also a negative feedback effect of ACTH on the secretion of CRH.  Therefore the entire process can be thought of as a self-regulating system, as summarised in <xref linkend="fig_reaction_diagram"/> below).
</para>

<para>
A mechanistic model of ACTH-stimulated cortisol secretion, D.P. Dempsher, D.S. Gann, and R.D. Phair, 1984, 
            <emphasis>American Journal of Physiology</emphasis>
          , 246, R587-R596.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=6326602&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 6326602</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="dempsher_gann_phair_1984.png"/>
  </imageobject>
</mediaobject>
<caption>Schematic diagram of the model describing the effects of ACTH on cortisol secretion. (note that ECF represents the extracellular fluid).</caption>
</informalfigure>

</sect1>
</article>
</documentation> 



  
  <units name="nanomole">
    <unit units="mole" prefix="nano"/>
  </units>  

  <units name="nanomolar">
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    <unit units="nanomolar" exponent="-1"/>
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    <variable units="flux" name="Vdsm" initial_value="10.0"/>
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                <geq/>
                <ci> time </ci>
                <cn cellml:units="minute"> 35.0 </cn>
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                <ci> time </ci>
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              </apply>
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          </piece>
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            <cn cellml:units="picomolar"> 12.0 </cn>
          </otherwise>
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    </math> 
  </component>

  <component name="IS">
     
    <variable units="nmol_g" public_interface="out" cmeta:id="IS_IS" name="IS"/> 
    
    <variable units="nmol_g" name="Crpt" initial_value="3.0"/>
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    <variable units="nmol_g" name="Kd" initial_value="2.11"/>
    <variable units="dimensionless" name="n" initial_value="4.0"/>
    
    <variable units="nmol_g" public_interface="in" name="cAMP"/>
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        <apply>
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            <ci> Crpt </ci>
            <apply>
              <power/>
              <ci> cAMP </ci>
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            <plus/>
            <apply>
              <power/>
              <ci> Kd </ci>
              <ci> n </ci>
            </apply>
            <apply>
              <power/>
              <ci> cAMP </ci>
              <ci> n </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 

<!-- this equation was added to the original model by a later published paper.  It has now been replaced by the original parameter value of '80' 
    
      <apply id="K_calculation"><eq />
        <ci> K </ci>
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            <apply><and />
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                <ci> time </ci>
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              </apply>
            </apply>
          </piece>
        </piecewise>
      </apply> -->
   
    </math> 
  </component>
  
  <component cmeta:id="V" name="V">
     
    <variable units="flux" public_interface="out" cmeta:id="V_V" name="V" initial_value="11.3"/> 
    
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    <variable units="nmol_g" public_interface="in" name="IS"/>
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    <variable units="flux" public_interface="out" cmeta:id="W_W" name="W" initial_value="10.0"/> 
    
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              <ci> CHOC </ci>
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            <times/> 
            <ci> U </ci>
            <ci> W </ci>
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        </apply>  
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    <variable units="first_order_rate_constant" public_interface="in" name="Lmtr"/>
    <variable units="first_order_rate_constant" public_interface="in" name="Kmtr"/>
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    <variable units="nmol_g" public_interface="out" cmeta:id="CHOM_CHOM" name="CHOM" initial_value="11.3"/>

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    <variable units="first_order_rate_constant" public_interface="in" name="Kcf"/>
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    <variable units="first_order_rate_constant" public_interface="in" name="Kmtr"/>
    <variable units="nmol_g" public_interface="in" name="CHOC"/>
    <variable units="nmol_g" public_interface="in" name="CHON"/>
    <variable units="nmol_g" public_interface="in" name="CHOL"/>
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          <ci> CHOM </ci> 
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            <apply>
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            <apply>
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              <ci> Kcf </ci>
              <ci> CHOL </ci>
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          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> Lmtr </ci>
              <ci> CHOM </ci>
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            <apply>
              <times/>
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            <apply>
              <times/>
              <ci> Kfor </ci>
              <ci> CHOM </ci>
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        </apply>  
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  <component cmeta:id="CHOL" name="CHOL">
     
