- Author:
- Catherine Lloyd <c.lloyd@auckland.ac.nz>
- Date:
- 2010-06-24 21:37:48+12:00
- Desc:
- Removed xml:base="" fromt the model file.
- Permanent Source URI:
- https://models.cellml.org/workspace/57f/rawfile/0a3138798f533ab5002cfa58fe734620029c089c/brown_choe_shanahan_czeisler_1997.cellml
<?xml version="1.0"?>
<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="brown_model_1997" name="brown_model_1997">
<documentation xmlns="http://cellml.org/tmp-documentation">
<article>
<articleinfo>
<title>A mathematical model of diurnal variations in human plasma melatonin levels</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
</author>
</articleinfo>
<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in OpenCell to recreate the published results. The units have been checked and they are consistent. The model also runs in COR but due to the time being in minutes and the simulation time being 3000 minutes long the model is not ideal for running in COR.
</para>
</section>
<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: Studies in animals and humans suggest that the diurnal pattern in plasma melatonin levels is due to the hormone's rates of synthesis, circulatory infusion and clearance, circadian control of synthesis onset and offset, environmental lighting conditions, and error in the melatonin immunoassay. A two-dimensional linear differential equation model of the hormone is formulated and is used to analyze plasma melatonin levels in 18 normal healthy male subjects during a constant routine. Recently developed Bayesian statistical procedures are used to incorporate correctly the magnitude of the immunoassay error into the analysis. The estimated parameters [median (range)] were clearance half-life of 23.67 (14.79-59.93) min, synthesis onset time of 2206 (1940-0029), synthesis offset time of 0621 (0246-0817), and maximum N-acetyltransferase activity of 7.17(2.34-17.93) pmol x l(-1) x min(-1). All were in good agreement with values from previous reports. The difference between synthesis offset time and the phase of the core temperature minimum was 1 h 15 min (-4 h 38 min-2 h 43 min). The correlation between synthesis onset and the dim light melatonin onset was 0.93. Our model provides a more physiologically plausible estimate of the melatonin synthesis onset time than that given by the dim light melatonin onset and the first reliable means of estimating the phase of synthesis offset. Our analysis shows that the circadian and pharmacokinetics parameters of melatonin can be reliably estimated from a single model.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
<mediaobject>
<imageobject>
<objectinfo>
<title>model diagram</title>
</objectinfo>
<imagedata fileref="brown_1997.png"/>
</imageobject>
</mediaobject>
<caption>Schematic diagram of the components and variables in a mathematical model of human melatonin. Diurnal rhythm of melatonin is observed in the plasma compartment. A represents N-acetylserotonin activity in the pineal gland, H1 is the concentration of melatonin in the pineal gland, beta_I is the plasma melatonin infusion rate, H2 is the plasma concentration of melatonin, and beta_C is the clearance rate of plasma melatonin.</caption>
</informalfigure>
<para>
The original paper reference is cited below:
</para>
<para>
A mathematical model of diurnal variations in human plasma melatonin levels, Emery N. Brown, Yong Choe, Theresa L. Shanahan, and Charles A. Czeisler, 1997, <emphasis>American Journal of Physiology; Endocrinology and Metabolism</emphasis>, 272, E506-E516. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/9124558">PubMed ID: 9124558</ulink>
</para>
</sect1>
</article>
</documentation>
<units name="minute">
<unit multiplier="60.0" units="second"/>
</units>
<units name="picomolar">
<unit prefix="pico" units="mole"/>
<unit exponent="-1" units="litre"/>
</units>
<units name="flux">
<unit units="picomolar"/>
<unit exponent="-1" units="minute"/>
</units>
<units name="first_order_rate_constant">
<unit exponent="-1" units="minute"/>
</units>
<component name="environment">
<variable cmeta:id="environment_time" name="time" public_interface="out" units="minute"/>
</component>
<component cmeta:id="H1" name="H1">
<variable cmeta:id="H1_H1" initial_value="0.05" name="H1" public_interface="out" units="picomolar"/>
<variable name="A" public_interface="in" units="flux"/>
<variable name="beta_I" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> H1 </ci>
</apply>
<apply>
<plus/>
<apply>
<minus/>
<apply>
<times/>
<ci> beta_I </ci>
<ci> H1 </ci>
</apply>
</apply>
<ci> A </ci>
</apply>
</apply>
</math>
</component>
<component cmeta:id="H2" name="H2">
<variable cmeta:id="H2_H2" initial_value="1.0" name="H2" public_interface="out" units="picomolar"/>
<variable name="H1" public_interface="in" units="picomolar"/>
<variable name="beta_I" public_interface="in" units="first_order_rate_constant"/>
<variable name="beta_C" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<apply>
