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<?xml version="1.0" encoding="utf-8"?>
<model 
	name="antidiuretic_hormone_parent_model"
	cmeta:id="antidiuretic_hormone_parent_model"
	
	xmlns="http://www.cellml.org/cellml/1.1#"
	xmlns:cellml="http://www.cellml.org/cellml/1.1#"
	xmlns:cmeta="http://www.cellml.org/metadata/1.0#"
	xmlns:xlink="http://www.w3.org/1999/xlink">

	<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
		<rdf:Description rdf:about="#antidiuretic_hormone_parent_model">
			<rdf:value>
			This is the CellML 1.1 "parent" file to test the Anti-diuretic Hormone Model. 
			</rdf:value>
		</rdf:Description>
	</rdf:RDF>

<!-- =====================================	DOCUMENTATION	============================================== -->
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
  <articleinfo>
  <title>Guyton Model: Antidiuretic Hormone</title>
  <author>
    <firstname>Catherine</firstname>
          <surname>Lloyd</surname>
    <affiliation>
      <shortaffil>Auckland Bioengineering Institute, University of Auckland</shortaffil>
    </affiliation>
  </author>
</articleinfo>

<section id="cellml_1_1">
<title>CellML 1.1 Version</title>
<para>
This is a CellML 1.1 version of the Antidiuretic Hormone Module of the Guyton Circulation model. To run, click on "Solve using OpenCell" and all 
dependent files and components will be imported. To run offline, please download all files from the <ulink url="/workspace/guyton_antidiuretic_hormone_2008/">workspace</ulink> into the same directory and open 
"antidiuretic_hormone_parent.cellml" in OpenCell.
</para>
</section>  

  <section id="sec_status">
    <title>Model Status</title>
    <para>
        This CellML model has been validated. Due to the differences between procedural code (in this case C-code) and 
		declarative languages (CellML), some aspects of the original model were not able to be encapsulated by the CellML 
		model (such as the damping of variables). This may effect the transient behaviour of the model, however the 
		steady-state behaviour would remain	the same. The equations in this file and the steady-state output from the 
		model conform to the results from the MODSIM program.
	</para>
  </section>
  <sect1 id="sec_structure">
  <title>Model Structure</title>

<para>
Arthur Guyton (1919-2003) was an American physiologist who became famous for his 1950s experiments in which he studied the 
physiology of cardiac output and its relationship with the peripheral circulation.  The results of these experiments 
challenged the conventional wisdom that it was the heart itself that controlled cardiac output.  Instead Guyton 
demonstrated that it was the need of the body tissues for oxygen which was the real regulator of cardiac output.  
The "Guyton Curves" describe the relationship between right atrial pressures and cardiac output, and they form a 
foundation for understanding the physiology of circulation. 
</para>

<para>
The Guyton model of fluid, electrolyte, and circulatory regulation is an extensive mathematical model of human circulatory 
physiology, capable of simulating a variety of experimental conditions, and contains a number of linked subsystems relating 
to circulation and its neuroendocrine control.
</para>

<para>
This is a CellML translation of the Guyton model of the regulation of the circulatory system.  The complete model consists of 
separate modules each of which characterise a separate physiological subsystems.  The Circulation Dynamics is the primary 
system, to which other modules/blocks are connected.  The other modules characterise the dynamics of the kidney, electrolytes 
and cell water, thirst and drinking, hormone regulation, autonomic regulation, cardiovascular system etc, and these feedback 
on the central circulation model.  The CellML code in these modules is based on the C code from the programme C-MODSIM 
created by Dr Jean-Pierre Montani.
</para>

<para>
This particular CellML model describes antidiuretic hormone and its control functions.  This section calculates the control 
of antidiuretic hormone secretion and also calculates multiplier factors for control of other aspects of circulatory 
function by antidiuretic hormone.  The major factors that are considered to affect the rate of antidiuretic hormone 
secretion are (1) a feedback effect of osmotic concentration in the extracellular fluids as determined from the concentration 
of sodium (CNA), and (2) a feedback effect of arterial pressure (PA).
</para>

