- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2008-04-03 00:00:30+13:00
- Desc:
- committing version01 of guyton_atrial_natriuretic_peptide_2008
- Permanent Source URI:
- http://models.cellml.org/workspace/guyton_atrial_natriuretic_peptide_2008/rawfile/44c38ff1d55f28382340595baeaa68ce9120088d/guyton_atrial_natriuretic_peptide_2008.cellml
<?xml version='1.0' encoding='utf-8'?>
<model xmlns="http://www.cellml.org/cellml/1.0#" xmlns:cellml="http://www.cellml.org/cellml/1.0#" xmlns:cmeta="http://www.cellml.org/metadata/1.0#" xmlns:xlink="http://www.w3.org/1999/xlink" name="atrial_natriuretic_peptide_CellML1_0_model" cmeta:id="atrial_natriuretic_peptide_CellML1_0_model">
<!-- ========================================== DOCUMENTATION ============================================== -->
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Guyton Model: Atrial Natriuretic Peptide</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 CellML model has not been validated. The equations in this file may contain errors and the output from the model may not conform to the results from the MODSIM program. 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). Work is underway to fix these omissions and validate the CellML model. We also anticipate that many of these problems will be fixed when the CellML 1.0 models are combined in a CellML 1.1 format.
</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 the control of atrial natriuretic peptide secretion by the left and right atria of the heart. It also calculates a multiplier factor for controlling the resistance of the afferent arterioles (AAR) of the kidneys.
</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="atrial_natriuretic_peptide_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="anp.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>
<ulink url="http://arjournals.annualreviews.org/doi/abs/10.1146/annurev.ph.34.030172.000305">Circulation: Overall Regulation</ulink>, A.C. Guyton, T.G. Coleman, and H.J. Granger, 1972, <ulink url="http://www.biophysj.org/">
<emphasis>Annual Review of Physiology</emphasis>
</ulink>, 34, 13-44. (A <ulink url="http://arjournals.annualreviews.org/doi/pdf/10.1146/annurev.ph.34.030172.000305?cookieSet=1">PDF</ulink> version of the article are available to journal subscribers on the <emphasis>Annual Review of Physiology</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=4334846&query_hl=1&itool=pubmed_docsum">PubMed ID: 4334846</ulink>
</para>
</sect1>
</article>
</documentation>
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<!--
The following RDF block contains metadata that applies to this document
as a whole, as indicated by the empty about attribute on the
<rdf:Description> element.
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<rdf:Description rdf:about="">
<!--
The Model Builder Metadata. The Dublin Core "creator" element is used
to indicate the person who translated the model into CellML.
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<dc:creator rdf:parseType="Resource">
<vCard:N rdf:parseType="Resource">
<vCard:Family>Terkildsen</vCard:Family>
<vCard:Given>Jonna</vCard:Given>
</vCard:N>
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<rdf:value>j.terkildsen@auckland.ac.nz</rdf:value>
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<vCard:ORG rdf:parseType="Resource">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
</vCard:ORG>
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<!--
The Creation Date metadata. This is the date on which the model
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<dcterms:created rdf:parseType="Resource">
<dcterms:W3CDTF>2008-04-03</dcterms:W3CDTF>
</dcterms:created>
<!--
The Modification History metadata. This lists the changes that have been
made to the document, who made the changes, and when they were made.
-->
<!-- The Publisher metadata. -->
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
</rdf:Description>
</rdf:RDF>
<!-- =================================================================================================================== -->
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#atrial_natriuretic_peptide_CellML1_0_model">
<rdf:value>
This section calculates the control of atrial natriuretic peptide secretion by the
left and right atria of the heart. It also calculates a multiplier factor for
controlling the resistance of the afferent arterioles (AAR) of the kidneys.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- ===================================== ENVIRONMENT COMPONENT ============================================== -->
<component name="environment">
<variable name="time" units="second" private_interface="none" public_interface="out"/>
</component>
<!-- ======================================== ATRIAL NATRIURETIC PEPTIDE TOP-LEVEL COMPONENT ============================================= -->
<component name="atrial_natriuretic_peptide" cmeta:id="atrial_natriuretic_peptide">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#atrial_natriuretic_peptide">
<rdf:value>
Encapsulation grouping component containing all the components in the Atrial Natriuretic Peptide Model.