<diff/>
<bvar>
<ci>time</ci>
</bvar>
<ci> H2 </ci>
</apply>
<apply>
<minus/>
<apply>
<times/>
<ci> beta_I </ci>
<ci> H1 </ci>
</apply>
<apply>
<times/>
<ci> beta_C </ci>
<ci> H2 </ci>
</apply>
</apply>
</apply>
</math>
</component>
<component cmeta:id="A" name="A">
<variable cmeta:id="A_A" name="A" public_interface="out" units="flux"/>
<variable initial_value="1316.0" name="t_on" units="minute"/>
<variable initial_value="1792.0" name="t_off" units="minute"/>
<variable initial_value="6.51" name="A_max" units="flux"/>
<variable name="alpha" public_interface="in" units="first_order_rate_constant"/>
<variable name="lamda" public_interface="in" units="first_order_rate_constant"/>
<variable name="time" public_interface="in" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> A </ci>
<piecewise>
<piece>
<apply>
<times/>
<ci> A_max </ci>
<apply>
<divide/>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> lamda </ci>
</apply>
<apply>
<minus/>
<ci> time </ci>
<ci> t_on </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<minus/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 1.0 </cn>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> lamda </ci>
</apply>
<apply>
<minus/>
<ci> t_off </ci>
<ci> t_on </ci>
</apply>
</apply>
</apply>
</apply>
</apply>
</apply>
<apply>
<and/>
<apply>
<lt/>
<ci> time </ci>
<ci> t_off </ci>
</apply>
<apply>
<geq/>
<ci> time </ci>
<ci> t_on </ci>
</apply>
</apply>
</piece>
<piece>
<apply>
<times/>
<ci> A_max </ci>
<apply>
<exp/>
<apply>
<times/>
<apply>
<minus/>
<ci> alpha </ci>
</apply>
<apply>
<minus/>
<ci> time </ci>
<ci> t_off </ci>
</apply>
</apply>
</apply>
</apply>
<apply>
<geq/>
<ci> time </ci>
<ci> t_off </ci>
</apply>
</piece>
<otherwise>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="flux"> 0.0 </cn>
</otherwise>
</piecewise>
</apply>
</math>
</component>
<component name="model_parameters">
<variable cmeta:id="model_parameters_beta_I" name="beta_I" public_interface="out" units="first_order_rate_constant"/>
<variable cmeta:id="model_parameters_beta_C" name="beta_C" public_interface="out" units="first_order_rate_constant"/>
<variable name="alpha" public_interface="out" units="first_order_rate_constant"/>
<variable name="lamda" public_interface="out" units="first_order_rate_constant"/>
<variable initial_value="2.82" name="tau_I" units="minute"/>
<variable initial_value="23.67" name="tau_C" units="minute"/>
<variable initial_value="25.92" name="tau_alpha" units="minute"/>
<variable initial_value="24.04" name="tau_lamda" units="minute"/>
<math xmlns="http://www.w3.org/1998/Math/MathML">
<apply>
<eq/>
<ci> beta_I </ci>
<apply>
<divide/>
<apply>
<ln/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> tau_I </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> beta_C </ci>
<apply>
<divide/>
<apply>
<ln/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> tau_C </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> alpha </ci>
<apply>
<divide/>
<apply>
<ln/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> tau_alpha </ci>
</apply>
</apply>
<apply>
<eq/>
<ci> lamda </ci>
<apply>
<divide/>
<apply>
<ln/>
<cn xmlns:cellml="http://www.cellml.org/cellml/1.0#" cellml:units="dimensionless"> 2.0 </cn>
</apply>
<ci> tau_lamda </ci>
</apply>
</apply>
</math>
</component>
<connection>
<map_components component_1="H1" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="H2" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="A" component_2="environment"/>
<map_variables variable_1="time" variable_2="time"/>
</connection>
<connection>
<map_components component_1="H1" component_2="A"/>
<map_variables variable_1="A" variable_2="A"/>
</connection>
<connection>
<map_components component_1="H1" component_2="model_parameters"/>
<map_variables variable_1="beta_I" variable_2="beta_I"/>
</connection>
<connection>
<map_components component_1="H2" component_2="H1"/>
<map_variables variable_1="H1" variable_2="H1"/>
</connection>
<connection>
<map_components component_1="H2" component_2="model_parameters"/>
<map_variables variable_1="beta_I" variable_2="beta_I"/>
<map_variables variable_1="beta_C" variable_2="beta_C"/>
</connection>
<connection>
<map_components component_1="A" component_2="model_parameters"/>
<map_variables variable_1="alpha" variable_2="alpha"/>
<map_variables variable_1="lamda" variable_2="lamda"/>
</connection>
