BioModelsapplication/xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=curation_notes.txthttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367.pdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367-biopax2.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367-biopax3.owlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367_url.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=manifest.xmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367.odehttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367-matlab.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367-octave.mhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=metadata.rdfhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367_url.sedmlhttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=curation_image.pnghttps://www.ebi.ac.uk/biomodels/model/download/BIOMD0000000367?filename=BIOMD0000000367.sciprimaryOK200Michael SchubertManually curatedordinary differential equation modelCoronary Artery DiseaseL2V4https://www.ebi.ac.uk/biomodels/BIOMD000000036717936855falseBioModelsModelsSBMLMueller2008 ThrombinGeneration minimal2008MODEL1108260013Johannes MüllerJohannes Müller, Stefan Brandt, Katrin Mayerhofer, Thorsten Tjardes, Marc Maegele17936855, This paper focus on the quest for mechanisms that are able to create tolerance and an activation threshold in the extrinsic coagulation cascade. We propose that the interplay of coagulation inhibitor and blood flow creates threshold behavior. First we test this hypothesis in a minimal, four dimensional model. This model can be analysed by means of time scale analysis. We find indeed that only the interplay of blood flow and inhibition together are able to produce threshold behavior. The mechanism relays on a combination of raw substance supply and wash-out effect by the blood flow and a stabilization of the resting state by the inhibition. We use the insight into this minimal model to interpret the simulation results of a large model. Here, we find that the initiating steps (TF that produces together with fVII(a) factor Xa) does not exhibit threshold behavior, but the overall system does. Hence, the threshold behavior appears via the feedback loop (in that fIIa produces indirectly fXa that in turn produces fIIa again) inhibited by ATIII and blood flow.. 2, 211. Technical University Munich, Centre for Mathematical Sciences, Boltzmannstr. 3, D-85748 Garching/Munich, Germany. johannes.mueller@gsf.deschubert@ebi.ac.ukEBIBIOMD0000000367This paper focus on the quest for mechanisms that are able to create tolerance and an activation threshold in the extrinsic coagulation cascade. We propose that the interplay of coagulation inhibitor and blood flow creates threshold behavior. First we test this hypothesis in a minimal, four dimensional model. This model can be analysed by means of time scale analysis. We find indeed that only the interplay of blood flow and inhibition together are able to produce threshold behavior. The mechanism relays on a combination of raw substance supply and wash-out effect by the blood flow and a stabilization of the resting state by the inhibition. We use the insight into this minimal model to interpret the simulation results of a large model. Here, we find that the initiating steps (TF that produces together with fVII(a) factor Xa) does not exhibit threshold behavior, but the overall system does. Hence, the threshold behavior appears via the feedback loop (in that fIIa produces indirectly fXa that in turn produces fIIa again) inhibited by ATIII and blood flow.Tolerance and threshold in the extrinsic coagulation system.Müller Johannes J, Brandt Stefan S, Mayerhofer Katrin K, Tjardes Thorsten T, Maegele Marc MfalseMueller2008_ThrombinGeneration_minimal This model originates from BioModels Database: A Database of Annotated Published Models (http://www.ebi.ac.uk/biomodels/). It is copyright (c) 2005-2011 The BioModels.net Team. For more information see the terms of use. To cite BioModels Database, please use: Li C, Donizelli M, Rodriguez N, Dharuri H, Endler L, Chelliah V, Li L, He E, Henry A, Stefan MI, Snoep JL, Hucka M, Le Novère N, Laibe C (2010) BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. BMC Syst Biol., 4:92. 2024-08-212024-09-022011-08-26BIOMD000000036717936855MODEL1108260013BIOMD0000000367GO:00075962759