- Author:
- pmr2.import <nobody@models.cellml.org>
- Date:
- 2007-08-29 23:59:55+12:00
- Desc:
- committing version01 of chen_popel_2007
- Permanent Source URI:
- http://models.cellml.org/workspace/chen_popel_2007/rawfile/52c8f8c5995333ddb94bbfd97f4317b696351bf0/chen_popel_2007_a.cellml
<?xml version='1.0' encoding='utf-8'?>
<!-- FILE : chen_model_2007.xml
CREATED : 29th August 2007
LAST MODIFIED : 29th August 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 Chen and Popel's 2007 mathematical model of vascular and perivascular nitric oxide release and transport, which includes biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3).
CHANGES:
--><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="chen_model_2007" name="chen_popel_model_2007_version01">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Bioengineering Institute, University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
Nitric oxide (NO) plays an essential role in a diverse range of physiological and pathological processes, including acting as a potent vasodilator. NO can be synthesised in a reaction catalysed by the enzyme nitric oxide synthase (NOS), of which there are three isoforms: neuronal NOS (NOS1), inducible NOS (NOS2), and endothelial NOS (NOS3). The substrates required for NO synthesis include: L-arginine (Arg), oxygen (O2), and nicotinamide adenine dinucleotide phosphate (NADPH). Once NO is synthesised in the vasculature, it diffuses into the smooth muscle of the blood vessel walls, resulting in muscle relaxation and vasodilation. As such, NO derived from NOS3 has been considered as the main regulator of vascular tone. However, despite its physiological importance, there is a general lack of data on NO production and how its distribution changes around arterioles under different oxygen conditions, mainly due to experimental limitations.
</para>
<para>
In the study described here in CellML, Kejing Chen and Aleksander Popel produced a mathematical model to capture the characteristics of the biochemical pathway of neuronal nitric oxide synthase (NOS1). A schematic diagram of the reactions included in this model is outlined in the figure below.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="chen_model_2007.gif"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the mathematical model. Pathway of NO release and transport catalysed by neuronal nitric oxide synthase ((NOS1), here represented by the heme iron (Fe)). The heme ion of NOS1 binds L-arginine (Arg), hydroxyl-L-arginine (NOHA), and oxygen (O2), and undergoes a series of oxygenation and reduction reactions.</caption>
</informalfigure>
<para>
The complete original paper reference is cited below:
</para>
<para>
<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4MK02S3-6&_user=140507&_coverDate=03%2F15%2F2007&_rdoc=1&_fmt=summary&_orig=search&_cdi=4940&_sort=d&_docanchor=&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=96f7db54b7621a873f3fbc499b519847">Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)</ulink>, Kejing Chen and Aleksander S. Popel, 2007, <ulink url="http://www.sciencedirect.com/science/journal/08915849">
<emphasis>Free Radical Biology and Medicine</emphasis>
</ulink>, 42, 811-822. (<ulink url="http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6T38-4MK02S3-6&_user=140507&_coverDate=03%2F15%2F2007&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000011498&_version=1&_urlVersion=0&_userid=140507&md5=4b9500bab7dc680e01dfba9121618954#secx14">Full text</ulink> and PDF versions of the article are available to journal subscribers on the <emphasis>Free Radical Biology and Medicine</emphasis> website.) <ulink url="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&dopt=AbstractPlus&list_uids=17320763&query_hl=1&itool=pubmed_docsum">PubMed ID: 17320763</ulink>
</para>
</sect1>
</article>
</documentation>
<units name="micromolar">
<unit units="mole" prefix="micro"/>
<unit units="litre" exponent="-1"/>
</units>
<units name="first_order_rate_constant">
<unit units="second" exponent="-1"/>
</units>
<units name="second_order_rate_constant">
<unit units="second" exponent="-1"/>
<unit units="micromolar" exponent="-1"/>
</units>
<component name="environment">
<variable units="second" public_interface="out" name="time"/>
</component>
<component cmeta:id="Fe3" name="Fe3">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe3">
<dc:title>Fe3</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 3+)</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Fe3" initial_value="0.3"/>
<variable units="micromolar" public_interface="in" name="Arg"/>
<variable units="micromolar" public_interface="in" name="Fe3_Arg"/>
<variable units="micromolar" public_interface="in" name="Fe3_NO"/>
<variable units="micromolar" public_interface="in" name="Fe2_NO"/>
<variable units="micromolar" public_interface="in" name="O2"/>
<variable units="second_order_rate_constant" public_interface="in" name="k1"/>
<variable units="first_order_rate_constant" public_interface="in" name="k_1"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2"/>
<variable units="first_order_rate_constant" public_interface="in" name="k13"/>
<variable units="second_order_rate_constant" public_interface="in" name="k12"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="1">
<apply>
<eq/>
<apply>
<diff/>
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<ci>time</ci>
</bvar>
<ci> Fe3 </ci>
</apply>
<apply>
<minus/>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Fe3_Arg </ci>
</apply>
<apply>
<times/>
<ci> k13 </ci>
<ci> Fe3_NO </ci>
</apply>
<apply>
<times/>
<ci> k12 </ci>
