- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2009-05-25 01:19:15+12:00
- Desc:
- committing version01 of chang_fujita_1999
- Permanent Source URI:
- https://models.physiomeproject.org/workspace/chang_fujita_1999/rawfile/838afae06bf9e4df5e957e1d1eb64e9c394e53b9/chang_fujita_1999_a.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : chang_model_1999.xml
CREATED : 20th January 2003
LAST MODIFIED : 9th April 2003
AUTHOR : Catherine Lloyd
The Bioengineering Institute
The University of Auckland
MODEL STATUS : This model conforms to the CellML 1.0 Specification released on
10th August 2001, and the 16/01/2002 CellML Metadata 1.0 Specification.
DESCRIPTION : This file contains a CellML description of Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.
CHANGES:
09/04/2003 - AAC - Added publication date information.
--><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#" cmeta:id="chang_fujita_1999_version01" name="chang_fujita_1999_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A Kinetic Model of the Thiazide-Sensitive Na-Cl Cotransporter</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 is the original unchecked version of the model imported from the previous
CellML model repository, 24-Jan-2006.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: The aim of this study was to construct a numerical model of the thiazide-sensitive Na-Cl cotransporter (TSC) that can predict kinetics of thiazide binding and substrate transport of TSC. We hypothesized that the mechanisms underlying these kinetic properties can be approximated by a state diagram in which the transporter has two binding sites, one for sodium and another for chloride and thiazide. On the basis of the state diagram, a system of linear equations that should be satisfied in the steady state was postulated. Numerical solution of these equations yielded model prediction of kinetics of thiazide binding and substrate transport. Rate constants, which determine transitional rates between states, were systematically adjusted to minimize a penalty function that was devised to quantitatively estimate the difference between model predictions and experimental results. With the resultant rate constants, the model could simulate the following experimental results: 1) dissociation constant of thiazide in the absence of sodium and chloride; 2) inhibitory effect of chloride on thiazide binding; 3) stimulatory effect of sodium on thiazide binding; 4) combined effects of sodium and chloride on thiazide binding; 5) dependence of sodium influx on extracellular sodium and chloride; and 6) inhibition of sodium influx by extracellular thiazide. We conclude that known kinetic properties of TSC can be predicted by a model which is based on a state diagram.
</para>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://ajprenal.physiology.org/cgi/content/abstract/276/6/F952">A kinetic model of the thiazide-sensitive Na-Cl cotransporter</ulink>, Hangil Chang and Toshiro Fujita, 1999, <ulink url="http://ajprenal.physiology.org/">
<emphasis>American Journal of Physiology</emphasis>
</ulink>, 276, F952-F959. (<ulink url="http://ajprenal.physiology.org/cgi/reprint/276/6/F952.pdf">PDF</ulink> and <ulink url="http://ajprenal.physiology.org/cgi/content/full/276/6/F952">full text</ulink> versions of the article are available to subscribers on the journal website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10362783&dopt=Abstract">PubMed ID: 10362783</ulink>
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>diagram of the model</title>
</objectinfo>
<imagedata fileref="chang_1999.png"/>
</imageobject>
</mediaobject>
<caption>State diagram for the thiazide-sensitive Na-Cl cotransporter (TSC). Transporter (E) has binding sites for sodium (Na ) and chloride (Cl). Thiazide diuretics (D) compete with chloride for the same binding site. <emphasis>_i</emphasis> is used to indicate which symbols belong to the intracellular side.</caption>
</informalfigure>
</sect1>
</article>
</documentation>
<!--
Below, we define some additional units for association with variables and
constants within the model.
-->
<units name="millimolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="flux">
<unit units="millimolar"/>
<unit units="second" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="millimolar" exponent="-1"/>
<unit units="second" exponent="-1"/>
</units>
<!--
The "environment" component is used to declare variables that are used by
all or most of the other components, in this case just "time".
-->
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
<!--
The following components describe all the transporters, reactants and
products involved in the reactions.
