Location: Schenzle 1994 @ 6d869667a7cf / schenzle_1994.cellml

Author:
Catherine Lloyd <c.lloyd@auckland.ac.nz>
Date:
2010-04-06 12:41:16+12:00
Desc:
Added files to the workspace. Used this mdoel to try to curate Stilianakis et al. 1997 - but neither model runs to match the published results.
Permanent Source URI:
https://models.physiomeproject.org/workspace/schenzle_1994/rawfile/6d869667a7cfcd01cccc6a84abc2e44f7e8accc4/schenzle_1994.cellml

<?xml version='1.0' encoding='utf-8'?>

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<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>A model for AIDS pathogenesis</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 CellML model runs in OpenCell and COR but does not recreate the published results (figure 3). The units have been checked and they are consistent. The equations appear to match those in the paper (7a-7e) and the parameter values have been taken from section 7 of the paper (page 2075). The CellML model simulation output fails to oscillate.
          </para>
  </section>
  <sect1 id="sec_structure">
<title>Model Structure</title>

<para>
ABSTRACT: The idea is put forward and analysed numerically, that within an infected person HIV evolves to increase its reproductivity within the population of CD4+ cells. A mathematical model predicts initial viremia and CD4+ cell drop after HIV infection and thereafter a slow progressive decline in the number of CD4+ cells, although for an extended period HIV is kept at a relatively low level by an active immune response. The time span T until the number of CD4+ cells falls below 20 per cent of its normal value depends on several model parameters. Assuming Gaussian distributions for these parameters, the model predicts a distribution function for T which resembles the observed distribution function for the incubation period to AIDS.
</para>

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

<para>
A model for AIDS pathogenesis, Schenzle D, 1994,
            <emphasis>Statistics in Medicine</emphasis>, 13, (19-20), 2067-2079. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/7846411">PubMed ID: 7846411</ulink>
</para>

<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>reaction diagram</title>
    </objectinfo>
    <imagedata fileref="schenzle_1994.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram showing how susceptible T cells are infected by free HIV particles at a rate K to become infected T cells.  This process is influenced by the anti-HIV activity of the immune system against infected T cells and HIV. Note: X: The number of susceptible (non-infected) CD4+ T cells, Y: The number of HIV-infected CD4+ T cells, V: The number of free HIV particles, Z: The anti-HIV activity of the immune system towards removing infected CD4+ T cells and HIV, and K: The rate at which HIV infects susceptible CD4+ T cells.</caption>
</informalfigure>

</sect1>
</article>
</documentation>
  
  
  
  <units name="day">
    <unit units="second" multiplier="86400"/>
  </units>
  
  <units name="first_order_rate_constant">  
    <unit units="day" exponent="-1"/>
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    <variable units="first_order_rate_constant" name="mu0" initial_value="0.004"/>
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    <variable units="day" public_interface="in" name="time"/>
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        <ci> s </ci>
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		  <cn type="e-notation" cellml:units="dimensionless">1.0<sep/>11</cn>
		</apply>
      </apply>
    </math>
  </component>
  
  <component cmeta:id="Y" name="Y">
      
    <variable units="dimensionless" public_interface="out" name="Y" initial_value="100.0"/>
    
    <variable units="first_order_rate_constant" name="mu1" initial_value="0.30"/>
    <variable units="first_order_rate_constant" name="delta1" initial_value="0.30"/>
    
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  <component cmeta:id="CD4" name="CD4">
    <rdf:Description rdf:about="#CD4">
      <dcterms:alternative>total number of CD4+ T cells (susceptible and infected)</dcterms:alternative>
      <dc:title>CD4</dc:title>
    </rdf:Description> 
    <variable units="dimensionless" name="CD4"/>
    
    <variable units="dimensionless" public_interface="in" name="X"/>
	<variable units="dimensionless" public_interface="in" name="Y"/>
    
    <math xmlns="http://www.w3.org/1998/Math/MathML">
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        <ci> CD4 </ci>
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            <ci> X </ci>
            <ci> Y </ci>
          </apply>
		  <cn type="e-notation" cellml:units="dimensionless">1.0<sep/>11</cn>
        </apply>
      </apply>
    </math>
  </component>
  
  <component cmeta:id="V" name="V">
      
    <variable units="dimensionless" public_interface="out" name="V" initial_value="1000.0"/>
    
    <variable units="first_order_rate_constant" name="mu2" initial_value="1.0"/>
    <variable units="first_order_rate_constant" name="phi" initial_value="1000.0"/>
    <variable units="first_order_rate_constant" name="delta2" initial_value="1.0"/>
    
    <variable units="day" public_interface="in" name="time"/>
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  <component cmeta:id="Z" name="Z">
      
    <variable units="dimensionless" public_interface="out" name="Z" initial_value="0.0"/>
    
    <variable units="first_order_rate_constant" name="alpha" initial_value="1.0E-6"/>
    <variable units="first_order_rate_constant" name="beta" initial_value="0.5"/>
	<variable units="first_order_rate_constant" name="gamma" initial_value="0.5"/>
    <variable units="dimensionless" name="f_X"/>
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    <variable units="dimensionless" name="b" initial_value="0.2"/>
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    <variable units="day" public_interface="in" name="time"/>
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    <math xmlns="http://www.w3.org/1998/Math/MathML">
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		  <apply>
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              <power/>
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			  <cn cellml:units="dimensionless"> 2 </cn>
            </apply>
          </apply>
        </apply>
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      <apply id="f_X_eq">
        <eq/>
        <ci> f_X </ci>
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            <cn cellml:units="dimensionless"> 2.0 </cn>
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    </math>
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  <component cmeta:id="K" name="K">
      