<ci> Fe2_NO </ci>
<ci> O2 </ci>
</apply>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k1 </ci>
<ci> Arg </ci>
<ci> Fe3 </ci>
</apply>
<apply>
<times/>
<ci> k2 </ci>
<ci> Fe3 </ci>
</apply>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="Fe3_Arg" name="Fe3_Arg">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe3_Arg">
<dc:title>Fe3_Arg</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 3+) bound to L-arginine</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Fe3_Arg" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Arg"/>
<variable units="micromolar" public_interface="in" name="Fe3"/>
<variable units="second_order_rate_constant" public_interface="in" name="k1"/>
<variable units="first_order_rate_constant" public_interface="in" name="k_1"/>
<variable units="first_order_rate_constant" public_interface="in" name="k3"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="2">
<apply>
<eq/>
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<ci>time</ci>
</bvar>
<ci> Fe3_Arg </ci>
</apply>
<apply>
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<times/>
<ci> k1 </ci>
<ci> Fe3 </ci>
<ci> Arg </ci>
</apply>
<apply>
<plus/>
<apply>
<times/>
<ci> k_1 </ci>
<ci> Fe3_Arg </ci>
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<apply>
<times/>
<ci> k3 </ci>
<ci> Fe3_Arg </ci>
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</apply>
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</apply>
</math>
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<component cmeta:id="Fe2" name="Fe2">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe2">
<dc:title>Fe2</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 2+)</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Fe2" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Arg"/>
<variable units="micromolar" public_interface="in" name="Fe3"/>
<variable units="micromolar" public_interface="in" name="Fe2_Arg"/>
<variable units="first_order_rate_constant" public_interface="in" name="k2"/>
<variable units="first_order_rate_constant" public_interface="in" name="k_4"/>
<variable units="second_order_rate_constant" public_interface="in" name="k4"/>
<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="3">
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<ci>time</ci>
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<ci> k2 </ci>
<ci> Fe3 </ci>
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<times/>
<ci> k_4 </ci>
<ci> Fe2_Arg </ci>
</apply>
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<apply>
<times/>
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<ci> Arg </ci>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe2_Arg">
<dc:title>Fe2_Arg</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 2+) bound to L-arginine</dcterms:alternative>
</rdf:Description>
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<variable units="micromolar" public_interface="in" name="Arg"/>
<variable units="micromolar" public_interface="in" name="Fe3_Arg"/>
<variable units="micromolar" public_interface="in" name="Fe2"/>
<variable units="micromolar" public_interface="in" name="Fe3_O2_Arg"/>
<variable units="micromolar" public_interface="in" name="O2"/>
<variable units="second_order_rate_constant" public_interface="in" name="k4"/>
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<variable units="first_order_rate_constant" public_interface="in" name="k3"/>
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<variable units="second" public_interface="in" name="time"/>
<math xmlns="http://www.w3.org/1998/Math/MathML" id="4">
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<ci> k3 </ci>
<ci> Fe3_Arg </ci>
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<apply>
<times/>
<ci> k_5 </ci>
<ci> Fe3_O2_Arg </ci>
</apply>
<apply>
<times/>
<ci> k4 </ci>
<ci> Fe2 </ci>
<ci> Arg </ci>
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<apply>
<plus/>
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<times/>
<ci> k5 </ci>
<ci> Fe2_Arg </ci>
<ci> O2 </ci>
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<apply>
<times/>
<ci> k_4 </ci>
<ci> Fe2_Arg </ci>
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</component>
<component cmeta:id="Fe3_O2_Arg" name="Fe3_O2_Arg">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe3_O2_Arg">
<dc:title>Fe3_O2_Arg</dc:title>
<dcterms:alternative>oxidised neuronal nitric oxide synthase (heme iron 3+) bound to L-arginine</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Fe3_O2_Arg" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Fe2_Arg"/>
<variable units="micromolar" public_interface="in" name="O2"/>
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<math xmlns="http://www.w3.org/1998/Math/MathML" id="5">
<apply>
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<bvar>
<ci>time</ci>
</bvar>
<ci> Fe3_O2_Arg </ci>
</apply>
<apply>
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<times/>
<ci> k5 </ci>
<ci> Fe2_Arg </ci>
<ci> O2 </ci>
</apply>
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<times/>
<ci> k6 </ci>
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<apply>
<times/>
<ci> k_5 </ci>
<ci> Fe3_O2_Arg </ci>
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</component>
<component cmeta:id="Fe3_NOHA" name="Fe3_NOHA">
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe3_NOHA">
<dc:title>Fe3_NOHA</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 3+) bound to hydroxyl-L-arginine</dcterms:alternative>
</rdf:Description>
</rdf:RDF>
<variable units="micromolar" public_interface="out" name="Fe3_NOHA" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Fe3_O2_Arg"/>
