Rendering of the source text

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<!--  FILE :  macgregor_model_2005.xml

CREATED :  19th June 2007

LAST MODIFIED : 19th 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 MacGregor and Leng's 2005 mathematical model of hypothalamic control of growth hormone secretion.

CHANGES:  
  
-->
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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Modelling the Hypothalamic Control of Growth Hormone Secretion</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>
 <section id="sec_status">
    <title>Model Status</title>
    <para>
        This particular CellML model describes the full (pituitary + hypothalamic) model of the published article.  The units have been checked and are consistent, and the model runs in OpenCell and COR to replicate the published results (as shown in figure 12 of the paper).
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
Abstract: Here, we construct a mathematical model of the hypothalamic systems that control the secretion of growth hormone (GH). The work extends a recent model of the pituitary GH system, adding representations of the hypothalamic GH-releasing hormone (GHRH) and somatostatin neurones, each modelled as a single synchronised unit. An unpatterned stochastic input drives the GHRH neurones generating pulses of GHRH release that trigger GH pulses. Delayed feedback from GH results in increased somatostatin release, which inhibits both GH secretion and GHRH release, producing an overall pattern of 3-h pulses of GH secretion that is very similar to the secretory profile observed in male rats. Rather than directly stimulating somatostatin release, GH feedback triggers a priming effect, increasing releasable stores of somatostatin. Varying this priming effect to reduce the effect of GH can reproduce the less pulsatile form of GH release observed in the female rat. The model behaviour is tested by comparison with experimental observations with a range of different experimental protocols involving GHRH injections and somatostatin and GH infusion.
</para>

<para>
The complete original paper reference is cited below:
</para>

<para>
Modelling the hypothalamic control of growth hormone secretion, D. J. MacGregor and G. Leng, 2005, <emphasis>Journal of Neuroendocrinology</emphasis>, volume 17, 788-803.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=16280026&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 16280026</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="macgregor_2005.png"/>
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</mediaobject>
<caption>A schematic diagram of the different components and connections in the growth hormone secretory system.  Somatostatin (SOM) inhibits the secretion of both growth hormone-releasing hormone (GHRH) and growth hormone (GH).  After a delay, GH feeds back to prime the pool of releasable somatostatin, resulting in the bulk release of somatostatin, which in turn allows further GHRH release and and another burst of GH.</caption>
</informalfigure>
</sect1>
</article>
</documentation> 



  
  
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                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 220.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 227.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 1000.0 </cn>
            <apply>
              <and/>
              <apply>
                <geq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 228.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 229.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
            <apply>
              <and/>
              <apply>
                <geq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 230.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 310.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 1000.0 </cn>
            <apply>
              <and/>
              <apply>
                <geq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 311.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 312.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
            <apply>
              <and/>
              <apply>
                <geq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 313.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 321.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 1000.0 </cn>
            <apply>
              <and/>
              <apply>
                <geq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 322.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 323.0 </cn>
              </apply>
            </apply>
          </piece>
          <otherwise>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
          </otherwise>
        </piecewise>
      </apply>  
    </math> 
  </component>
  
  <component cmeta:id="s" name="s">
     
    <variable cmeta:id="s_s" initial_value="0.0" name="s" public_interface="out" units="nanomolar"/> 
    
    <variable initial_value="50.0" name="Is2" units="flux"/>
    
    <variable name="Is" public_interface="in" units="flux"/>
    <variable name="k7" public_interface="in" units="first_order_rate_constant"/>
    <variable name="g" public_interface="in" units="dimensionless"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> s </ci> 
        </apply>
        <apply>
          <plus/> 
          <apply>
            <minus/>
            <apply>
              <times/>
              <ci> Is </ci>
              <ci> g </ci>
            </apply>
            <apply>
              <times/>
              <ci> k7 </ci>
              <ci> s </ci>
            </apply>
          </apply>
          <ci> Is2 </ci>
        </apply>  
      </apply> 
    </math> 
  </component>

  <component cmeta:id="se" name="se">
     
    <variable initial_value="0.0" name="se" public_interface="out" units="nanomolar"/> 
    
    <variable initial_value="10.0" name="Ise" units="flux"/>
    
    <variable name="k7" public_interface="in" units="first_order_rate_constant"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> se </ci> 
        </apply>
        <apply>
          <minus/>
          <ci> Ise </ci>
          <apply>
            <times/>
            <ci> k7 </ci>
            <ci> se </ci>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>

  <component cmeta:id="f" name="f">
     
    <variable initial_value="0.3" name="f" public_interface="out" units="dimensionless"/> 
    
