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BIOMD0000000332 - Bungay2006_Plasma

 

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Reference Publication
Publication ID: 16838084
Bungay SD, Gentry PA, Gentry RD.
Modelling thrombin generation in human ovarian follicular fluid.
Bull. Math. Biol. 2006 Nov; 68(8): 2283-2302
Department of Applied Mathematics, University of Waterloo, Waterloo, Ontario, Canada N2L 3G1. sharene@cs.mun.ca  [more]
Model
Original Model: BIOMD0000000332.origin
Submitter: Michael Schubert
Submission ID: MODEL1105090001
Submission Date: 09 May 2011 15:46:18 UTC
Last Modification Date: 28 May 2014 13:15:02 UTC
Creation Date: 12 May 2011 12:58:49 UTC
Encoders:  Nick Juty
   Vijayalakshmi Chelliah
   Michael Schubert
set #1
bqbiol:occursIn Brenda Tissue Ontology blood plasma
set #2
bqbiol:hasTaxon Taxonomy Homo sapiens
set #3
bqbiol:hasProperty Mathematical Modelling Ontology MAMO_0000046
set #4
bqbiol:isVersionOf Gene Ontology blood coagulation
set #5
bqmodel:isDerivedFrom BioModels Database Bungay2003_Thrombin_Generation
Notes

This model is from the article:
Modelling thrombin generation in human ovarian follicular fluid
Bungay Sharene D., Gentry Patricia A., Gentry Rodney D. Bulletin of Mathematical BiologyVolume 68, Issue 8, 12 July 2006, Pages 2283-302 16838084,
Abstract:
A mathematical model is constructed to study thrombin production in human ovarian follicular fluid. The model results show that the amount of thrombin that can be produced in ovarian follicular fluid is much lower than that in blood plasma, failing to reach the level required for fibrin formation, and thereby supporting the hypothesis that in follicular fluid thrombin functions to initiate cellular activities via intracellular signalling receptors. It is also concluded that the absence of the amplification pathway to thrombin production in follicular fluid is a major factor in restricting the amount of thrombin that can be produced. Titration of the initial concentrations of the various reactants in the model lead to predictions for the amount of tissue factor and phospholipid that is required to maintain thrombin production in the follicle, as well as to the conclusion that tissue factor pathway inhibitor has little effect on the time that thrombin generation is sustained. Numerical experiments to determine the effect of factor V, which is at a much reduced level in follicular fluid compared to plasma, and thrombomodulin, illustrate the importance for further experimental work to determine values for several parameters that have yet to be reported in the literature.