-->
<component cmeta:id="E" name="E">
<variable units="millimolar" public_interface="out" name="E"/>
<variable units="flux" public_interface="in" name="delta_E_rxn1"/>
<variable units="flux" public_interface="in" name="delta_E_rxn2"/>
<variable units="flux" public_interface="in" name="delta_E_rxn12"/>
<variable units="flux" public_interface="in" name="delta_E_rxn9"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>E</ci>
</apply>
<apply>
<plus/>
<ci>delta_E_rxn1</ci>
<ci>delta_E_rxn2</ci>
<ci>delta_E_rxn12</ci>
<ci>delta_E_rxn9</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="E_i" name="E_i">
<variable units="millimolar" public_interface="out" name="E_i"/>
<variable units="flux" public_interface="in" name="delta_E_i_rxn5"/>
<variable units="flux" public_interface="in" name="delta_E_i_rxn6"/>
<variable units="flux" public_interface="in" name="delta_E_i_rxn9"/>
<variable units="flux" public_interface="in" name="delta_E_i_rxn15"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>E_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_E_i_rxn5</ci>
<ci>delta_E_i_rxn6</ci>
<ci>delta_E_i_rxn9</ci>
<ci>delta_E_i_rxn15</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ED" name="ED">
<variable units="millimolar" public_interface="out" name="ED"/>
<variable units="flux" public_interface="in" name="delta_ED_rxn11"/>
<variable units="flux" public_interface="in" name="delta_ED_rxn12"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ED</ci>
</apply>
<apply>
<plus/>
<ci>delta_ED_rxn11</ci>
<ci>delta_ED_rxn12</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ED_i" name="ED_i">
<variable units="millimolar" public_interface="out" name="ED_i"/>
<variable units="flux" public_interface="in" name="delta_ED_i_rxn14"/>
<variable units="flux" public_interface="in" name="delta_ED_i_rxn15"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ED_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_ED_i_rxn14</ci>
<ci>delta_ED_i_rxn15</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENaD" name="ENaD">
<variable units="millimolar" public_interface="out" name="ENaD"/>
<variable units="flux" public_interface="in" name="delta_ENaD_rxn11"/>
<variable units="flux" public_interface="in" name="delta_ENaD_rxn13"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENaD</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENaD_rxn11</ci>
<ci>delta_ENaD_rxn13</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENaD_i" name="ENaD_i">
<variable units="millimolar" public_interface="out" name="ENaD_i"/>
<variable units="flux" public_interface="in" name="delta_ENaD_i_rxn14"/>
<variable units="flux" public_interface="in" name="delta_ENaD_i_rxn16"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENaD_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENaD_i_rxn14</ci>
<ci>delta_ENaD_i_rxn16</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENa" name="ENa">
<variable units="millimolar" public_interface="out" name="ENa"/>
<variable units="flux" public_interface="in" name="delta_ENa_rxn1"/>
<variable units="flux" public_interface="in" name="delta_ENa_rxn3"/>
<variable units="flux" public_interface="in" name="delta_ENa_rxn13"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENa</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENa_rxn1</ci>
<ci>delta_ENa_rxn3</ci>
<ci>delta_ENa_rxn13</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENa_i" name="ENa_i">
<variable units="millimolar" public_interface="out" name="ENa_i"/>
<variable units="flux" public_interface="in" name="delta_ENa_i_rxn5"/>
<variable units="flux" public_interface="in" name="delta_ENa_i_rxn7"/>
<variable units="flux" public_interface="in" name="delta_ENa_i_rxn16"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENa_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENa_i_rxn5</ci>
<ci>delta_ENa_i_rxn7</ci>
<ci>delta_ENa_i_rxn16</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ECl" name="ECl">
<variable units="millimolar" public_interface="out" name="ECl"/>
<variable units="flux" public_interface="in" name="delta_ECl_rxn2"/>
<variable units="flux" public_interface="in" name="delta_ECl_rxn4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ECl</ci>
</apply>
<apply>
<plus/>