    <variable units="nmol_g" public_interface="out" cmeta:id="CHOL_CHOL" name="CHOL" initial_value="3000.0"/>

    <variable units="first_order_rate_constant" public_interface="in" name="Kcb"/>
    <variable units="first_order_rate_constant" public_interface="in" name="Kcf"/>
    <variable units="nmol_g" public_interface="in" name="CHOM"/>
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            <ci>time</ci>
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            <times/>
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            <ci> CHOM </ci>
          </apply>
          <apply>
            <times/>
            <ci> Kcf </ci>
            <ci> CHOL </ci>
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    <variable units="first_order_rate_constant" public_interface="out" name="Kmtr" initial_value="0.446"/> 
    
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    <variable units="nmol_g" public_interface="in" name="IS"/>
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    <variable units="nmol_g" public_interface="in" name="CHOM"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
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          </bvar> 
          <ci> CHON </ci> 
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        <apply>
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            <ci> Kfor </ci>
            <ci> CHOM </ci>
	      </apply>
          <apply>
            <plus/>
            <apply>
              <times/>
              <ci> Kbac </ci>
              <ci> CHON </ci>
            </apply>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> Vm </ci>
                <ci> CHON </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Km </ci>
                <ci> CHON </ci>
              </apply>
            </apply>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>

  <component cmeta:id="PREG" name="PREG">
     
    <variable units="nmol_g" public_interface="out" cmeta:id="PREG_PREG" name="PREG" initial_value="6.56"/> 
    
    <variable units="flux" public_interface="in" name="Vmptr"/>
    <variable units="nmol_g" public_interface="in" name="Kmptr"/>
    <variable units="flux" public_interface="in" name="Vm"/>
    <variable units="nmol_g" public_interface="in" name="Km"/>
    <variable units="nmol_g" public_interface="in" name="CHON"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
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        <apply>
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            <divide/>
            <apply>
              <times/>
              <ci> Vm </ci>
              <ci> CHON </ci>
            </apply>
            <apply>
              <plus/>
              <ci> Km </ci>
              <ci> CHON </ci>
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          </apply>
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            <divide/>
            <apply>
              <times/>
              <ci> Vmptr </ci>
              <ci> PREG </ci>
            </apply>
            <apply>
              <plus/>
              <ci> Kmptr </ci>
              <ci> PREG </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    </math> 
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  <component cmeta:id="PRO" name="PRO">
     
    <variable units="nmol_g" public_interface="out" cmeta:id="PRO_PRO" name="PRO" initial_value="0.64"/> 
    
    <variable units="dimensionless" name="HA" initial_value="0.5"/>

    <variable units="flux" public_interface="in" name="Vmptr"/>
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    <variable units="first_order_rate_constant" public_interface="in" name="AH"/>
    <variable units="nmol_g" public_interface="in" name="PREG"/>
    <variable units="minute" public_interface="in" name="time"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
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        <apply>
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            <ci>time</ci>
          </bvar> 
          <ci> PRO </ci> 
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        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> HA </ci>
            <apply>
              <divide/>
              <apply>
                <times/>
                <ci> Vmptr </ci>
                <ci> PREG </ci>
              </apply>
              <apply>
                <plus/>
                <ci> Kmptr </ci>
                <ci> PREG </ci>
              </apply>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> AH </ci>
            <ci> PRO </ci>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>

  <component cmeta:id="HYPR" name="HYPR">
     
    <variable units="nmol_g" public_interface="out" cmeta:id="HYPR_HYPR" name="HYPR" initial_value="0.64"/> 
    
    <variable units="first_order_rate_constant" public_interface="in" name="HY"/>
    <variable units="first_order_rate_constant" public_interface="in" name="AH"/>
    <variable units="nmol_g" public_interface="in" name="PRO"/>
    <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> HYPR </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> AH </ci>
            <ci> PRO </ci>
          </apply>
          <apply>
            <times/>
            <ci> HY </ci>
            <ci> HYPR </ci>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>