    <variable initial_value="0.1" name="k1" units="second_order_rate_constant"/>
    <variable initial_value="0.002" name="k2" units="first_order_rate_constant"/>
    <variable initial_value="0.018" name="k3" units="first_order_rate_constant"/>
    <variable name="phi_b_s" units="dimensionless"/>
    <variable initial_value="0.029" name="sb" units="dimensionless"/>
    <variable initial_value="0.3" name="delta_b" units="dimensionless"/>
    
    <variable name="r" public_interface="in" units="nanomolar"/>
    <variable name="c" public_interface="in" units="nanomolar"/>
    <variable name="s" public_interface="in" units="nanomolar"/>
    <variable name="se" public_interface="in" units="nanomolar"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> f </ci> 
        </apply>
        <apply>
          <plus/> 
          <apply>
            <minus/>
            <apply>
              <times/>
              <ci> k1 </ci>
              <apply>
                <plus/>
                <ci> r </ci>
                <ci> c </ci>
              </apply>
              <ci> f </ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <apply>
              <plus/>
              <ci> k2 </ci>
              <apply>
                <times/>
                <ci> k3 </ci>
                <ci> phi_b_s </ci>
              </apply>
            </apply>
            <apply>
              <minus/>
              <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn> 
              <ci> f </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    
      <apply id="phi_b_s_calculation">
        <eq/>
        <ci> phi_b_s </ci>
        <apply>
          <divide/>
          <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn> 
          <apply>
            <plus/>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/>
                  <apply>
                    <minus/>
                    <apply>
                      <log/>
	              <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_nanomolar"> 1.0 </cn>
                        <apply>
                          <plus/>
                          <ci> s </ci>
                          <ci> se </ci>
		        </apply>
                      </apply>
                    </apply>
                    <ci> sb </ci>
                  </apply>
                </apply>
                <ci> delta_b </ci>
              </apply>
            </apply>
          </apply>  
        </apply>
      </apply>
    </math> 
  </component>

  <component cmeta:id="h" name="h">
     
    <variable cmeta:id="h_h" initial_value="0.0" name="h" public_interface="out" units="nanomolar"/> 
    
    <variable initial_value="0.5" name="k4" units="first_order_rate_constant"/>
    <variable initial_value="71.0" name="k5" units="first_order_rate_constant"/>
    <variable name="phi_r_s" units="dimensionless"/>
    <variable initial_value="-0.56" name="sr" units="dimensionless"/>
    <variable initial_value="0.2" name="delta_r" units="dimensionless"/>
    
    <variable name="f" public_interface="in" units="dimensionless"/>
    <variable name="k8" public_interface="in" units="first_order_rate_constant"/>
    <variable name="j1" public_interface="in" units="dimensionless"/>
    <variable name="r" public_interface="in" units="nanomolar"/>
    <variable name="c" public_interface="in" units="nanomolar"/>
    <variable name="s" public_interface="in" units="nanomolar"/>
    <variable name="se" public_interface="in" units="nanomolar"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> h </ci> 
        </apply>
        <apply>
          <times/>
          <ci> j1 </ci> 
          <apply>
            <minus/>
            <apply>
              <times/>
              <apply>
                <plus/>
                <ci> k4 </ci>
                <apply>
                  <times/>
                  <ci> k5 </ci>
                  <apply>
                    <minus/>
                    <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn> 
                    <ci> phi_r_s </ci>
                  </apply>
                </apply>
              </apply>
              <apply>
                <times/>
                <apply>
                  <plus/>
                  <ci> r </ci>
                  <ci> c </ci>
                </apply>
                <ci> f </ci>
              </apply>
            </apply>
            <apply>
              <times/>
              <ci> k8 </ci> 
              <ci> h </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    
      <apply id="phi_r_s_calculation">
        <eq/>
        <ci> phi_r_s </ci>
        <apply>
          <divide/>
          <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn> 
          <apply>
            <plus/>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn>
            <apply>
              <exp/>
              <apply>
                <divide/>
                <apply>
                  <minus/>
                  <apply>
                    <minus/>
                    <apply>
                      <log/>
		      <apply>
                        <times/>
                        <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="per_nanomolar"> 1.0 </cn>
                        <apply>
                          <plus/>
                          <ci> s </ci>
                          <ci> se </ci>
		        </apply>
		      </apply>
                    </apply>
                    <ci> sr </ci>
                  </apply>
                </apply>
                <ci> delta_r </ci>
              </apply>
            </apply>
          </apply>  
        </apply>
      </apply>
    </math> 
  </component>

  <component cmeta:id="g" name="g">
     
    <variable cmeta:id="g_g" initial_value="2.0" name="g" public_interface="out" units="dimensionless"/> 
    