    <variable units="first_order_rate_constant" public_interface="out" name="K" initial_value="1.35E-14"/>
    
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    <variable units="day" public_interface="in" name="time"/>
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    <math xmlns="http://www.w3.org/1998/Math/MathML">
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      </apply>
	  
	  <apply id="Kmax_eq">
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        <ci> Kmax </ci>
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          <times/>
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		  <cn cellml:units="dimensionless"> 20.0 </cn>
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      </apply>
    </math>
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    <map_variables variable_2="Z" variable_1="Z"/>
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    <map_components component_2="Z" component_1="V"/>
    <map_variables variable_2="Z" variable_1="Z"/>
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    <map_components component_2="X" component_1="Z"/>
    <map_variables variable_2="X" variable_1="X"/>
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    <map_components component_2="V" component_1="K"/>
    <map_variables variable_2="V" variable_1="V"/>
  </connection>
  
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    <map_variables variable_2="X" variable_1="X"/>
  </connection>
  
  <connection>
    <map_components component_2="Y" component_1="CD4"/>
    <map_variables variable_2="Y" variable_1="Y"/>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#" xmlns:bqs="http://www.cellml.org/bqs/1.0#" xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:dcterms="http://purl.org/dc/terms/" xmlns:vCard="http://www.w3.org/2001/vcard-rdf/3.0#">

  <rdf:Description rdf:about="#Z">
    <dcterms:alternative>anti-HIV activity</dcterms:alternative>
    <dc:title>Z</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#X">
    <dcterms:alternative>susceptible CD4+ T cells</dcterms:alternative>
    <dc:title>X</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#Y">
    <dcterms:alternative>infected CD4+ T cells</dcterms:alternative>
    <dc:title>Y</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#K">
    <dcterms:alternative>CD4+ T cell infection rate</dcterms:alternative>
    <dc:title>K</dc:title>
  </rdf:Description>
  <rdf:Description rdf:about="#V">
    <dcterms:alternative>free HIV particles</dcterms:alternative>
    <dc:title>V</dc:title>
  </rdf:Description>
  
  <rdf:Description rdf:about="">
      <dc:creator rdf:parseType="Resource">
        <vCard:N rdf:parseType="Resource">
          <vCard:Family>Lloyd</vCard:Family>
          <vCard:Given>Catherine</vCard:Given>
		  <vCard:Given>May</vCard:Given>
		</vCard:N>
        <vCard:EMAIL rdf:parseType="Resource">
          <rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
          <rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
        </vCard:EMAIL>
        <vCard:ORG rdf:parseType="Resource">
          <vCard:Orgname>The University of Auckland</vCard:Orgname>
          <vCard:Orgunit>Auckland Bioengineering Institute</vCard:Orgunit>
        </vCard:ORG>
      </dc:creator>
  
      <dcterms:created rdf:parseType="Resource">
        <dcterms:W3CDTF>2010-04-06</dcterms:W3CDTF>
      </dcterms:created>
    </rdf:Description>
    
    <rdf:Description rdf:about="#schenzle_1994">
      <cmeta:bio_entity>T lymphocyte</cmeta:bio_entity>
	  
      <bqs:reference rdf:parseType="Resource">
        <dc:subject rdf:parseType="Resource">
          <bqs:subject_type>keyword</bqs:subject_type>
          <rdf:value>
            <rdf:Bag>
              <rdf:li>viral dynamics</rdf:li>
              <rdf:li>HIV-1</rdf:li>
			  <rdf:li>T cell</rdf:li>
			  <rdf:li>CD4</rdf:li>
			  <rdf:li>lymphocyte</rdf:li>
              <rdf:li>immunology</rdf:li>
              <rdf:li>AIDS</rdf:li>
            </rdf:Bag>
          </rdf:value>
        </dc:subject>
      </bqs:reference>

      <bqs:reference rdf:parseType="Resource">
        <bqs:Pubmed_id>7846411</bqs:Pubmed_id>
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          <dc:creator>
            <rdf:Seq>
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                <bqs:Person rdf:parseType="Resource">
                  <vCard:N rdf:parseType="Resource">
                    <vCard:Family>Schenzle</vCard:Family>
                    <vCard:Given>D</vCard:Given>
				  </vCard:N>
                </bqs:Person>
              </rdf:li>
			</rdf:Seq>
          </dc:creator>
          <dc:title>
            A model for AIDS pathogenesis
          </dc:title>
          <dcterms:issued rdf:parseType="Resource">
            <dcterms:W3CDTF>1994-10</dcterms:W3CDTF>
          </dcterms:issued>
          <bqs:Journal rdf:parseType="Resource">
            <dc:title>Statistics in Medicine</dc:title>
          </bqs:Journal>
		  <bqs:volume>13</bqs:volume>
          <bqs:first_page>2067</bqs:first_page>
          <bqs:last_page>2079</bqs:last_page>
        </bqs:JournalArticle>
      </bqs:reference>
    </rdf:Description>
  </rdf:RDF>
</model>