  <component cmeta:id="CORT" name="CORT">
     
    <variable units="nmol_g" cmeta:id="CORT_CORT" name="CORT" initial_value="5.2"/> 
    
    <variable units="first_order_rate_constant" name="LH" initial_value="0.724"/>
    <variable units="flux" cmeta:id="CORT_LH_CORT" name="LH_CORT"/>

    <variable units="first_order_rate_constant" public_interface="in" name="HY"/>
    <variable units="nmol_g" public_interface="in" name="HYPR"/>
    <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> CORT </ci> 
        </apply>
        <apply>
          <minus/>
          <apply>
            <times/>
            <ci> HY </ci>
            <ci> HYPR </ci>
          </apply>
          <apply>
            <times/>
            <ci> LH </ci>
            <ci> CORT </ci>
          </apply>
        </apply>  
      </apply>

      <apply>
        <eq/> 
        <ci> LH_CORT </ci> 
        <apply>
          <times/>
          <ci> LH </ci>
          <ci> CORT </ci>
        </apply>  
      </apply>  
    </math> 
  </component>
  
  <component name="model_parameters">
    <variable units="first_order_rate_constant" public_interface="out" name="Lmtr" initial_value="1.65"/>
    <variable units="first_order_rate_constant" public_interface="out" name="Kbac" initial_value="10.0"/>
    <variable units="first_order_rate_constant" public_interface="out" name="Kcb" initial_value="0.01"/>
    <variable units="first_order_rate_constant" public_interface="out" name="Kcf" initial_value="0.00033"/>
    <variable units="flux" public_interface="out" name="Vm" initial_value="1890.0"/>
    <variable units="nmol_g" public_interface="out" name="Km" initial_value="270.0"/>
    <variable units="flux" public_interface="out" name="Vmptr" initial_value="500.0"/>
    <variable units="nmol_g" public_interface="out" name="Kmptr" initial_value="150.0"/>
    <variable units="first_order_rate_constant" public_interface="out" name="AH" initial_value="16.4"/>
    <variable units="first_order_rate_constant" public_interface="out" name="HY" initial_value="16.4"/>
  </component> 

  <connection>
    <map_components component_2="environment" component_1="cAMP"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="IS"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>
  
  <connection>
    <map_components component_2="environment" component_1="V"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="W"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="CHOC"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="CHOM"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="CHOL"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="Kmtr"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="Kfor"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="CHON"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="PREG"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="PRO"/>
    <map_variables variable_2="time" variable_1="time"/>
  </connection>