<ci>delta_ECl_rxn2</ci>
<ci>delta_ECl_rxn4</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ECl_i" name="ECl_i">
<variable units="millimolar" public_interface="out" name="ECl_i"/>
<variable units="flux" public_interface="in" name="delta_ECl_i_rxn6"/>
<variable units="flux" public_interface="in" name="delta_ECl_i_rxn8"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ECl_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_ECl_i_rxn6</ci>
<ci>delta_ECl_i_rxn8</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENaCl" name="ENaCl">
<variable units="millimolar" public_interface="out" name="ENaCl"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_rxn3"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_rxn4"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_rxn10"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENaCl</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENaCl_rxn3</ci>
<ci>delta_ENaCl_rxn4</ci>
<ci>delta_ENaCl_rxn10</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="ENaCl_i" name="ENaCl_i">
<variable units="millimolar" public_interface="out" name="ENaCl_i"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_i_rxn7"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_i_rxn8"/>
<variable units="flux" public_interface="in" name="delta_ENaCl_i_rxn10"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>ENaCl_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_ENaCl_i_rxn7</ci>
<ci>delta_ENaCl_i_rxn8</ci>
<ci>delta_ENaCl_i_rxn10</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Na" name="Na">
<variable units="millimolar" public_interface="out" name="Na"/>
<variable units="flux" public_interface="in" name="delta_Na_rxn1"/>
<variable units="flux" public_interface="in" name="delta_Na_rxn4"/>
<variable units="flux" public_interface="in" name="delta_Na_rxn11"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na</ci>
</apply>
<apply>
<plus/>
<ci>delta_Na_rxn1</ci>
<ci>delta_Na_rxn4</ci>
<ci>delta_Na_rxn11</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Na_i" name="Na_i">
<variable units="millimolar" public_interface="out" name="Na_i"/>
<variable units="flux" public_interface="in" name="delta_Na_i_rxn8"/>
<variable units="flux" public_interface="in" name="delta_Na_i_rxn14"/>
<variable units="flux" public_interface="in" name="delta_Na_i_rxn5"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Na_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_Na_i_rxn5</ci>
<ci>delta_Na_i_rxn8</ci>
<ci>delta_Na_i_rxn14</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Cl" name="Cl">
<variable units="millimolar" public_interface="out" name="Cl"/>
<variable units="flux" public_interface="in" name="delta_Cl_rxn2"/>
<variable units="flux" public_interface="in" name="delta_Cl_rxn3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cl</ci>
</apply>
<apply>
<plus/>
<ci>delta_Cl_rxn2</ci>
<ci>delta_Cl_rxn3</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Cl_i" name="Cl_i">
<variable units="millimolar" public_interface="out" name="Cl_i"/>
<variable units="flux" public_interface="in" name="delta_Cl_i_rxn6"/>
<variable units="flux" public_interface="in" name="delta_Cl_i_rxn7"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>Cl_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_Cl_i_rxn6</ci>
<ci>delta_Cl_i_rxn7</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="D" name="D">
<variable units="millimolar" public_interface="out" name="D"/>
<variable units="flux" public_interface="in" name="delta_D_rxn12"/>
<variable units="flux" public_interface="in" name="delta_D_rxn13"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>D</ci>
</apply>
<apply>
<plus/>
<ci>delta_D_rxn12</ci>
<ci>delta_D_rxn13</ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="D_i" name="D_i">
<variable units="millimolar" public_interface="out" name="D_i"/>
<variable units="flux" public_interface="in" name="delta_D_i_rxn16"/>
<variable units="flux" public_interface="in" name="delta_D_i_rxn15"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci>D_i</ci>
</apply>
<apply>
<plus/>
<ci>delta_D_i_rxn16</ci>
<ci>delta_D_i_rxn15</ci>
</apply>
</apply>
</math>
</component>
<!--
The following components describe the reactions of the model.