    <variable initial_value="1.0" name="g1" units="first_order_rate_constant"/>
    <variable initial_value="5.0" name="gmax" units="dimensionless"/>
    <variable initial_value="0.008" name="g2" units="per_nanomolar"/>
    <variable name="hact" units="dimensionless"/>
    <variable initial_value="2.0" name="n2" units="dimensionless"/>
    <variable initial_value="30.0" name="theta_2" units="dimensionless"/>
    
    <variable name="h_delta" public_interface="in" units="dimensionless"/>
    <variable name="Is" public_interface="in" units="flux"/>
    <variable name="j1" public_interface="in" units="dimensionless"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> g </ci> 
        </apply>
        <apply>
          <minus/> 
          <apply>
            <times/>
            <ci> g1 </ci>
            <ci> hact </ci>
            <apply>
              <divide/>
              <apply>
                <minus/> 
                <ci> gmax </ci>
                <ci> g </ci>
              </apply>
              <ci> gmax </ci>
            </apply>
          </apply>
          <apply>
            <times/>
            <ci> g2 </ci>
            <ci> Is </ci>
            <ci> g </ci> 
          </apply>
        </apply>  
      </apply>
 
      <apply id="hact_calculation">
        <eq/>
        <ci> hact </ci>
        <apply>
          <divide/>
          <apply>
            <power/>
            <ci> h_delta </ci>
            <ci> n2 </ci>
          </apply>
          <apply>
            <plus/>
            <apply>
              <power/>
              <ci> h_delta </ci>
              <ci> n2 </ci>
            </apply>
            <apply>
              <power/>
              <apply>
                <times/>
                <ci> j1 </ci>
                <ci> theta_2 </ci>
              </apply>
              <ci> n2 </ci>
            </apply>
          </apply>  
        </apply>
      </apply>
    </math> 
  </component>

  <component cmeta:id="hh" name="hh">
     
    <variable initial_value="0.0" name="hh" public_interface="out" units="nanomolar"/> 
    
    <variable initial_value="50.0" name="Ih" units="flux"/>
    
    <variable name="j1" public_interface="in" units="dimensionless"/>
    <variable name="k8" public_interface="in" units="first_order_rate_constant"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <apply>
          <diff/> 
          <bvar>
            <ci>time</ci>
          </bvar> 
          <ci> hh </ci> 
        </apply>
        <apply>
          <times/>
          <ci> j1 </ci> 
          <apply>
            <minus/>
            <ci> Ih </ci>
            <apply>
              <times/>
              <ci> k8 </ci>
              <ci> hh </ci>
            </apply>
          </apply>
        </apply>  
      </apply> 
    </math> 
  </component>
  
  <component name="model_parameters">
    <variable name="h_delta" public_interface="out" units="dimensionless"/>
    <variable name="h_delta1" public_interface="out" units="dimensionless"/>
    <variable initial_value="10" name="j1" public_interface="out" units="dimensionless"/>
    <variable initial_value="5.0" name="k7" public_interface="out" units="first_order_rate_constant"/>
    <variable name="Is" public_interface="out" units="flux"/>
    <variable initial_value="0.07" name="k8" public_interface="out" units="first_order_rate_constant"/>
    <variable initial_value="0.01" name="c" public_interface="out" units="nanomolar"/>

    <variable initial_value="60.0" name="delta" units="per_nanomolar"/>
    <variable initial_value="15.0" name="delta1" units="per_nanomolar"/>
    
    <variable name="h" public_interface="in" units="nanomolar"/>
    <variable name="hh" public_interface="in" units="nanomolar"/>
    <variable name="time" public_interface="in" units="minute"/> 
    
    <math xmlns="http://www.w3.org/1998/Math/MathML"> 
      <apply>
        <eq/> 
        <ci> h_delta </ci> 
        <apply>
          <times/>
          <apply>
            <plus/> 
            <ci> h </ci>
            <ci> hh </ci>
          </apply>
          <ci> delta </ci>
        </apply>
      </apply> 

      <apply>
        <eq/> 
        <ci> h_delta1 </ci> 
        <apply>
          <times/>
          <apply>
            <plus/> 
            <ci> h </ci>
            <ci> hh </ci>
          </apply>
          <ci> delta1 </ci>
        </apply>
      </apply>

      <apply>
        <eq/>
        <ci> Is </ci>
        <piecewise>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 10.0 </cn>
            <apply>
              <and/>
              <apply>
                <gt/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 0.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 90.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
            <apply>
              <and/>
              <apply>
                <gt/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 90.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 180.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 10.0 </cn>
            <apply>
              <and/>
              <apply>
                <gt/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 180.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 270.0 </cn>
              </apply>
            </apply>
          </piece>
          <piece>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
            <apply>
              <and/>
              <apply>
                <gt/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 270.0 </cn>
              </apply>
              <apply>
                <leq/>
                <ci> time </ci>
                <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="minute"> 360.0 </cn>
              </apply>
            </apply>
          </piece>
          <otherwise>
            <cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
          </otherwise>
        </piecewise>
      </apply> 
    </math> 
  </component>
  
