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				<div class="dc:title">Martinez-Guimera2017 - Generic negative feedforward circuit (Model 5)</div>
				<div class="dc:bibliographicCitation">
					<p>This model is described in the article:</p>
					<div class="bibo:title">
						<a href="http://identifiers.org/pubmed/29146308" title="Access to this publication">'Molecular habituation' as a
    potential mechanism of gradual homeostatic loss with age.</a>
					</div>
					<div class="bibo:authorList">Martinez Guimera A, Welsh CM,
  Proctor CJ, McArdle A, Shanley DP.</div>
					<div class="bibo:Journal">Mech. Ageing Dev. 2017 Nov; :</div>
					<p>Abstract:</p>
					<div class="bibo:abstract">
						<p>The ability of reactive oxygen species (ROS) to cause
    molecular damage has meant that chronic oxidative stress has
    been mostly studied from the point of view of being a source of
    toxicity to the cell. However, the known duality of ROS
    molecules as both damaging agents and cellular redox signals
    implies another perspective in the study of sustained oxidative
    stress. This is a perspective of studying oxidative stress as a
    constitutive signal within the cell. In this work, we adopt a
    theoretical perspective as an exploratory and explanatory
    approach to examine how chronic oxidative stress can interfere
    with signal processing by redox signalling pathways in the
    cell. We report that constitutive signals can give rise to a
    'molecular habituation' effect that can prime for a gradual
    loss of biological function. This is because a constitutive
    signal in the environment has the potential to reduce the
    responsiveness of a signalling pathway through the prolonged
    activation of negative regulators. Additionally, we demonstrate
    how this phenomenon is likely to occur in different signalling
    pathways exposed to persistent signals and furthermore at
    different levels of biological organisation.</p>
					</div>
				</div>
				<div class="dc:publisher">
					<p>This model is hosted on 
  <a href="http://www.ebi.ac.uk/biomodels/">BioModels Database</a>
  and identified by: 
  <a href="http://identifiers.org/biomodels.db/MODEL1710260004">MODEL1710260004</a>.</p>
					<p>To cite BioModels Database, please use: 
  <a href="http://identifiers.org/pubmed/25414348" target="_blank">Chelliah V et al. BioModels: ten-year
  anniversary. Nucl. Acids Res. 2015, 43(Database
  issue):D542-8</a>.</p>
				</div>
				<div class="dc:license">
					<p>To the extent possible under law, all copyright and related or
  neighbouring rights to this encoded model have been dedicated to
  the public domain worldwide. Please refer to 
  <a href="http://creativecommons.org/publicdomain/zero/1.0/" title="Access to: CC0 1.0 Universal (CC0 1.0), Public Domain Dedication">CC0
  Public Domain Dedication</a> for more information.</p>
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										<dcterms:W3CDTF>2016-10-13T10:00:57Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="_89528fb0-4f88-45ac-870e-1f3fa1d6a6c7" species="A" stoichiometry="1"/>
					<speciesReference metaid="_779c76a3-c32e-4388-a49f-019aad69f217" species="N" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="c166d37a-9131-4a10-9ec3-23b189c3c179" species="N" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="_21598e12-ceb3-449d-83c6-2076ebebed29">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> A </ci>
							<ci> N </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="de82ccb4-1569-4ca9-a6b7-474b891bc0d7" name="k1" value="0.1"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
			<reaction id="reaction_9" sboTerm="SBO:0000171" metaid="COPASI13" name="reaction_9" reversible="false">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI13">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:01:40Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="f9e0e0cf-1df5-4a3a-8c2b-4e50661582cc" species="N" stoichiometry="1"/>
					<speciesReference metaid="f7baf5e0-e3b9-4556-ba48-4dd2cd95ad5c" species="Nil" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="f95617fb-3970-4ec6-98f5-ee421a6d3381" species="Nil" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="dad1c96b-682c-484d-b326-e3205378a51a">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> N </ci>
							<ci> Nil </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="_0eef03ff-1d3a-4c08-920b-70523fa9d548" name="k1" value="0.01"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
			<reaction id="reaction_10" sboTerm="SBO:0000171" metaid="COPASI14" name="reaction_10" reversible="false">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI14">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:26:24Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="_5f6a5c0a-3d80-49de-a728-98d6c8dbb2ed" species="O" stoichiometry="1"/>