  <connection>
    <map_components component_2="environment" component_1="HYPR"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="environment" component_1="CORT"/>
    <map_variables variable_2="time" variable_1="time"/>
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  <connection>
    <map_components component_2="IS" component_1="cAMP"/>
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    <map_variables variable_2="CHOM" variable_1="CHOM"/>
    <map_variables variable_2="CHOC" variable_1="CHOC"/>
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  <connection>
    <map_components component_2="CHOC" component_1="Kmtr"/>
    <map_variables variable_2="Kmtr" variable_1="Kmtr"/>
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  <connection>
    <map_components component_2="V" component_1="CHOC"/>
    <map_variables variable_2="V" variable_1="V"/>
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  <connection>
    <map_components component_2="model_parameters" component_1="CHOC"/>
    <map_variables variable_2="Lmtr" variable_1="Lmtr"/>
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  <connection>
    <map_components component_2="CHOM" component_1="CHON"/>
    <map_variables variable_2="CHOM" variable_1="CHOM"/>
    <map_variables variable_2="CHON" variable_1="CHON"/>
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  <connection>
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    <map_variables variable_2="CHOM" variable_1="CHOM"/>
    <map_variables variable_2="CHOL" variable_1="CHOL"/>
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  <connection>
    <map_components component_2="Kfor" component_1="CHOM"/>
    <map_variables variable_2="Kfor" variable_1="Kfor"/>
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  <connection>
    <map_components component_2="CHOM" component_1="Kmtr"/>
    <map_variables variable_2="Kmtr" variable_1="Kmtr"/>
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    <map_components component_2="model_parameters" component_1="CHOM"/>
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    <map_variables variable_2="Kbac" variable_1="Kbac"/>
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  <connection>
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<rdf:RDF>
  <rdf:Bag rdf:about="rdf:#d7c55d63-141d-4a11-8938-07be8c8a0cb7">
    <rdf:li>cortisol</rdf:li>
    <rdf:li>HPA axis</rdf:li>
    <rdf:li>endocrine</rdf:li>
  </rdf:Bag>
  <rdf:Seq rdf:about="rdf:#a4d925c2-b101-406f-b1dc-aa6211b52eda">
    <rdf:li rdf:resource="rdf:#02d23f7a-075f-4b83-b36d-d7cf168d6ea6"/>
    <rdf:li rdf:resource="rdf:#594c3491-ad57-40cf-aafa-81dfb06012d1"/>
    <rdf:li rdf:resource="rdf:#4bed82da-10ad-41c9-adbf-f9c32ccd872e"/>
  </rdf:Seq>
  <rdf:Description rdf:about="rdf:#95863279-64bc-473f-a01c-e5c695e29c7d">
    <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="rdf:#7ebd2478-51d9-48d2-bf07-664fc00266ea">
    <vCard:ORG rdf:resource="rdf:#a3e955af-d295-435d-9a04-98c4d4b7d2fd"/>
    <vCard:EMAIL rdf:resource="rdf:#95863279-64bc-473f-a01c-e5c695e29c7d"/>
    <vCard:N rdf:resource="rdf:#3f0e9044-0db6-4831-9381-91fb8593d8fd"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#d357af8c-2834-4bd6-a1d7-9fa581858722">
    <dcterms:modified rdf:resource="rdf:#b60dd978-75a6-4700-8a10-6016836a5188"/>
    <rdf:value>The model has been curated further.  Using COR the units were made consistent and one equation was fixed.  The model still can't perfectly recreate the published results in COR though.  I'm waiting for Alan to fix a bug in COR and then I'll try again.</rdf:value>
    <cmeta:modifier rdf:resource="rdf:#d6d1654d-792a-49b6-b163-eae8ed1fc376"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#fcea56f3-b232-4dae-98ad-b78ea38d7f9e">
    <dc:creator rdf:resource="rdf:#d43c8b12-aba6-40fb-b46c-e207abd4fec4"/>
    <rdf:value>This is the CellML description of Dempsher et al.'s 1984 mathematical model of ACTH-stimulated cortisol secretion.</rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="#IS">
    <dcterms:alternative>intracellular signal</dcterms:alternative>
    <dc:title>IS</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#HYPR">
    <dcterms:alternative>17alpha hydroxyprogesterone</dcterms:alternative>