-->
<component name="reaction1">
<variable units="millimolar" public_interface="in" name="E"/>
<variable units="millimolar" public_interface="in" name="Na"/>
<variable units="millimolar" public_interface="in" name="ENa"/>
<variable units="second_order_rate_constant" name="k1" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k1_" initial_value="4.183E5"/>
<variable units="flux" public_interface="out" name="delta_E_rxn1"/>
<variable units="flux" public_interface="out" name="delta_Na_rxn1"/>
<variable units="flux" public_interface="out" name="delta_ENa_rxn1"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="Na">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_rxn1" role="reactant"/>
</variable_ref>
<variable_ref variable="ENa">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_rxn1" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k1</ci>
<ci>E</ci>
<ci>Na</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k1_</ci>
<ci>ENa</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction2">
<variable units="millimolar" public_interface="in" name="E"/>
<variable units="millimolar" public_interface="in" name="Cl"/>
<variable units="millimolar" public_interface="in" name="ECl"/>
<variable units="second_order_rate_constant" name="k2" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k2_" initial_value="4.928E6"/>
<variable units="flux" public_interface="out" name="delta_E_rxn2"/>
<variable units="flux" public_interface="out" name="delta_Cl_rxn2"/>
<variable units="flux" public_interface="out" name="delta_ECl_rxn2"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="Cl">
<role stoichiometry="1" direction="forward" delta_variable="delta_Cl_rxn2" role="reactant"/>
</variable_ref>
<variable_ref variable="ECl">
<role stoichiometry="1" direction="forward" delta_variable="delta_ECl_rxn2" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k2</ci>
<ci>E</ci>
<ci>Cl</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k2_</ci>
<ci>ECl</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction3">
<variable units="millimolar" public_interface="in" name="ENa"/>
<variable units="millimolar" public_interface="in" name="Cl"/>
<variable units="millimolar" public_interface="in" name="ENaCl"/>
<variable units="second_order_rate_constant" name="k3" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k3_" initial_value="1.065E6"/>
<variable units="flux" public_interface="out" name="delta_ENa_rxn3"/>
<variable units="flux" public_interface="out" name="delta_Cl_rxn3"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_rxn3"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ENa">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="Cl">
<role stoichiometry="1" direction="forward" delta_variable="delta_Cl_rxn3" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaCl">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_rxn3" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k3</ci>
<ci>ENa</ci>
<ci>Cl</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k3_</ci>
<ci>ENaCl</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction4">
<variable units="millimolar" public_interface="in" name="ECl"/>
<variable units="millimolar" public_interface="in" name="Na"/>
<variable units="millimolar" public_interface="in" name="ENaCl"/>
<variable units="second_order_rate_constant" name="k4" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k4_" initial_value="8.940E4"/>
<variable units="flux" public_interface="out" name="delta_ECl_rxn4"/>
<variable units="flux" public_interface="out" name="delta_Na_rxn4"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_rxn4"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ECl">
<role stoichiometry="1" direction="forward" delta_variable="delta_ECl_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="Na">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_rxn4" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaCl">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_rxn4" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k4</ci>
<ci>ECl</ci>
<ci>Na</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k4_</ci>
<ci>ENaCl</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction5">
<variable units="millimolar" public_interface="in" name="E_i"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="ENa_i"/>
<variable units="second_order_rate_constant" name="k5" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k5_" initial_value="4.183E5"/>
<variable units="flux" public_interface="out" name="delta_E_i_rxn5"/>
<variable units="flux" public_interface="out" name="delta_Na_i_rxn5"/>
<variable units="flux" public_interface="out" name="delta_ENa_i_rxn5"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_i_rxn5" role="reactant"/>
</variable_ref>
<variable_ref variable="Na_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_i_rxn5" role="reactant"/>
</variable_ref>
<variable_ref variable="ENa_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_i_rxn5" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k5</ci>
<ci>E_i</ci>
<ci>Na_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k5_</ci>
<ci>ENa_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction6">
<variable units="millimolar" public_interface="in" name="E_i"/>