<informalfigure float="0" id="full_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="full_model.png"/>
  </imageobject>
</mediaobject>
<caption>A systems analysis diagram for the full Guyton model describing circulation regulation.</caption>
</informalfigure>


<informalfigure float="0" id="antidiuretic_hormone_diagram">
<mediaobject>
  <imageobject>
    <objectinfo>
      <title>model diagram</title>
    </objectinfo>
    <imagedata fileref="antidiuretic_hormone.png"/>
  </imageobject>
</mediaobject>
<caption>A schematic diagram of the components and processes described in the current CellML model.</caption>
</informalfigure> 

<para>
There are several publications referring to the Guyton model. One of these papers is cited below:
</para>

<para>
Circulation: Overall Regulation,  A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972, 
            <emphasis>Annual Review of Physiology</emphasis>
          , 34, 13-44.  <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&amp;cmd=Retrieve&amp;dopt=AbstractPlus&amp;list_uids=4334846&amp;query_hl=1&amp;itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>

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

<!-- =======================================================    CITATION AND KEYWORD METADATA    ================================================== -->

	<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="#antidiuretic_hormone_parent_model">
			<bqs:reference rdf:parseType="Resource">
				<bqs:JournalArticle rdf:parseType="Resource">
					<dc:creator>
						<rdf:Seq>
							<rdf:li rdf:parseType="Resource">
								<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
								<vCard:N rdf:parseType="Resource">
									<vCard:Family>Guyton</vCard:Family>
									<vCard:Given></vCard:Given>
									<vCard:Other></vCard:Other>
								</vCard:N>
							</rdf:li>
							<rdf:li rdf:parseType="Resource">
								<rdf:type rdf:resource="http://www.cellml.org/bqs/1.0#Person" />
								<vCard:N rdf:parseType="Resource">
									<vCard:Family>Antidiuretic Hormone</vCard:Family>
									<vCard:Given></vCard:Given>
									<vCard:Other></vCard:Other>
								</vCard:N>
							</rdf:li>

						</rdf:Seq>
					</dc:creator>
					<dc:title>Description of Guyton antidiuretic hormone module</dc:title>
					<bqs:volume />
					<bqs:first_page />
					<bqs:last_page />
					<bqs:Journal rdf:parseType="Resource">
						<dc:title></dc:title>
					</bqs:Journal>
					<dcterms:issued rdf:parseType="Resource">
						<dcterms:W3CDTF>2008-00-00 00:00</dcterms:W3CDTF>
					</dcterms:issued>
				</bqs:JournalArticle>
			</bqs:reference>
			<bqs:reference rdf:parseType="Resource">
				<dc:subject rdf:parseType="Resource">
					<bqs:subject_type>keyword</bqs:subject_type>
					<rdf:value>
					<rdf:Bag>
						<rdf:li>physiology</rdf:li>
						<rdf:li>organ systems</rdf:li>
						<rdf:li>cardiovascular circulation</rdf:li>
						<rdf:li>antidiuretic hormone</rdf:li>
						<rdf:li>Guyton</rdf:li>
					</rdf:Bag>
					</rdf:value>
				</dc:subject>
			</bqs:reference>
		</rdf:Description>
	</rdf:RDF>