Model
Publication ID: 16838084 Submission Date: 09 May 2011 15:46:18 UTC Last Modification Date: 28 May 2014 13:15:02 UTC Creation Date: 12 May 2011 12:58:49 UTC
Mathematical expressions
Reactions
Factor II lipid binding Factor mIIa lipid binding Factor V lipid binding Factor Va lipid binding
Factor VII lipid binding Factor VIIa lipid binding Factor VIII lipid binding Factor VIIIa lipid binding
Factor IX lipid binding Factor IXa lipid binding Factor X lipid binding Factor Xa lipid binding
APC lipid binding PS lipid binding Factor VIIIai lipid binding Factor Vai lipid binding
PC lipid binding TF_VIIa binding TF_VII binding IX_TF_VIIa binding
Factor IX activation X_TF_VIIa complex formation Factor X activation Factor Xa release
Xa_TF_VII binding TF_VII activation VIIIa_IXa binding Va_Xa binding
X_IXa_VIIIa complex formation Factor X activation V_Xa binding Factor V activation
Xa_VIII binding Factor VIII activation R11 R11b
R12 R12b R13 R14
R15 R15b R16 R16b
R17 R17b R18 R18b
R19 R19b R20 R21
R22 R23 R24 R25
R25b R26 R26b R27
R28 R28b R29 R30
R31 R31b R32 R33
R34      
Physical entities
Compartments Species
Cell II_f II_l mIIa_f
mIIa_l V_f V_l
Va_f Va_l VII_f
VII_l VIIa_f VIIa_l
VIII_f VIII_l VIIIa_f
VIIIa_l IX_f IX_l
IXa_f IXa_l X_f
X_l Xa_f Xa_l
APC_f APC_l PS_f
PS_l VIIIai_f VIIIai_l
Vai_f Vai_l PC_f
PC_l TF_l TF_VIIa_l
TF_VII_l TF_VIIa_IX_l TF_VIIa_IXa_l
TF_VIIa_X_l TF_VIIa_Xa_l TF_VII_Xa_l
IXa_VIIIa_l Xa_Va_l IXa_VIIIa_X_l
V_Xa_l VIII_Xa_l IIa_f
V_IIa_l VIII_IIa_l Xa_Va_II_l
Xa_Va_mIIa_l XI_f XI_IIa_l
XIa_l APC_PS_l APC_PS_VIIIa_l
TFPI_f AT_f IIa_AT_f
TFPI_Xa_l TFPI_Xa_TF_VIIa_l APC_PS_Va_l
IXa_AT_f Xa_AT_f VII_Xa_l
V_mIIa_l VIII_mIIa_l TM_l
IIa_TM_l IIa_TM_PC_l mIIa_AT_l
XIa_IX_l LIPID alpha2M_l
alpha2M_IIa_l alpha2M_Xa_l AT_XIa_l
Global parameters
konII nva koffII konmIIa
koffmIIa konV koffV konVa
koffVa konVII koffVII konVIIa
koffVIIa konVIII koffVIII konVIIIa
koffVIIIa konIX koffIX konIXa
koffIXa konX koffX konXa
koffXa konAPC koffAPC konPS
koffPS konVIIIai koffVIIIai konVai
koffVai konPC koffPC k1
k2 k3 k4 k5
k6 k7 k8 k9
k10 k11 k12 k13
k14 k15 k16 k17
k18 k19 k20 k21
k22 k23 k24 k25
k26 k27 k28 k29
k30 k31 k32 k33
k34 k35 k36 k37
k38 k39 k40 k41
k42 k43 k44 k45
k46 k47 k48 k49
k50 k51 k52 k53
k54 k55 k56 k57
k58 k59 k60 k61
k62 k63 k64 k65
k66 k67 k68 k69
k70 k71 k72 k73
k74 k75 k76 k77
k78      
Reactions (69)
 
 Factor II lipid binding [II_f] + 100.0 × [LIPID] → [II_l];  
 
 Factor mIIa lipid binding [mIIa_f] + 100.0 × [LIPID] → [mIIa_l];  
 
 Factor V lipid binding [V_f] + 100.0 × [LIPID] → [V_l];  
 
 Factor Va lipid binding [Va_f] + 100.0 × [LIPID] → [Va_l];  
 
 Factor VII lipid binding [VII_f] + 100.0 × [LIPID] → [VII_l];  
 
 Factor VIIa lipid binding [VIIa_f] + 100.0 × [LIPID] → [VIIa_l];  
 
 Factor VIII lipid binding [VIII_f] + 100.0 × [LIPID] → [VIII_l];  
 
 Factor VIIIa lipid binding [VIIIa_f] + 100.0 × [LIPID] → [VIIIa_l];  
 
 Factor IX lipid binding [IX_f] + 100.0 × [LIPID] → [IX_l];  
 
 Factor IXa lipid binding [IXa_f] + 100.0 × [LIPID] → [IXa_l];  
 
 Factor X lipid binding [X_f] + 100.0 × [LIPID] → [X_l];  
 
 Factor Xa lipid binding [Xa_f] + 100.0 × [LIPID] → [Xa_l];  
 
 APC lipid binding [APC_f] + 100.0 × [LIPID] → [APC_l];  
 
 PS lipid binding [PS_f] + 100.0 × [LIPID] → [PS_l];  
 