  
  <connection>
    <map_components component_1="r" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="s" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="se" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="f" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>

  <connection>
    <map_components component_1="h" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="g" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="hh" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>

  <connection>
    <map_components component_1="model_parameters" component_2="environment"/>
    <map_variables variable_1="time" variable_2="time"/>
  </connection>
  
  <connection>
    <map_components component_1="r" component_2="s"/>
    <map_variables variable_1="s" variable_2="s"/>
  </connection>

  <connection>
    <map_components component_1="r" component_2="model_parameters"/>
    <map_variables variable_1="h_delta1" variable_2="h_delta1"/>
    <map_variables variable_1="j1" variable_2="j1"/>
  </connection>

  <connection>
    <map_components component_1="s" component_2="g"/>
    <map_variables variable_1="g" variable_2="g"/>
  </connection>

  <connection>
    <map_components component_1="s" component_2="model_parameters"/>
    <map_variables variable_1="Is" variable_2="Is"/>
    <map_variables variable_1="k7" variable_2="k7"/>
  </connection>

  <connection>
    <map_components component_1="se" component_2="model_parameters"/>
    <map_variables variable_1="k7" variable_2="k7"/>
  </connection>

  <connection>
    <map_components component_1="f" component_2="model_parameters"/>
    <map_variables variable_1="c" variable_2="c"/>
  </connection>

  <connection>
    <map_components component_1="f" component_2="r"/>
    <map_variables variable_1="r" variable_2="r"/>
  </connection>

  <connection>
    <map_components component_1="f" component_2="s"/>
    <map_variables variable_1="s" variable_2="s"/>
  </connection>

  <connection>
    <map_components component_1="h" component_2="model_parameters"/>
    <map_variables variable_1="c" variable_2="c"/>
    <map_variables variable_1="j1" variable_2="j1"/>
    <map_variables variable_1="k8" variable_2="k8"/>
    <map_variables variable_1="h" variable_2="h"/>
  </connection>

  <connection>
    <map_components component_1="h" component_2="r"/>
    <map_variables variable_1="r" variable_2="r"/>
  </connection>

  <connection>
    <map_components component_1="h" component_2="s"/>
    <map_variables variable_1="s" variable_2="s"/>
  </connection>

  <connection>
    <map_components component_1="h" component_2="se"/>
    <map_variables variable_1="se" variable_2="se"/>
  </connection>

  <connection>
    <map_components component_1="f" component_2="se"/>
    <map_variables variable_1="se" variable_2="se"/>
  </connection>
  
  <connection>
    <map_components component_1="h" component_2="f"/>
    <map_variables variable_1="f" variable_2="f"/>
  </connection>

  <connection>
    <map_components component_1="g" component_2="model_parameters"/>
    <map_variables variable_1="Is" variable_2="Is"/>
    <map_variables variable_1="j1" variable_2="j1"/>
    <map_variables variable_1="h_delta" variable_2="h_delta"/>
  </connection>

  <connection>
    <map_components component_1="hh" component_2="model_parameters"/>
    <map_variables variable_1="j1" variable_2="j1"/>
    <map_variables variable_1="k8" variable_2="k8"/>
    <map_variables variable_1="hh" variable_2="hh"/>
  </connection>
  
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    <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Modelling the hypothalamic control of growth hormone secretion: the full pituitary + hypothalamic model</dc:title>
	<dc:publisher xmlns:dc="http://purl.org/dc/elements/1.1/">The University of Auckland, Auckland Bioengineering Institute</dc:publisher>
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    <dcterms:alternative xmlns:dcterms="http://purl.org/dc/terms/">exogenous somatostatin</dcterms:alternative>
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    <rdf:value>I've checked the model in COR and have corrected all the units.  I've also added some piecewise equations to stimulate the model (as set out in the figure legends of the paper).</rdf:value>
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        MacGregor and Leng's 2005 mathematical model of hypothalamic control of growth hormone secretion.
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    <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Journal of Neuroendocrinology</dc:title>
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    <rdf:value>The model now runs in PCEnv to replicate the published results (as shown in figure 12).  The only difference is my stimulus was hand written by a piecewise equation where as the model authors used some sort of a random pulse generator...  I probably need to make the piecewise equation carry on for longer to get this result.</rdf:value>
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    <dc:title xmlns:dc="http://purl.org/dc/elements/1.1/">Modelling the hypothalamic control of growth hormone secretion.</dc:title>
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