The inputs and outputs of the Atrial Natriuretic Peptide Model must be passed by this component.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<variable name="time" units="second" private_interface="out" public_interface="in"/>
<!-- Inputs from components in other models -->
<variable name="PLA" initial_value="2" units="dimensionless" private_interface="out" public_interface="none"/>
<variable name="PRA" initial_value="0.00852183" units="dimensionless" private_interface="out" public_interface="none"/>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="atrial_natriuretic_peptide" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- ======================================== TOTAL ATRIAL NATRIURETIC PEPTIDE SECRETED ============================================= -->
<component name="total_ANP_secreted" cmeta:id="total_ANP_secreted">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#total_ANP_secreted">
<rdf:value>
ANP1, ANP2, ANP3, ANP3A, and ANP4:
Calculation of the total amount of atrial natriuretic peptide secreted at
any given time. Block ANP1 determines the pressure level at which changes
in left atrial pressure (PLA) will begin to affect atrinatriuretic peptide
secretion. Block 1A sets a lower limit of zero for this secretion.
Block ANP2 calculates from the pressure level in the right atrium (PRA) the
stimulation of ANP output by the right atrium. Block 3 multiplies the
output of the right atrium by two-fold (against a one-fold amount secreted
by the left atrium). Block 3A sets a lower limit of zero for right atrial
output. Block 4 adds the outputs from the left atrium and right atrium.
ANP5:
Block 5 normalizes the ANP secretion under normal conditions to a value of 1.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="PLA" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="PRA" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANP" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Internal variables -->
<variable name="ANPL" units="dimensionless" private_interface="none" public_interface="none"/>
<variable name="ANPR2" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ANP1_and_ANP1A">
<eq/>
<ci>ANPL</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<apply>
<minus/>
<ci>PLA</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<minus/>
<ci>PLA</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
</otherwise>
</piecewise>
</apply>
<apply id="ANP2_ANP3_and_ANP3A">
<eq/>
<ci>ANPR2</ci>
<piecewise>
<piece>
<cn cellml:units="dimensionless">0</cn>
<apply>
<lt/>
<apply>
<times/>
<apply>
<plus/>
<ci>PRA</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<times/>
<apply>
<plus/>
<ci>PRA</ci>
<cn cellml:units="dimensionless">1</cn>
</apply>
<cn cellml:units="dimensionless">2</cn>
</apply>
</otherwise>
</piecewise>
</apply>
<apply id="ANP4_and_ANP5">
<eq/>
<ci>ANP</ci>
<apply>
<divide/>
<apply>
<plus/>
<ci>ANPL</ci>
<ci>ANPR2</ci>
</apply>
<cn cellml:units="dimensionless">3</cn>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="total_ANP_secreted" component_2="atrial_natriuretic_peptide"/>
<map_variables variable_1="PLA" variable_2="PLA"/>
<map_variables variable_1="PRA" variable_2="PRA"/>
</connection>
<!-- ======================================== ATRIAL NATRIURETIC PEPTIDE INTO CIRCULATION ============================================= -->
<component name="ANP_into_circulation" cmeta:id="ANP_into_circulation">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#ANP_into_circulation">
<rdf:value>
ANP 7:
This block allows infusion of ANP into the circulation (ANPINF). The output
of the block is ANP1 which is the total rate of ANP entering the circulation
at any given time.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANP" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANP1" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANPKNS" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="ANPINF" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ANP7">
<eq/>
<ci>ANP1</ci>
<piecewise>
<piece>
<ci>ANPKNS</ci>
<apply>
<gt/>
<ci>ANPKNS</ci>
<cn cellml:units="dimensionless">0</cn>
</apply>
</piece>
<otherwise>
<apply>
<plus/>
<ci>ANP</ci>
<ci>ANPINF</ci>
</apply>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="ANP_into_circulation" component_2="total_ANP_secreted"/>
<map_variables variable_1="ANP" variable_2="ANP"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="ANP_into_circulation" component_2="parameter_values"/>
