<?xml version="1.0" encoding="UTF-8"?>
<!--This biomodel was generated in VCML Version 0.4-->
<vcml xmlns="http://sourceforge.net/projects/vcell/vcml" Version="0.4">
   <BioModel Name="Vilar2006_TGFbeta">
      <Model Name="Vilar2006_TGFbeta">
         <ModelParameters>
            <Parameter Name="ka" Role="user defined" Unit="tbd">1.0</Parameter>
            <Parameter Name="ligand" Role="user defined" Unit="tbd">3.0E-5</Parameter>
            <Parameter Name="kcd" Role="user defined" Unit="tbd">0.0277777778</Parameter>
            <Parameter Name="klid" Role="user defined" Unit="tbd">0.25</Parameter>
            <Parameter Name="ki" Role="user defined" Unit="tbd">0.3333333333333</Parameter>
            <Parameter Name="pRI" Role="user defined" Unit="tbd">8.0</Parameter>
            <Parameter Name="kr" Role="user defined" Unit="tbd">0.0333333333333333</Parameter>
            <Parameter Name="alpha" Role="user defined" Unit="tbd">1.0</Parameter>
            <Parameter Name="pRII" Role="user defined" Unit="tbd">4.0</Parameter>
            <Parameter Name="VC_TimeConvFactor" Role="user defined" Unit="1">
               2.777777777777778E-4
               <Annotation>Conversion from SBML time units to VC time units</Annotation>
            </Parameter>
         </ModelParameters>
         <Compound Name="RI">
            <Annotation>RI</Annotation>
         </Compound>
         <Compound Name="RII">
            <Annotation>RII</Annotation>
         </Compound>
         <Compound Name="lRIRII">
            <Annotation>lRIRII</Annotation>
         </Compound>
         <Compound Name="lRIRII_endo">
            <Annotation>lRIRII_endo</Annotation>
         </Compound>
         <Compound Name="RI_endo">
            <Annotation>RI_endo</Annotation>
         </Compound>
         <Compound Name="RII_endo">
            <Annotation>RII_endo</Annotation>
         </Compound>
         <Feature Name="PM" />
         <Feature Name="Endosome" />
         <Membrane InsideFeature="Endosome" OutsideFeature="PM" MembraneVoltage="Voltage_Endosome_membrane" Name="Endosome_membrane" />
         <LocalizedCompound Name="RI" CompoundRef="RI" Structure="PM" OverrideName="true" />
         <LocalizedCompound Name="RII" CompoundRef="RII" Structure="PM" OverrideName="true" />
         <LocalizedCompound Name="lRIRII" CompoundRef="lRIRII" Structure="PM" OverrideName="true" />
         <LocalizedCompound Name="lRIRII_endo" CompoundRef="lRIRII_endo" Structure="Endosome" OverrideName="true" />
         <LocalizedCompound Name="RI_endo" CompoundRef="RI_endo" Structure="Endosome" OverrideName="true" />
         <LocalizedCompound Name="RII_endo" CompoundRef="RII_endo" Structure="Endosome" OverrideName="true" />
         <SimpleReaction Structure="PM" Name="v1" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Reactant LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Product LocalizedCompoundRef="lRIRII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * ka * ligand * RI * RI_ConcFactor * RII * RII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RI_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
               <Parameter Name="RII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v2" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="lRIRII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kcd * lRIRII * lRIRII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="lRIRII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v3" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="lRIRII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * klid * lRIRII * lRIRII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="lRIRII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v4" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="lRIRII" Stoichiometry="1" />
            <Product LocalizedCompoundRef="lRIRII_endo" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * ki * lRIRII * lRIRII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="lRIRII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v5" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Product LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(pRI * sbmlRateFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v6" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kcd * RI * RI_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RI_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v7" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RI_endo" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * ki * RI * RI_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RI_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v8" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RI_endo" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kr * RI_endo * RI_endo_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RI_endo_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v9" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="lRIRII_endo" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RI" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kr * lRIRII_endo * lRIRII_endo_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="lRIRII_endo_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v10" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Product LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(pRII * sbmlRateFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="PM" Name="v11" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kcd * RII * RII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v12" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RII_endo" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * ki * RII * RII_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RII_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <SimpleReaction Structure="Endosome_membrane" Name="v13" FluxCarrierValence="0" FluxOption="MolecularOnly">
            <Reactant LocalizedCompoundRef="RII_endo" Stoichiometry="1" />
            <Product LocalizedCompoundRef="RII" Stoichiometry="1" />
            <Kinetics KineticsType="GeneralLumpedKinetics">
               <Parameter Name="LumpedI" Role="lumped current" Unit="pA">0.0</Parameter>
               <Parameter Name="LumpedJ" Role="lumped reaction rate" Unit="molecules.s-1">(sbmlRateFactor * kr * RII_endo * RII_endo_ConcFactor)</Parameter>
               <Parameter Name="sbmlRateFactor" Role="user defined" Unit="3600.0 ">2.7777777777778E-4</Parameter>
               <Parameter Name="RII_endo_ConcFactor" Role="user defined" Unit="1.0E-15 ">6.0200000000000013E17</Parameter>
            </Kinetics>
         </SimpleReaction>
         <Diagram Name="PM" Structure="PM" />
         <Diagram Name="Endosome" Structure="Endosome" />
         <Diagram Name="Endosome_membrane" Structure="Endosome_membrane" />
      </Model>
      <SimulationSpec Name="Vilar2006_TGFbeta_Compartmental" Stochastic="false" UseConcentration="true">
         <Geometry Name="Compartmental" Dimension="0">
            <Extent X="10.0" Y="10.0" Z="10.0" />
            <Origin X="0.0" Y="0.0" Z="0.0" />
            <SubVolume Name="Compartment" Handle="0" Type="Compartmental" />
         </Geometry>
         <GeometryContext>
            <FeatureMapping Feature="PM" SubVolume="Compartment" Resolved="false" Size="1.0000000000000001E15">
               <BoundariesTypes Xm="Flux" Xp="Flux" Ym="Flux" Yp="Flux" Zm="Flux" Zp="Flux" />
            </FeatureMapping>
            <FeatureMapping Feature="Endosome" SubVolume="Compartment" Resolved="false" Size="1.0000000000000001E15">
               <BoundariesTypes Xm="Flux" Xp="Flux" Ym="Flux" Yp="Flux" Zm="Flux" Zp="Flux" />
            </FeatureMapping>
            <MembraneMapping Membrane="Endosome_membrane" SurfaceToVolumeRatio="4.835975862049403E-5" VolumeFraction="0.5" Size="4.835975862049403E10" CalculateVoltage="false" SpecificCapacitance="1.0" InitialVoltage="0.0" />
         </GeometryContext>
         <ReactionContext>
            <LocalizedCompoundSpec LocalizedCompoundRef="RI" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>3.322259136212625E-17</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <LocalizedCompoundSpec LocalizedCompoundRef="RII" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>3.322259136212625E-17</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <LocalizedCompoundSpec LocalizedCompoundRef="lRIRII" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>0.0</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <LocalizedCompoundSpec LocalizedCompoundRef="lRIRII_endo" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>6.64451827242525E-17</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <LocalizedCompoundSpec LocalizedCompoundRef="RI_endo" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>0.0</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <LocalizedCompoundSpec LocalizedCompoundRef="RII_endo" ForceConstant="false" EnableDiffusion="true">
               <InitialConcentration>0.0</InitialConcentration>
               <Diffusion>0.0</Diffusion>
            </LocalizedCompoundSpec>
            <ReactionSpec ReactionStepRef="v1" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v2" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v3" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v4" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v5" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v6" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v7" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v8" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v9" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v10" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v11" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v12" ReactionMapping="included" />
            <ReactionSpec ReactionStepRef="v13" ReactionMapping="included" />
         </ReactionContext>
         <BioEvents>
            <BioEvent Name="event_0000001">
               <Trigger>((t * VC_TimeConvFactor) &gt;= 2500.0)</Trigger>
               <EventAssignment Variable="ligand">0.01</EventAssignment>
            </BioEvent>
         </BioEvents>
      </SimulationSpec>
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