<variable units="millimolar" public_interface="in" name="Cl_i"/>
<variable units="millimolar" public_interface="in" name="ECl_i"/>
<variable units="second_order_rate_constant" name="k6" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k6_" initial_value="4.982E6"/>
<variable units="flux" public_interface="out" name="delta_E_i_rxn6"/>
<variable units="flux" public_interface="out" name="delta_Cl_i_rxn6"/>
<variable units="flux" public_interface="out" name="delta_ECl_i_rxn6"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_i_rxn6" role="reactant"/>
</variable_ref>
<variable_ref variable="Cl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_Cl_i_rxn6" role="reactant"/>
</variable_ref>
<variable_ref variable="ECl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ECl_i_rxn6" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k6</ci>
<ci>E_i</ci>
<ci>Cl_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k6_</ci>
<ci>ECl_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction7">
<variable units="millimolar" public_interface="in" name="ENa_i"/>
<variable units="millimolar" public_interface="in" name="Cl_i"/>
<variable units="millimolar" public_interface="in" name="ENaCl_i"/>
<variable units="second_order_rate_constant" name="k7" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k7_" initial_value="1.065E6"/>
<variable units="flux" public_interface="out" name="delta_ENa_i_rxn7"/>
<variable units="flux" public_interface="out" name="delta_Cl_i_rxn7"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_i_rxn7"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ENa_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_i_rxn7" role="reactant"/>
</variable_ref>
<variable_ref variable="Cl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_Cl_i_rxn7" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaCl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_i_rxn7" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k7</ci>
<ci>ENa_i</ci>
<ci>Cl_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k7_</ci>
<ci>ENaCl_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction8">
<variable units="millimolar" public_interface="in" name="ECl_i"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="ENaCl_i"/>
<variable units="second_order_rate_constant" name="k8" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k8_" initial_value="8.940E4"/>
<variable units="flux" public_interface="out" name="delta_ECl_i_rxn8"/>
<variable units="flux" public_interface="out" name="delta_Na_i_rxn8"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_i_rxn8"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ECl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ECl_i_rxn8" role="reactant"/>
</variable_ref>
<variable_ref variable="Na_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_i_rxn8" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaCl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_i_rxn8" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k8</ci>
<ci>ECl_i</ci>
<ci>Na_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k8_</ci>
<ci>ENaCl_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction9">
<variable units="millimolar" public_interface="in" name="E"/>
<variable units="millimolar" public_interface="in" name="E_i"/>
<variable units="first_order_rate_constant" name="k9" initial_value="4.587E5"/>
<variable units="first_order_rate_constant" name="k9_" initial_value="1.0E5"/>
<variable units="flux" public_interface="out" name="delta_E_i_rxn9"/>
<variable units="flux" public_interface="out" name="delta_E_rxn9"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_rxn9" role="reactant"/>
</variable_ref>
<variable_ref variable="E_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_i_rxn9" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k9</ci>
<ci>E</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k9_</ci>
<ci>E_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction10">
<variable units="millimolar" public_interface="in" name="ENaCl"/>
<variable units="millimolar" public_interface="in" name="ENaCl_i"/>
<variable units="first_order_rate_constant" name="k10" initial_value="1.0E3"/>
<variable units="first_order_rate_constant" name="k10_" initial_value="2.180E2"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_i_rxn10"/>
<variable units="flux" public_interface="out" name="delta_ENaCl_rxn10"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ENaCl">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_rxn10" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaCl_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaCl_i_rxn10" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k10</ci>
<ci>ENaCl</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k10_</ci>
<ci>ENaCl_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction11">
<variable units="millimolar" public_interface="in" name="ED"/>
<variable units="millimolar" public_interface="in" name="Na"/>
<variable units="millimolar" public_interface="in" name="ENaD"/>
<variable units="second_order_rate_constant" name="k11" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k11_" initial_value="4.183E5"/>
<variable units="flux" public_interface="out" name="delta_ED_rxn11"/>