<map_variables variable_1="ANPKNS" variable_2="ANPKNS"/>
<map_variables variable_1="ANPINF" variable_2="ANPINF"/>
</connection>
<!-- ======================================== ATRIAL NATRIURETIC PEPTIDE IN PLASMA ============================================= -->
<!-- ======================================== CHECK THIS EQUATION! REMOVED DAMPING FROM DE!!! ============================================= -->
<component name="ANP_in_plasma" cmeta:id="ANP_in_plasma">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#ANP_in_plasma">
<rdf:value>
ANP8, ANP9, and ANP10:
Calculation of the concentration of ANP in the plasma (ANPC) from the rate of
entry of ANP into the plasma (ANP1). The time constant for build-up of ANP in
the circulation is determined by ANPTC in Block 9. ANPC is normalized to 1.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANP1" units="dimensionless" private_interface="none" public_interface="in"/>
<variable name="time" units="second" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANPC" initial_value="1.0" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANPTC" units="dimensionless" private_interface="none" public_interface="in"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ANP8_to_ANP10">
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ANPC</ci>
</apply>
<apply>
<divide/>
<apply>
<minus/>
<ci>ANP1</ci>
<ci>ANPC</ci>
</apply>
<ci>ANPTC</ci>
</apply>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="ANP_in_plasma" component_2="ANP_into_circulation"/>
<map_variables variable_1="ANP1" variable_2="ANP1"/>
</connection>
<connection>
<map_components component_1="ANP_in_plasma" component_2="atrial_natriuretic_peptide"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="ANP_in_plasma" component_2="parameter_values"/>
<map_variables variable_1="ANPTC" variable_2="ANPTC"/>
</connection>
<!-- ======================================== ANP EFFECT ON RENAL AFFERENT ARTERIOLAR RESISTANCE ============================================= -->
<component name="ANP_effect_on_renal_afferent_arteriolar_resistance" cmeta:id="ANP_effect_on_renal_afferent_arteriolar_resistance">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="#ANP_effect_on_renal_afferent_arteriolar_resistance">
<rdf:value>
ANP11:
This curve calculates a multiplier factor (ANPX) for determining the effect
of ANP on the afferent arteriolar resistance of the kidneys. The upper limit
of ANPX is ANPXUL.
ANP 12:
This block sets the lower limit of ANPX equal to -1.
</rdf:value>
</rdf:Description>
</rdf:RDF>
<!-- Inputs from other components -->
<variable name="ANPC" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Outputs to other components -->
<variable name="ANPX" units="dimensionless" private_interface="none" public_interface="out"/>
<!-- Parameters from parameter_file -->
<variable name="ANPXUL" units="dimensionless" private_interface="none" public_interface="in"/>
<!-- Internal variables -->
<variable name="ANPX1" units="dimensionless" private_interface="none" public_interface="none"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply id="ANP11">
<eq/>
<ci>ANPX1</ci>
<apply>
<minus/>
<ci>ANPXUL</ci>
<apply>
<divide/>
<ci>ANPXUL</ci>
<apply>
<times/>
<cn cellml:units="dimensionless">0.5555556</cn>
<apply>
<plus/>
<cn cellml:units="dimensionless">1</cn>
<ci>ANPC</ci>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply id="ANP12">
<eq/>
<ci>ANPX</ci>
<piecewise>
<piece>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
<apply>
<lt/>
<ci>ANPX1</ci>
<apply>
<minus/>
<cn cellml:units="dimensionless">1</cn>
</apply>
</apply>
</piece>
<otherwise>
<ci>ANPX1</ci>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<!-- INPUT CONNECTIONS -->
<connection>
<map_components component_1="ANP_effect_on_renal_afferent_arteriolar_resistance" component_2="ANP_in_plasma"/>
<map_variables variable_1="ANPC" variable_2="ANPC"/>
</connection>
<!-- PARAMETER CONNECTIONS -->
<connection>
<map_components component_1="ANP_effect_on_renal_afferent_arteriolar_resistance" component_2="parameter_values"/>
<map_variables variable_1="ANPXUL" variable_2="ANPXUL"/>
</connection>
<component name="parameter_values" cmeta:id="parameter_values">
<variable name="ANPKNS" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- overriding value of ANP secretion rate -->