    <dc:title>HYPR</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="">
    <dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
    <cmeta:comment rdf:resource="rdf:#ac55def9-9839-4c88-ac6d-14f1f4dc2eef"/>
    <dcterms:created rdf:resource="rdf:#4948f6f6-ad09-436e-98ee-8d5c3c2365fa"/>
    <dc:creator rdf:resource="rdf:#7ebd2478-51d9-48d2-bf07-664fc00266ea"/>
    <cmeta:modification rdf:resource="rdf:#6b2f481e-3d84-4c31-b2b5-e3e3e4369017"/>
    <cmeta:modification rdf:resource="rdf:#d357af8c-2834-4bd6-a1d7-9fa581858722"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#17ff97a0-6efa-434b-8d52-7d4175643f18">
    <dcterms:W3CDTF>1984-00-00 00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#0f509d5b-cbba-41e4-a713-70e37d13cfe8">
    <dc:title>American Journal of Physiology</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#ba223a49-ea5c-4c85-96f7-96dc3fb72691">
    <vCard:Given>D</vCard:Given>
    <vCard:Family>Dempsher</vCard:Family>
    <vCard:Other>P</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#4ec0e440-dbab-47f8-a81f-e03b1b5e8333">
    <vCard:N rdf:resource="rdf:#60ab2c1b-a832-48ab-9c1f-7266592e897b"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$hD.6n1">
    <ns7:endingValue>100</ns7:endingValue>
    <ns7:nonstandard-pointDensity>10000</ns7:nonstandard-pointDensity>
    <ns7:maximumStepSize>0.01</ns7:maximumStepSize>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#24cbbbda-149d-43c3-b7eb-554e4357cc75">
    <vCard:Given>R</vCard:Given>
    <vCard:Family>Phair</vCard:Family>
    <vCard:Other>D</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="#CORT">
    <dcterms:alternative>cortisol</dcterms:alternative>
    <dc:title>CORT</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#02d23f7a-075f-4b83-b36d-d7cf168d6ea6">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#ba223a49-ea5c-4c85-96f7-96dc3fb72691"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#76b454ef-9b0c-4d9f-af4f-30ae6e15fe1d">
    <vCard:Given>D</vCard:Given>
    <vCard:Family>Gann</vCard:Family>
    <vCard:Other>S</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="#PRO">
    <dcterms:alternative>adrenal progesterone</dcterms:alternative>
    <dc:title>PRO</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#6b2f481e-3d84-4c31-b2b5-e3e3e4369017">
    <dcterms:modified rdf:resource="rdf:#3428c244-c9b5-47d1-ba16-f5842598c0bb"/>
    <rdf:value>Change in simulation metadata&#13;
&#13;
Added cmeta:id's to some variables</rdf:value>
    <cmeta:modifier rdf:resource="rdf:#4ec0e440-dbab-47f8-a81f-e03b1b5e8333"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$gD.6n1">
    <rdf:rest rdf:resource="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/>
    <rdf:first rdf:resource="rdf:#$hD.6n1"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#594c3491-ad57-40cf-aafa-81dfb06012d1">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#76b454ef-9b0c-4d9f-af4f-30ae6e15fe1d"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#d6d1654d-792a-49b6-b163-eae8ed1fc376">
    <vCard:N rdf:resource="rdf:#7a7ea219-4d7f-4e11-a5b3-8ec76052dc6b"/>
  </rdf:Description>
  <rdf:Description rdf:about="#PREG">
    <dcterms:alternative>mitochondrial pregnolone</dcterms:alternative>
    <dc:title>PREG</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#d43c8b12-aba6-40fb-b46c-e207abd4fec4">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="#Kmtr">
    <dcterms:alternative>rate of conversion of CHOC to CHOM</dcterms:alternative>
    <dc:title>Kmtr</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#a8233bc4-89cb-4196-8ee0-f85907715798">
    <bqs:subject_type>keyword</bqs:subject_type>
    <rdf:value rdf:resource="rdf:#d7c55d63-141d-4a11-8938-07be8c8a0cb7"/>
  </rdf:Description>
  <rdf:Description rdf:about="#dempsher_model_1984">
    <ns7:simulation rdf:resource="rdf:#$fD.6n1"/>
    <dc:title>Dempsher et al.'s 1984 mathematical model of ACTH-stimulated cortisol secretion.</dc:title>
    <cmeta:bio_entity>cortisol</cmeta:bio_entity>
    <cmeta:comment rdf:resource="rdf:#fcea56f3-b232-4dae-98ad-b78ea38d7f9e"/>
    <bqs:reference rdf:resource="rdf:#084a4476-0d34-4272-be7d-10f458325c15"/>
    <bqs:reference rdf:resource="rdf:#64998e2d-6349-492f-a04a-4e18f11a9781"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#ac55def9-9839-4c88-ac6d-14f1f4dc2eef">