<rdf:RDF xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#"><rdf:Description rdf:about="rdf:#8b2d1aed-1237-4b26-a6cd-a5a281544c99"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#ffb435c6-d748-42bd-8fa8-4f61e1786d78"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#30b56b71-0ed6-451e-9b3b-06997c5dd739"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family></rdf:Description><rdf:Description rdf:about="rdf:#c97a407b-a309-4728-a583-5d2b20c2b30e"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#7a3705a4-0387-427f-a9de-9658890547f0"/></creator><rdf:value xml:lang="en">This is the CellML description of Brown et al.'s 1997 mathematical model of diurnal variations in human plasma melatonin levels.</rdf:value></rdf:Description><rdf:Description rdf:about="rdf:#0eb58ca2-40da-4530-8b7a-f4885e5ee0c8"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">1997-03-00 00:00</W3CDTF></rdf:Description><rdf:Description rdf:about="#H1"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">melatonin concentration in the pineal gland</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">H1</title></rdf:Description><rdf:Description rdf:about="rdf:#3405314c-914e-42fd-9890-2c8bc2db9f93"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#30b56b71-0ed6-451e-9b3b-06997c5dd739"/></N><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#3d76844f-c04e-482c-80ac-c06c3fbf164e"/></EMAIL><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#83f0e524-8756-4d38-b3a1-b3946ba8aa2b"/></ORG></rdf:Description><rdf:Description rdf:about="rdf:#f7a1f067-9f56-4049-bcac-9f144808e28e"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Theresa</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">L</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Shanahan</Family></rdf:Description><rdf:Description rdf:about="rdf:#552acba1-ede2-4094-8673-57817816afe9"><Pubmed_id xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">9124558</Pubmed_id><JournalArticle xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#f070f5c2-0c0e-484a-8f0d-9f7e8ca5ffa4"/></JournalArticle></rdf:Description><rdf:Description rdf:about="rdf:#26e148ff-f34a-4b64-b731-77754099bd8f"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">James</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Richard</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lawson</Family></rdf:Description><rdf:Description rdf:about="rdf:#dd3c37a0-94a9-41ad-a100-531ddc0b7c07"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type><rdf:_2 xml:lang="en">melatonin</rdf:_2><rdf:_3 xml:lang="en">circadian</rdf:_3><rdf:_4 xml:lang="en">endocrine</rdf:_4><rdf:_1 xml:lang="en">pineal gland</rdf:_1></rdf:Description><rdf:Description rdf:about="rdf:#96b04ee8-dd80-4b7c-80a7-977e6057249f"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Charles</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">A</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Czeisler</Family></rdf:Description><rdf:Description rdf:about="rdf:#2ce8893c-77fa-49fc-8d1f-7c69fb1ebf5f"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#f7a1f067-9f56-4049-bcac-9f144808e28e"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#83f0e524-8756-4d38-b3a1-b3946ba8aa2b"><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Auckland Bioengineering Institute</Orgunit></rdf:Description><rdf:Description rdf:about="rdf:#27cfdfc7-d840-4e89-8a7a-24a8331ccdbe"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en"></FN></rdf:Description><rdf:Description rdf:about="#A"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">NAT activity</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">A</title></rdf:Description><rdf:Description rdf:about="rdf:#ffb435c6-d748-42bd-8fa8-4f61e1786d78"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Yong</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Choe</Family></rdf:Description><rdf:Description rdf:nodeID="n1"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n2"/></boundIntervals></rdf:Description><rdf:Description rdf:about="rdf:#f070f5c2-0c0e-484a-8f0d-9f7e8ca5ffa4"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#4d4b791f-e043-480f-8d83-0521b6455b9b"/></creator><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">A mathematical model of diurnal variations in human plasma melatonin levels</title><issued xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#0eb58ca2-40da-4530-8b7a-f4885e5ee0c8"/></issued><Journal xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#dc6d03e0-f42b-4d27-b1bf-8b35352edf20"/></Journal><volume xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">272</volume><first_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">E506</first_page><last_page xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">E516</last_page></rdf:Description><rdf:Description rdf:about="rdf:#3d76844f-c04e-482c-80ac-c06c3fbf164e"><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value></rdf:Description><rdf:Description rdf:about="rdf:#023d53f5-5cf1-4547-b103-1113048eee6a"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#26e148ff-f34a-4b64-b731-77754099bd8f"/></N></rdf:Description><rdf:Description rdf:about="rdf:#5240687d-1b09-42a5-acd9-edf2dcb305c6"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#96b04ee8-dd80-4b7c-80a7-977e6057249f"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="#brown_model_1997"><cmeta:bio_entity xml:lang="en">pineal gland</cmeta:bio_entity><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">
Brown et al.'s 1997 mathematical model of diurnal variations in human plasma melatonin levels.