<variable name="ANPINF" units="dimensionless" initial_value="0" private_interface="none" public_interface="out"/> <!-- rate of exogenous ANP infusion -->
<variable name="ANPTC" units="dimensionless" initial_value="4" private_interface="none" public_interface="out"/> <!-- time constant, ANP accumulation and destruction [P] -->
<variable name="ANPXUL" units="dimensionless" initial_value="10" private_interface="none" public_interface="out"/> <!-- ANPX upper limit [P] -->
</component>
<!-- ============================================================ GROUPING =============================================================== -->
<group>
<relationship_ref relationship="containment"/>
<component_ref component="atrial_natriuretic_peptide">
<component_ref component="total_ANP_secreted"/>
<component_ref component="ANP_into_circulation"/>
<component_ref component="ANP_in_plasma"/>
<component_ref component="ANP_effect_on_renal_afferent_arteriolar_resistance"/>
</component_ref>
</group>
<group>
<relationship_ref relationship="encapsulation"/>
<component_ref component="atrial_natriuretic_peptide">
<component_ref component="parameter_values"/>
<component_ref component="total_ANP_secreted"/>
<component_ref component="ANP_into_circulation"/>
<component_ref component="ANP_in_plasma"/>
<component_ref component="ANP_effect_on_renal_afferent_arteriolar_resistance"/>
</component_ref>
</group>
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<rdf:Description rdf:about="#atrial_natriuretic_peptide_CellML1_0_model">
<rdf:value>
This section calculates the control of atrial natriuretic peptide secretion by the
left and right atria of the heart. It also calculates a multiplier factor for
controlling the resistance of the afferent arterioles (AAR) of the kidneys.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="">
<dc:publisher>
The University of Auckland, Bioengineering Institute
</dc:publisher>
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<rdf:Description rdf:about="#ANP_into_circulation">
<rdf:value>
ANP 7:
This block allows infusion of ANP into the circulation (ANPINF). The output
of the block is ANP1 which is the total rate of ANP entering the circulation
at any given time.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#ANP_in_plasma">
<rdf:value>
ANP8, ANP9, and ANP10:
Calculation of the concentration of ANP in the plasma (ANPC) from the rate of
entry of ANP into the plasma (ANP1). The time constant for build-up of ANP in
the circulation is determined by ANPTC in Block 9. ANPC is normalized to 1.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="rdf:#3e02e6d9-5d71-4910-846f-aef00c4b619a">
<vCard:Orgname>The University of Auckland</vCard:Orgname>
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<vCard:Given>Jonna</vCard:Given>
<vCard:Family>Terkildsen</vCard:Family>
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<dcterms:W3CDTF>2008-04-03</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="#ANP_effect_on_renal_afferent_arteriolar_resistance">
<rdf:value>
ANP11:
This curve calculates a multiplier factor (ANPX) for determining the effect
of ANP on the afferent arteriolar resistance of the kidneys. The upper limit
of ANPX is ANPXUL.
ANP 12:
This block sets the lower limit of ANPX equal to -1.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#total_ANP_secreted">
<rdf:value>
ANP1, ANP2, ANP3, ANP3A, and ANP4:
Calculation of the total amount of atrial natriuretic peptide secreted at
any given time. Block ANP1 determines the pressure level at which changes
in left atrial pressure (PLA) will begin to affect atrinatriuretic peptide
secretion. Block 1A sets a lower limit of zero for this secretion.
Block ANP2 calculates from the pressure level in the right atrium (PRA) the
stimulation of ANP output by the right atrium. Block 3 multiplies the
output of the right atrium by two-fold (against a one-fold amount secreted
by the left atrium). Block 3A sets a lower limit of zero for right atrial
output. Block 4 adds the outputs from the left atrium and right atrium.
ANP5:
Block 5 normalizes the ANP secretion under normal conditions to a value of 1.
</rdf:value>
</rdf:Description>
<rdf:Description rdf:about="#atrial_natriuretic_peptide">
<rdf:value>
Encapsulation grouping component containing all the components in the Atrial Natriuretic Peptide Model.
The inputs and outputs of the Atrial Natriuretic Peptide Model must be passed by this component.
</rdf:value>
</rdf:Description>
</rdf:RDF>
</model>