    <dc:creator rdf:resource="rdf:#659a95e5-73f7-406e-84ff-f560d9cece7d"/>
    <rdf:value>The model has been curated further.  Using COR the units were made consistent and one equation was fixed.  The model still can't perfectly recreate the published results though.  I'm waiting for Alan to fix a bug in COR and then I'll try again.</rdf:value>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#64998e2d-6349-492f-a04a-4e18f11a9781">
    <bqs:Pubmed_id>6326602</bqs:Pubmed_id>
    <bqs:JournalArticle rdf:resource="rdf:#925ab9e0-f346-490f-9638-d083da3f446f"/>
  </rdf:Description>
  <rdf:Description rdf:about="#Kfor">
    <dcterms:alternative>rate for the flux of cholesterol onto the side chain cleavage enzyme</dcterms:alternative>
    <dc:title>Kfor</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#V">
    <dcterms:alternative>cholesterol flux to a pool of free cholesterol</dcterms:alternative>
    <dc:title>V</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#W">
    <dcterms:alternative>flux of free cholesterol from de novo synthesis</dcterms:alternative>
    <dc:title>W</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#4bed82da-10ad-41c9-adbf-f9c32ccd872e">
    <rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person"/>
    <vCard:N rdf:resource="rdf:#24cbbbda-149d-43c3-b7eb-554e4357cc75"/>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#7a7ea219-4d7f-4e11-a5b3-8ec76052dc6b">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#a3e955af-d295-435d-9a04-98c4d4b7d2fd">
    <vCard:Orgname>The University of Auckland</vCard:Orgname>
    <vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
  </rdf:Description>
  <rdf:Description rdf:about="#cAMP">
    <dcterms:alternative>cyclic AMP</dcterms:alternative>
    <dc:title>cAMP</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#b60dd978-75a6-4700-8a10-6016836a5188">
    <dcterms:W3CDTF>2007-09-02T11:49:51+12:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#4948f6f6-ad09-436e-98ee-8d5c3c2365fa">
    <dcterms:W3CDTF>2007-06-28T00:00:00+00:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="#CHOM">
    <dcterms:alternative>mitochondrial free cholesterol made available by ACTH</dcterms:alternative>
    <dc:title>CHOM</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#CHOL">
    <dcterms:alternative>mitochondrial free cholesterol remote from the side chain cleavage enzyme</dcterms:alternative>
    <dc:title>CHOL</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#CHON">
    <dcterms:alternative>mitochondrial cholesterol close to the side chain cleavage enzyme</dcterms:alternative>
    <dc:title>CHON</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#925ab9e0-f346-490f-9638-d083da3f446f">
    <dc:creator rdf:resource="rdf:#a4d925c2-b101-406f-b1dc-aa6211b52eda"/>
    <dc:title>A mechanistic model of ACTH-stimulated cortisol secretion</dc:title>
    <bqs:volume>246</bqs:volume>
    <bqs:first_page>R587</bqs:first_page>
    <bqs:Journal rdf:resource="rdf:#0f509d5b-cbba-41e4-a713-70e37d13cfe8"/>
    <dcterms:issued rdf:resource="rdf:#17ff97a0-6efa-434b-8d52-7d4175643f18"/>
    <bqs:last_page>R596</bqs:last_page>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#60ab2c1b-a832-48ab-9c1f-7266592e897b">
    <vCard:Given>Tiwari</vCard:Given>
    <vCard:Family>Abhishek</vCard:Family>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#3f0e9044-0db6-4831-9381-91fb8593d8fd">
    <vCard:Given>Catherine</vCard:Given>
    <vCard:Family>Lloyd</vCard:Family>
    <vCard:Other>May</vCard:Other>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#659a95e5-73f7-406e-84ff-f560d9cece7d">
    <vCard:FN>Catherine Lloyd</vCard:FN>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#084a4476-0d34-4272-be7d-10f458325c15">
    <dc:subject rdf:resource="rdf:#a8233bc4-89cb-4196-8ee0-f85907715798"/>
  </rdf:Description>
  <rdf:Description rdf:about="#CHOC">
    <dcterms:alternative>free cytosolic cholesterol</dcterms:alternative>
    <dc:title>CHOC</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#3428c244-c9b5-47d1-ba16-f5842598c0bb">
    <dcterms:W3CDTF>2008-11-19T12:09:24+13:00</dcterms:W3CDTF>
  </rdf:Description>
  <rdf:Description rdf:about="rdf:#$fD.6n1">
    <ns7:boundIntervals rdf:resource="rdf:#$gD.6n1"/>
  </rdf:Description>
</rdf:RDF>
</model>