<?xml version="1.0"?>
<!-- FILE : kyrylov_model_2005.xml
CREATED : 11th July 2007
LAST MODIFIED : 11th July 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 Kyrylov et al's 2005 mathematical model of oscillatory behaviour of the hypothalamic-pituitary-adrenal axis.
CHANGES:
-->
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<title>Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis</title>
<author>
<firstname>Catherine</firstname>
<surname>Lloyd</surname>
<affiliation>
<shortaffil>Auckland Bioengineering Institute, The University of Auckland</shortaffil>
</affiliation>
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<section id="sec_status">
<title>Model Status</title>
<para>
This CellML model runs in OpenCell, PCEnv and COR, and the units are consistent throughout. The model does not quite recreate the published results (although the output is similar), part of the reason for this might be that the original model uses reset rules to define injections of additional hormones, which is not a supported feature in CellML at present.
</para>
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<sect1 id="sec_structure">
<title>Model Structure</title>
<para>
ABSTRACT: A mathematical model of the hypothalamic-pituitary-adrenal (HPA) axis of the human endocrine system is proposed. This new model provides an improvement over previous models by introducing two nonlinear factors with physiological relevance: 1) a limit to gland size; 2) rejection of negative hormone concentrations. The result is that the new model is by far the most robust; e.g., it can tolerate at least -50% and +100% perturbations to any of its parameters. This high degree of robustness allows one, for the first time, to model features of the system such as circadian rhythm and response to hormone injections. In addition, relative to its closest predecessor, the model is simpler; it contains only about half of the parameters, and yet achieves more functions. The new model provides opportunities for teaching endocrinology within a biological or medical school context; it may also have applications in modeling and studying HPA axis disorders, for example, related to gland size dynamics, abnormal hormone levels, or stress influences.
</para>
<informalfigure float="0" id="fig_reaction_diagram">
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<caption>Schematic diagram of the hypothalamus-pituitary-adrenal (HPA) axis. Stimulatory and inhibitory paths are indicated by the arrows and + or - signs respectively. CRH represents corticotropin-releasing hormone, ACTH is corticotropin, and CBG represents corticosteroid-binding globulin.</caption>
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<para>
The original paper reference is cited below:
</para>
<para>
Modeling robust oscillatory behavior of the hypothalamic-pituitary-adrenal axis, Vadim Kyrylov, Liudmila A. Severyanova, and Amandio Vieira, 2005, <emphasis>IEEE Transactions on Biomedical Engineering</emphasis>, 52, 1977-1983. <ulink url="http://www.ncbi.nlm.nih.gov/pubmed/16366221">PubMed ID: 16366221</ulink>
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rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#Bag"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#42924936-cce4-4e50-8f67-17c98151efdf"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="rdf:#6f6bf0cd-1d85-42f4-85dd-f5ccbdf0cc75"><FN xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine Lloyd</FN></rdf:Description><rdf:Description rdf:about="#y1"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">ACTH</alternative><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">corticotropin</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">y1</title></rdf:Description><rdf:Description rdf:about="rdf:#db593a92-1f53-4d3a-831e-4cf25b8a1aef"><rdf:value xml:lang="en">This is a CellML description of Kyrylov et al's 2005 mathematical model of oscillatory behaviour of the hypothalamic-pituitary-adrenal axis.</rdf:value><creator 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axis</title></rdf:Description><rdf:Description rdf:about="rdf:#8cf5dcef-003c-45f4-a95b-2df614bf5c19"><Other xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">May</Other><Given xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Catherine</Given><Family xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">Lloyd</Family></rdf:Description><rdf:Description rdf:about="rdf:#0c84abfc-e07e-448b-a7f1-2c870b28f6fd"><ORG xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#1c65ddcf-ea9e-4c7b-8e52-5500eb2db2bf"/></ORG><EMAIL xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#6f70947a-2cea-442a-bdc7-1877f985b19b"/></EMAIL><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#8cf5dcef-003c-45f4-a95b-2df614bf5c19"/></N></rdf:Description><rdf:Description rdf:about="rdf:#9f6597f4-ddf4-4fea-b8bb-3af715d46bb4"><W3CDTF xmlns="http://purl.org/dc/terms/" 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Kyrylov et al's 2005 mathematical model of oscillatory behaviour of the hypothalamic-pituitary-adrenal axis.
</title></rdf:Description><rdf:Description rdf:about="rdf:#6f70947a-2cea-442a-bdc7-1877f985b19b"><rdf:value xml:lang="en">c.lloyd@auckland.ac.nz</rdf:value><rdf:type><rdf:Description rdf:about="http://imc.org/vCard/3.0#internet"/></rdf:type></rdf:Description><rdf:Description rdf:about="#y4"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">CBG-bound cortisol</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">y4</title></rdf:Description><rdf:Description rdf:about="#y3"><alternative xmlns="http://purl.org/dc/terms/" xml:lang="en">albumin-bound cortisol</alternative><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">y3</title></rdf:Description><rdf:Description rdf:nodeID="n2"><boundIntervals xmlns="http://www.cellml.org/metadata/simulation/1.0#"><rdf:Description rdf:nodeID="n3"/></boundIntervals></rdf:Description><rdf:Description rdf:about="rdf:#52328131-a68d-42d1-b7b5-faa5e2a53fc3"><title xmlns="http://purl.org/dc/elements/1.1/" xml:lang="en">IEEE Transactions on Biomedical Engineering</title></rdf:Description><rdf:Description rdf:nodeID="n3"><rdf:first><rdf:Description rdf:nodeID="n1"/></rdf:first><rdf:rest><rdf:Description rdf:about="http://www.w3.org/1999/02/22-rdf-syntax-ns#nil"/></rdf:rest></rdf:Description><rdf:Description rdf:about="rdf:#4fcf1924-7987-409a-aa2d-a046e2512720"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#632de3c2-4cec-4702-b755-98e9c9450fe2"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#c110f01e-3453-48fe-92d1-c20e7e005150"><subject xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#ae459f0c-9ee3-471d-a5d1-1fd22bf5e70b"/></subject></rdf:Description><rdf:Description rdf:about="rdf:#1c65ddcf-ea9e-4c7b-8e52-5500eb2db2bf"><Orgunit xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The Bioengineering Institute</Orgunit><Orgname xmlns="http://www.w3.org/2001/vcard-rdf/3.0#" xml:lang="en">The University of Auckland</Orgname></rdf:Description><rdf:Description rdf:about="rdf:#b27724a7-f898-44c2-8d20-d5c2fcf76043"><N xmlns="http://www.w3.org/2001/vcard-rdf/3.0#"><rdf:Description rdf:about="rdf:#2569a5cd-ef52-4d96-8269-c2bf6bf9ab63"/></N><rdf:type><rdf:Description rdf:about="http://www.cellml.org/bqs/1.0#Person"/></rdf:type></rdf:Description><rdf:Description rdf:about="rdf:#c1d6204d-5fe7-4ed0-8aee-720c58192cf2"><rdf:value xml:lang="en">This version of the HPA axis model runs in PCEnv to recreate the results published in the paper.</rdf:value><creator xmlns="http://purl.org/dc/elements/1.1/"><rdf:Description rdf:about="rdf:#6f6bf0cd-1d85-42f4-85dd-f5ccbdf0cc75"/></creator></rdf:Description><rdf:Description rdf:about="rdf:#075e657b-1e64-4650-b701-19347fdf2123"><W3CDTF xmlns="http://purl.org/dc/terms/" xml:lang="en">2005-12-00 00:00</W3CDTF></rdf:Description></rdf:RDF></model>