<variable units="flux" public_interface="out" name="delta_Na_rxn11"/>
<variable units="flux" public_interface="out" name="delta_ENaD_rxn11"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ED">
<role stoichiometry="1" direction="forward" delta_variable="delta_ED_rxn11" role="reactant"/>
</variable_ref>
<variable_ref variable="Na">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_rxn11" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaD">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaD_rxn11" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k11</ci>
<ci>ED</ci>
<ci>Na</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k11_</ci>
<ci>ENaD</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction12">
<variable units="millimolar" public_interface="in" name="E"/>
<variable units="millimolar" public_interface="in" name="D"/>
<variable units="millimolar" public_interface="in" name="ED"/>
<variable units="second_order_rate_constant" name="k12" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k12_" initial_value="3.192E1"/>
<variable units="flux" public_interface="out" name="delta_E_rxn12"/>
<variable units="flux" public_interface="out" name="delta_D_rxn12"/>
<variable units="flux" public_interface="out" name="delta_ED_rxn12"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_rxn12" role="reactant"/>
</variable_ref>
<variable_ref variable="D">
<role stoichiometry="1" direction="forward" delta_variable="delta_D_rxn12" role="reactant"/>
</variable_ref>
<variable_ref variable="ED">
<role stoichiometry="1" direction="forward" delta_variable="delta_ED_rxn12" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k12</ci>
<ci>E</ci>
<ci>D</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k12_</ci>
<ci>ED</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction13">
<variable units="millimolar" public_interface="in" name="ENa"/>
<variable units="millimolar" public_interface="in" name="D"/>
<variable units="millimolar" public_interface="in" name="ENaD"/>
<variable units="second_order_rate_constant" name="k13" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k13_" initial_value="3.192E1"/>
<variable units="flux" public_interface="out" name="delta_ENa_rxn13"/>
<variable units="flux" public_interface="out" name="delta_D_rxn13"/>
<variable units="flux" public_interface="out" name="delta_ENaD_rxn13"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ENa">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_rxn13" role="reactant"/>
</variable_ref>
<variable_ref variable="D">
<role stoichiometry="1" direction="forward" delta_variable="delta_D_rxn13" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaD">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaD_rxn13" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k13</ci>
<ci>ENa</ci>
<ci>D</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k13_</ci>
<ci>ENaD</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction14">
<variable units="millimolar" public_interface="in" name="ED_i"/>
<variable units="millimolar" public_interface="in" name="Na_i"/>
<variable units="millimolar" public_interface="in" name="ENaD_i"/>
<variable units="second_order_rate_constant" name="k14" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k14_" initial_value="1.389E5"/>
<variable units="flux" public_interface="out" name="delta_ED_i_rxn14"/>
<variable units="flux" public_interface="out" name="delta_Na_i_rxn14"/>
<variable units="flux" public_interface="out" name="delta_ENaD_i_rxn14"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ED_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ED_i_rxn14" role="reactant"/>
</variable_ref>
<variable_ref variable="Na_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_Na_i_rxn14" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaD_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaD_i_rxn14" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k14</ci>
<ci>ED_i</ci>
<ci>Na_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k14_</ci>
<ci>ENaD_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction15">
<variable units="millimolar" public_interface="in" name="E_i"/>
<variable units="millimolar" public_interface="in" name="D_i"/>
<variable units="millimolar" public_interface="in" name="ED_i"/>
<variable units="second_order_rate_constant" name="k15" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k15_" initial_value="3.514E-1"/>
<variable units="flux" public_interface="out" name="delta_E_i_rxn15"/>
<variable units="flux" public_interface="out" name="delta_D_i_rxn15"/>
<variable units="flux" public_interface="out" name="delta_ED_i_rxn15"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="E_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_E_i_rxn15" role="reactant"/>
</variable_ref>
<variable_ref variable="D_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_D_i_rxn15" role="reactant"/>
</variable_ref>
<variable_ref variable="ED_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ED_i_rxn15" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k15</ci>
<ci>E_i</ci>
<ci>D_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k15_</ci>
<ci>ED_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<component name="reaction16">