 
<!-- =============================================	Import the required units from the Units file	==================================================== -->
	<import xlink:href="units.cellml">
		<units name="minute" units_ref="minute"/>
		<units name="per_minute" units_ref="per_minute"/>
		<units name="beats_per_minute" units_ref="beats_per_minute"/>
		<units name="beats_per_minute_per_mmHg" units_ref="beats_per_minute_per_mmHg"/>
		<units name="minute_per_L" units_ref="minute_per_L"/>
		<units name="mmHg" units_ref="mmHg"/>
		<units name="per_mmHg" units_ref="per_mmHg"/>
		<units name="mmHg_per_mL" units_ref="mmHg_per_mL"/>
		<units name="mmHg_L" units_ref="mmHg_L"/>
		<units name="per_mmHg2" units_ref="per_mmHg2"/>
		<units name="mmHg3" units_ref="mmHg3"/>
		<units name="monovalent_mEq" units_ref="monovalent_mEq"/>
		<units name="monovalent_mEq_per_minute" units_ref="monovalent_mEq_per_minute"/>
		<units name="monovalent_mEq_per_litre" units_ref="monovalent_mEq_per_litre"/>
		<units name="mOsm" units_ref="mOsm"/>
		<units name="mOsm_per_litre" units_ref="mOsm_per_litre"/>
		<units name="mOsm_per_minute" units_ref="mOsm_per_minute"/>
		<units name="monovalent_mEq_per_litre_per_minute" units_ref="monovalent_mEq_per_litre_per_minute"/>
		<units name="litre2_per_monovalent_mEq_per_minute" units_ref="litre2_per_monovalent_mEq_per_minute"/>
		<units name="L_per_minute" units_ref="L_per_minute"/>
		<units name="per_mmHg_per_minute" units_ref="per_mmHg_per_minute"/>
		<units name="mL" units_ref="mL"/>
		<units name="gram_per_L" units_ref="gram_per_L"/>
		<units name="L_mmHg_per_gram" units_ref="L_mmHg_per_gram"/>
		<units name="L2_mmHg_per_gram2" units_ref="L2_mmHg_per_gram2"/>
		<units name="mmHg_minute_per_L" units_ref="mmHg_minute_per_L"/>
		<units name="mmHg_L_per_minute" units_ref="mmHg_L_per_minute"/>
		<units name="gram_per_minute" units_ref="gram_per_minute"/>
		<units name="mL_per_L" units_ref="mL_per_L"/>
		<units name="mL_per_L_per_mmHg" units_ref="mL_per_L_per_mmHg"/>
		<units name="mL_per_L_per_minute" units_ref="mL_per_L_per_minute"/>
		<units name="mL_per_minute_per_mmHg" units_ref="mL_per_minute_per_mmHg"/>
		<units name="L_mL_per_minute_per_mmHg" units_ref="L_mL_per_minute_per_mmHg"/>
		<units name="L_per_mL" units_ref="L_per_mL"/>
		<units name="L_per_mmHg" units_ref="L_per_mmHg"/>
		<units name="mL_per_minute" units_ref="mL_per_minute"/>
		<units name="L_per_minute_per_mmHg" units_ref="L_per_minute_per_mmHg"/>
		<units name="L_per_minute_per_mmHg2" units_ref="L_per_minute_per_mmHg2"/>
	</import>

<!-- =====================================	Import all Parameters and State Variables from the Parameter file	============================================== -->
	<import xlink:href="parameters.cellml">
		<component component_ref="parameter_values" name="parameter_values"/>
		<component component_ref="state_variables" name="state_variables"/>
	</import>

<!-- ============================================	Import Environment Component from the Environment file	============================================== -->
	<import xlink:href="environment.cellml">
		<component component_ref="environment" name="environment"/>
	</import>

<!-- ============================================	Import all the separate model files and their components	============================================== -->
	<import xlink:href="antidiuretic_hormone.cellml">
		<component component_ref="antidiuretic_hormone" name="antidiuretic_hormone"/>
	</import>

	
<!-- ========================================	INPUT VALUES		============================================= -->
	<component 	name="input_values" 
				cmeta:id="input_values">
		<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
			<rdf:Description rdf:about="#input_values">
				<rdf:value>
				Component to set all input values to 1.0 or a prescribed value.
				</rdf:value>
			</rdf:Description>
		</rdf:RDF>
		
		<variable name="CNA" 	initial_value="142.035"		units="monovalent_mEq_per_litre" private_interface="none" public_interface="out"/>
		<variable name="PA1" 	initial_value="103.525"		units="mmHg" private_interface="none" public_interface="out"/>
	</component>
	
<!-- ANTI-DIURETIC HORMONE INPUT CONNECTIONS -->
	<connection>
		<map_components component_1="antidiuretic_hormone" component_2="input_values"/>
		<map_variables variable_1="CNA" variable_2="CNA"/>
		<map_variables variable_1="PA1" variable_2="PA1"/>
	</connection>
	<connection>
		<map_components component_1="antidiuretic_hormone" component_2="environment"/>
		<map_variables variable_1="time" variable_2="time"/>
	</connection>


</model>