 Factor VIIIai lipid binding [VIIIai_f] + 100.0 × [LIPID] → [VIIIai_l];  
 
 Factor Vai lipid binding [Vai_f] + 100.0 × [LIPID] → [Vai_l];  
 
 PC lipid binding [PC_f] + 100.0 × [LIPID] → [PC_l];  
 
 TF_VIIa binding [VIIa_l] + [TF_l] → [TF_VIIa_l];  
 
 TF_VII binding [VII_l] + [TF_l] → [TF_VII_l];  
 
 IX_TF_VIIa binding [IX_l] + [TF_VIIa_l] → [TF_VIIa_IX_l];  
 
 Factor IX activation [TF_VIIa_IX_l] → [TF_VIIa_l] + [IXa_l];  
 
 X_TF_VIIa complex formation [X_l] + [TF_VIIa_l] → [TF_VIIa_X_l];  
 
 Factor X activation [TF_VIIa_X_l] → [TF_VIIa_Xa_l];  
 
 Factor Xa release [TF_VIIa_Xa_l] → [Xa_l] + [TF_VIIa_l];  
 
 Xa_TF_VII binding [Xa_l] + [TF_VII_l] → [TF_VII_Xa_l];  
 
 TF_VII activation [TF_VII_Xa_l] → [Xa_l] + [TF_VIIa_l];  
 
 VIIIa_IXa binding [VIIIa_l] + [IXa_l] → [IXa_VIIIa_l];  
 
 Va_Xa binding [Va_l] + [Xa_l] → [Xa_Va_l];  
 
 X_IXa_VIIIa complex formation [X_l] + [IXa_VIIIa_l] → [IXa_VIIIa_X_l];  
 
 Factor X activation [IXa_VIIIa_X_l] → [Xa_l] + [IXa_VIIIa_l];  
 
 V_Xa binding [Xa_l] + [V_l] → [V_Xa_l];  
 
 Factor V activation [V_Xa_l] → [Xa_l] + [Va_l];  
 
 Xa_VIII binding [Xa_l] + [VIII_l] → [VIII_Xa_l];  
 
 Factor VIII activation [VIII_Xa_l] → [Xa_l] + [VIIIa_l];  
 
 R11 [IIa_f] + [V_l] → [V_IIa_l];  
 
 R11b [V_IIa_l] → [IIa_f] + [Va_l];  
 
 R12 [IIa_f] + [VIII_l] → [VIII_IIa_l];  
 
 R12b [VIII_IIa_l] → [IIa_f] + [VIIIa_l];  
 
 R13 [II_l] + [Xa_Va_l] → [Xa_Va_II_l];  
 
 R14 [mIIa_l] + [Xa_Va_l] → [Xa_Va_mIIa_l];  
 
 R15 [Xa_Va_II_l] → [Xa_Va_mIIa_l];  
 
 R15b [Xa_Va_mIIa_l] → [IIa_f] + [Xa_Va_l] + 100.0 × [LIPID];  
 
 R16 [Xa_l] + [VII_l] → [VII_Xa_l];  
 
 R16b [VII_Xa_l] → [Xa_l] + [VIIa_l];  
 
 R17 [IIa_f] + [XI_f] → [XI_IIa_l];  
 
 R17b [XI_IIa_l] → [IIa_f] + [XIa_l];  
 
 R18 [VIIIa_l] + [APC_PS_l] → [APC_PS_VIIIa_l];  
 
 R18b [APC_PS_VIIIa_l] → [VIIIai_l] + [APC_PS_l];  
 
 R19 [Va_l] + [APC_PS_l] → [APC_PS_Va_l];  
 
 R19b [APC_PS_Va_l] → [Vai_l] + [APC_PS_l];  
 
 R20 [Xa_f] + [TFPI_f] → [TFPI_Xa_l];  
 
 R21 [TF_VIIa_l] + [TFPI_Xa_l] → [TFPI_Xa_TF_VIIa_l];  
 