</title><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#552acba1-ede2-4094-8673-57817816afe9"/></reference><reference xmlns="http://www.cellml.org/bqs/1.0#"><rdf:Description rdf:about="rdf:#be36f8c3-af63-44fd-a2cb-5d4616d25e44"/></reference><cmeta:comment><rdf:Description rdf:about="rdf:#c97a407b-a309-4728-a583-5d2b20c2b30e"/></cmeta:comment><simulation xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n1"/></simulation></rdf:Description><rdf:Description rdf:about="rdf:#dc6d03e0-f42b-4d27-b1bf-8b35352edf20"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">American Journal of Physiology; Endocrinology and Metabolism</title></rdf:Description><rdf:Description rdf:about=""><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#3405314c-914e-42fd-9890-2c8bc2db9f93"/></creator><cmeta:modification><rdf:Description rdf:about="rdf:#3f529174-b35c-46ad-9d71-ab66e0c0859d"/></cmeta:modification><publisher xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">The University of Auckland, Bioengineering Institute</publisher><cmeta:comment><rdf:Description rdf:about="rdf:#dbb7f1f3-b95b-4efb-9ecd-840699b02547"/></cmeta:comment><created xmlns="http://purl.org/dc/terms/"><rdf:Description rdf:about="rdf:#988393bd-f871-4209-b729-ed0a681b5da0"/></created></rdf:Description><rdf:Description rdf:nodeID="n3"><pointDensity xmlns="http://www.cellml.org/metadata/simulation/1.0#nonstandard-" xml:lang="en">100000</pointDensity><maximumStepSize xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">10</maximumStepSize><endingValue xmlns="http://www.cellml.org/metadata/simulation/1.0#" xml:lang="en">3000</endingValue></rdf:Description><rdf:Description rdf:about="rdf:#988393bd-f871-4209-b729-ed0a681b5da0"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2007-07-06T00:00:00+00:00</W3CDTF></rdf:Description><rdf:Description rdf:about="rdf:#4d4b791f-e043-480f-8d83-0521b6455b9b"><rdf:type><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Seq"/></rdf:type><rdf:_2><rdf:Description rdf:about="rdf:#8b2d1aed-1237-4b26-a6cd-a5a281544c99"/></rdf:_2><rdf:_3><rdf:Description rdf:about="rdf:#2ce8893c-77fa-49fc-8d1f-7c69fb1ebf5f"/></rdf:_3><rdf:_4><rdf:Description rdf:about="rdf:#5240687d-1b09-42a5-acd9-edf2dcb305c6"/></rdf:_4><rdf:_1><rdf:Description rdf:about="rdf:#3e046bd6-49f2-4ce2-9024-51d5fbdaa7fd"/></rdf:_1></rdf:Description><rdf:Description rdf:about="rdf:#18a56bf8-4dd3-4736-be4e-d5a3ad712d34"><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Emery</Given><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">N</Other><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Brown</Family></rdf:Description><rdf:Description rdf:about="rdf:#dbb7f1f3-b95b-4efb-9ecd-840699b02547"><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#27cfdfc7-d840-4e89-8a7a-24a8331ccdbe"/></creator><rdf:value xml:lang="en"></rdf:value></rdf:Description><rdf:Description rdf:about="rdf:#3e046bd6-49f2-4ce2-9024-51d5fbdaa7fd"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#18a56bf8-4dd3-4736-be4e-d5a3ad712d34"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#be36f8c3-af63-44fd-a2cb-5d4616d25e44"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#3c842afa-8ef8-47e3-bee8-72e7fa7e08ac"/></subject></rdf:Description><rdf:Description rdf:about="rdf:#3f529174-b35c-46ad-9d71-ab66e0c0859d"><cmeta:modifier><rdf:Description rdf:about="rdf:#023d53f5-5cf1-4547-b103-1113048eee6a"/></cmeta:modifier></rdf:Description><rdf:Description rdf:about="#H2"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">melatonin concentration in the plasma</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">H2</title></rdf:Description><rdf:Description rdf:about="rdf:#7a3705a4-0387-427f-a9de-9658890547f0"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="rdf:#3c842afa-8ef8-47e3-bee8-72e7fa7e08ac"><rdf:value><rdf:Description rdf:about="rdf:#dd3c37a0-94a9-41ad-a100-531ddc0b7c07"/></rdf:value><subject_type xmlns="http://www.cellml.org/bqs/1.0#" xml:lang="en">keyword</subject_type></rdf:Description><rdf:Description rdf:nodeID="n2"><rdf:first><rdf:Description rdf:nodeID="n3"/></rdf:first><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest></rdf:Description></rdf:RDF></model>