<variable units="millimolar" public_interface="in" name="ENa_i"/>
<variable units="millimolar" public_interface="in" name="D_i"/>
<variable units="millimolar" public_interface="in" name="ENaD_i"/>
<variable units="second_order_rate_constant" name="k16" initial_value="1.0E8"/>
<variable units="first_order_rate_constant" name="k16_" initial_value="1.166E-1"/>
<variable units="flux" public_interface="out" name="delta_ENa_i_rxn16"/>
<variable units="flux" public_interface="out" name="delta_D_i_rxn16"/>
<variable units="flux" public_interface="out" name="delta_ENaD_i_rxn16"/>
<variable units="flux" name="rate"/>
<reaction reversible="yes">
<variable_ref variable="ENa_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENa_i_rxn16" role="reactant"/>
</variable_ref>
<variable_ref variable="D_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_D_i_rxn16" role="reactant"/>
</variable_ref>
<variable_ref variable="ENaD_i">
<role stoichiometry="1" direction="forward" delta_variable="delta_ENaD_i_rxn16" role="product"/>
</variable_ref>
<variable_ref variable="rate">
<role role="rate">
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci>rate</ci>
<apply>
<plus/>
<apply>
<times/>
<ci>k16</ci>
<ci>ENa_i</ci>
<ci>D_i</ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci>k16_</ci>
<ci>ENaD_i</ci>
</apply>
</apply>
</apply>
</apply>
</math>
</role>
</variable_ref>
</reaction>
</component>
<connection>
<map_components component_2="environment" component_1="E"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="E_i"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Na"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Na_i"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cl"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="Cl_i"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="D"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="D_i"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
<map_components component_2="environment" component_1="ENa"/>
<map_variables variable_2="time" variable_1="time"/>
</connection>
<connection>
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Intracellular Transporter-Thiazide Diuretics-Sodium Complex
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Extracellular Thiazide Diuretics
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Intracellular Transporter-Sodium Complex
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<vCard:Given>Catherine</vCard:Given>
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<vCard:Given>Toshiro</vCard:Given>
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Extracellular Transporter-Thiazide Diuretics Complex
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Extracellular Transporter-Sodium-Chloride Complex
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Extracellular Transporter-Thiazide Diuretics-Sodium Complex
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Extracellular Transporter-Chloride Complex
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Intracellular Transporter-Chloride Complex
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<dcterms:W3CDTF>2003-04-09</dcterms:W3CDTF>
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<vCard:Given>Hangil</vCard:Given>
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Intracellular Thiazide Diuretics
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<dcterms:W3CDTF>1999-06</dcterms:W3CDTF>
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Intracellular Transporter-Thiazide Diuretics Complex
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Chang and Fujita's 1999 kinetic model of the thiazide-sensitive Na-Cl cotransporter of the renal distal tubule.
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<cmeta:bio_entity>Renal Distal Tubule</cmeta:bio_entity>
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Extracellular Transporter-Sodium Complex
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<vCard:FN>Catherine Lloyd</vCard:FN>
</rdf:Description>
<rdf:Description rdf:about="#Na">
<dcterms:alternative>Extracellular Sodium</dcterms:alternative>
<dc:title>Na</dc:title>
</rdf:Description>
<rdf:Description rdf:about="#ENaCl_i">
<dcterms:alternative>
Intracellular Transporter-Sodium-Chloride Complex
</dcterms:alternative>
<dc:title>ENaCl_i</dc:title>
</rdf:Description>
<rdf:Description rdf:about="rdf:#ef2c6dbb-6a5b-4746-9b72-d9ccda577fb3">
<dcterms:W3CDTF>2003-01-20T00:00:00+00:00</dcterms:W3CDTF>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9ba215e1-7c97-4f60-8e15-f5e6304507f8">
<bqs:Pubmed_id>10362783</bqs:Pubmed_id>
<bqs:JournalArticle rdf:resource="rdf:#f7c04ac0-6b07-44ac-93e2-9823a5df0956"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#527c3f83-7d6c-4fd2-90f5-8dc4b5a25e9d">
<dcterms:modified rdf:resource="rdf:#96a3267b-1b5b-45f0-9b97-632ea50d9710"/>
<rdf:value>
Added publication date information.
</rdf:value>
<cmeta:modifier rdf:resource="rdf:#6e7e5423-06a7-4a79-bb48-6257696e00f8"/>
</rdf:Description>
<rdf:Description rdf:about="rdf:#9ecc027a-4cf3-4981-bbd3-120f5d8c5747">
<vCard:Given>Autumn</vCard:Given>
<vCard:Family>Cuellar</vCard:Family>
<vCard:Other>A</vCard:Other>
</rdf:Description>
</rdf:RDF>
</model>