					<speciesReference metaid="_45d6451b-1def-4b8a-832b-669918796f31" species="S2" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="_6feca10d-9f65-45d4-8e81-9d7cfc7cf12d" species="R" stoichiometry="1"/>
					<speciesReference metaid="_05638f41-373e-417b-8a5d-437f3669d9f8" species="O" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="_03aaef47-7e33-442c-b241-bfcdadc8a3b8">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> O </ci>
							<ci> S2 </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="bc2d0c47-3d72-4bb6-a198-3df9d27244f6" name="k1" value="0.1"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
			<reaction id="reaction_11" sboTerm="SBO:0000171" metaid="COPASI15" name="reaction_11" reversible="false">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI15">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:29:31Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="_2586f2d2-1f7e-484d-999a-8023ecb84b87" species="R" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="d75897b2-8466-4c76-88da-5b973f1137cb" species="N" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="_320b4b44-9222-4bfc-80c2-132da56072ea">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> R </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="_12acc37b-2b59-45b1-a4ca-9f318a97ce64" name="k1" value="0.1"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
			<reaction id="reaction_12" sboTerm="SBO:0000407" metaid="COPASI16" name="reaction_12" reversible="false">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI16">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:29:46Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="cf0e3f35-2f4b-4dc4-856c-dc62e77dcda9" species="Nil" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="_2501134c-c731-4e77-93ab-861172f31937" species="S2" stoichiometry="1"/>
					<speciesReference metaid="_48e702a8-4de5-4e98-aa6a-80c347d6d473" species="Nil" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="b57257a0-cf08-4dc5-97e9-e29c3d60a576">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> Nil </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="_1f37bf2c-3b74-4641-8016-f52d4e9c0784" name="k1" value="0.1"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
			<reaction id="reaction_13" sboTerm="SBO:0000407" metaid="COPASI17" name="reaction_13" reversible="false">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI17">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:30:21Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<listOfReactants>
					<speciesReference metaid="_032c9c52-658f-48a0-8879-40c2bd17e60e" species="S2" stoichiometry="1"/>
					<speciesReference metaid="_2f9a4b57-f7d6-4eec-84a9-a1fe12cbe014" species="Nil" stoichiometry="1"/>
				</listOfReactants>
				<listOfProducts>
					<speciesReference metaid="f386a8f9-50fe-4ccf-95e2-5077d805e43c" species="Nil" stoichiometry="1"/>
				</listOfProducts>
				<kineticLaw metaid="_336a6815-b783-4527-a1aa-9a072ed07d9d">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<times/>
							<ci> compartment </ci>
							<ci> k1 </ci>
							<ci> S2 </ci>
							<ci> Nil </ci>
						</apply>
					</math>
					<listOfParameters>
						<parameter id="k1" metaid="a40507eb-3e80-4259-9d59-3e106af2e9ca" name="k1" value="0.01"/>
					</listOfParameters>
				</kineticLaw>
			</reaction>
		</listOfReactions>
		<listOfEvents>
			<event id="event_1" metaid="COPASI4" name="event_1">
				<annotation>
					<COPASI xmlns="http://www.copasi.org/static/sbml">
						<rdf:RDF xmlns:dcterms="http://purl.org/dc/terms/" xmlns:rdf="http://www.w3.org/1999/02/22-rdf-syntax-ns#">
							<rdf:Description rdf:about="#COPASI4">
								<dcterms:created>
									<rdf:Description>
										<dcterms:W3CDTF>2016-10-13T10:02:55Z</dcterms:W3CDTF>
									</rdf:Description>
								</dcterms:created>
							</rdf:Description>
						</rdf:RDF>
					</COPASI>
				</annotation>
				<trigger metaid="_25bc74c8-98e2-4a88-b4aa-e7ca8486e8e4">
					<math xmlns="http://www.w3.org/1998/Math/MathML">
						<apply>
							<geq/>
							<csymbol encoding="text" definitionURL="http://www.sbml.org/sbml/symbols/time"> time </csymbol>
							<cn> 500 </cn>
						</apply>
					</math>
				</trigger>
				<listOfEventAssignments>
					<eventAssignment metaid="a85eab64-f9da-48a7-be9f-4f40874dea9f" variable="O">
						<math xmlns="http://www.w3.org/1998/Math/MathML">
							<cn> 100 </cn>
						</math>
					</eventAssignment>
				</listOfEventAssignments>
			</event>
		</listOfEvents>
	</model>
</sbml>