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<math xmlns="http://www.w3.org/1998/Math/MathML" id="6">
<apply>
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<ci>time</ci>
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<apply>
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<ci> Fe3_NOHA </ci>
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</apply>
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</math>
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<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
<rdf:Description rdf:about="Fe2_NOHA">
<dc:title>Fe2_NOHA</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 2+) bound to hydroxyl-L-arginine</dcterms:alternative>
</rdf:Description>
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<variable units="micromolar" public_interface="out" name="Fe2_NOHA" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Fe2"/>
<variable units="micromolar" public_interface="in" name="Fe3_NOHA"/>
<variable units="micromolar" public_interface="in" name="NOHA"/>
<variable units="micromolar" public_interface="in" name="Fe3_O2_NOHA"/>
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<variable units="first_order_rate_constant" public_interface="in" name="k_9"/>
<variable units="first_order_rate_constant" public_interface="in" name="k_8"/>
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<dc:title>Fe3_O2_NOHA</dc:title>
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<ci> Fe3_O2_NOHA </ci>
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<rdf:Description rdf:about="Fe3_NO">
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<dcterms:alternative>neuronal nitric oxide synthase (heme iron 3+) bound to nitric oxide</dcterms:alternative>
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<ci> k11 </ci>
<ci> Fe3_NO </ci>
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<rdf:Description rdf:about="Fe2_NO">
<dc:title>Fe2_NO</dc:title>
<dcterms:alternative>neuronal nitric oxide synthase (heme iron 2+) bound to nitric oxide</dcterms:alternative>
</rdf:Description>
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<variable units="micromolar" public_interface="out" name="Fe2_NO" initial_value="0.0"/>
<variable units="micromolar" public_interface="in" name="Fe3_NO"/>
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<ci> k12 </ci>
<ci> Fe2_NO </ci>
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<rdf:Description rdf:about="NO">
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<variable units="micromolar" name="NO" initial_value="0.0"/>
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<rdf:RDF>
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<rdf:li>nitric oxide</rdf:li>
<rdf:li>nitric oxide synthase</rdf:li>
<rdf:li>signal transduction</rdf:li>
<rdf:li>cerebral aneurysm</rdf:li>
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<vCard:FN>Catherine Lloyd</vCard:FN>
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<dc:title>
Chen and Popel's 2007 mathematical model of vascular and perivascular nitric oxide release and transport, which includes biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3).
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<dc:publisher>The University of Auckland, Bioengineering Institute</dc:publisher>
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<vCard:Orgname>The University of Auckland</vCard:Orgname>
<vCard:Orgunit>The Bioengineering Institute</vCard:Orgunit>
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<dcterms:W3CDTF>2007-03-15</dcterms:W3CDTF>
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<dc:title>Vascular and perivascular nitric oxide release and transport: biochemical pathways of neuronal nitric oxide synthase (NOS1) and endothelial nitric oxide synthase (NOS3)</dc:title>
<bqs:volume>42</bqs:volume>
<bqs:first_page>811</bqs:first_page>
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<bqs:last_page>822</bqs:last_page>
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<vCard:Given>Kejing</vCard:Given>
<vCard:Family>Chen</vCard:Family>
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<dcterms:W3CDTF>2007-08-29T00:00:00+00:00</dcterms:W3CDTF>
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<dc:title>Free Radical Biology and Medicine</dc:title>
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<vCard:ORG rdf:resource="rdf:#da93257a-1c41-444a-950a-6470852ca810"/>
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<rdf:type rdf:resource="http://imc.org/vCard/3.0#internet"/>
<rdf:value>c.lloyd@auckland.ac.nz</rdf:value>
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<rdf:Description rdf:about="rdf:#a73568dc-861e-4b56-9ca1-0d1a3493f7a9">
<bqs:Pubmed_id>17320763</bqs:Pubmed_id>
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<vCard:FN>James Lawson</vCard:FN>
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<dc:creator rdf:resource="rdf:#fdf122fe-2d30-4f19-a6f3-345b1b5950f7"/>
<rdf:value>This model is known to run in PCEnv and COR and is known to be mathematically consistent with the publication it was based on.</rdf:value>
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<vCard:Given>Aleksander</vCard:Given>
<vCard:Family>Popel</vCard:Family>
<vCard:Other>S</vCard:Other>
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<rdf:Description rdf:about="rdf:#37817732-f091-4a18-99ec-55a726645349">
<vCard:Given>Catherine</vCard:Given>
<vCard:Family>Lloyd</vCard:Family>
<vCard:Other>May</vCard:Other>
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