 R22 [AT_f] + [IXa_f] → [IXa_AT_f];  
 
 R23 [AT_f] + [Xa_f] → [Xa_AT_f];  
 
 R24 [AT_f] + [IIa_f] → [IIa_AT_f];  
 
 R25 [mIIa_l] + [V_l] → [V_mIIa_l];  
 
 R25b [V_mIIa_l] → [mIIa_l] + [Va_l];  
 
 R26 [mIIa_l] + [VIII_l] → [VIII_mIIa_l];  
 
 R26b [VIII_mIIa_l] → [mIIa_l] + [VIIIa_l];  
 
 R27 [TM_l] + [IIa_f] → [IIa_TM_l];  
 
 R28 [PC_l] + [IIa_TM_l] → [IIa_TM_PC_l];  
 
 R28b [IIa_TM_PC_l] → [APC_l] + [IIa_TM_l];  
 
 R29 [AT_f] + [mIIa_f] → [mIIa_AT_l];  
 
 R30 [PS_l] + [APC_l] → [APC_PS_l];  
 
 R31 [IX_l] + [XIa_l] → [XIa_IX_l];  
 
 R31b [XIa_IX_l] → [IXa_l] + [XIa_l];  
 
 R32 [AT_f] + [XIa_l] → [AT_XIa_l];  
 
 R33 [alpha2M_l] + [IIa_f] → [alpha2M_IIa_l];  
 
 R34 [alpha2M_l] + [Xa_f] → [alpha2M_Xa_l];  
 
 Cell Spatial dimensions: 3.0  Compartment size: 1.0
 
 II_f
Compartment: Cell
Initial concentration: 1400.0
 
 II_l
Compartment: Cell
Initial concentration: 0.0
 
 mIIa_f
Compartment: Cell
Initial concentration: 0.0
 
 mIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 V_f
Compartment: Cell
Initial concentration: 20.0
 
 V_l
Compartment: Cell
Initial concentration: 0.0
 
 Va_f
Compartment: Cell
Initial concentration: 0.0
 
 Va_l
Compartment: Cell
Initial concentration: 0.0
 
 VII_f
Compartment: Cell
Initial concentration: 10.0
 
 VII_l
Compartment: Cell
Initial concentration: 0.0
 
 VIIa_f
Compartment: Cell
Initial concentration: 0.1
 
 VIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 VIII_f
Compartment: Cell
Initial concentration: 0.7
 
 VIII_l
Compartment: Cell
Initial concentration: 0.0
 
 VIIIa_f
Compartment: Cell
Initial concentration: 0.0
 
 VIIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 IX_f
Compartment: Cell
Initial concentration: 90.0
 
 IX_l
Compartment: Cell
Initial concentration: 0.0
 
 IXa_f
Compartment: Cell
Initial concentration: 0.0
 
 IXa_l
Compartment: Cell
Initial concentration: 0.0
 
 X_f
Compartment: Cell
Initial concentration: 170.0
 
 X_l
Compartment: Cell
Initial concentration: 0.0
 
 Xa_f
Compartment: Cell
Initial concentration: 0.0
 
 Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 APC_f
Compartment: Cell
Initial concentration: 0.0
 
 APC_l
Compartment: Cell
Initial concentration: 0.0
 
 PS_f
Compartment: Cell
Initial concentration: 300.0
 
 PS_l
Compartment: Cell
Initial concentration: 0.0
 
 VIIIai_f
Compartment: Cell
Initial concentration: 0.0
 
 VIIIai_l
Compartment: Cell
Initial concentration: 0.0
 
 Vai_f
Compartment: Cell
Initial concentration: 0.0
 
 Vai_l
Compartment: Cell
Initial concentration: 0.0
 
 PC_f
Compartment: Cell
Initial concentration: 60.0
 
 PC_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_l
Compartment: Cell
Initial concentration: 0.005
 
 TF_VIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VII_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VIIa_IX_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VIIa_IXa_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VIIa_X_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VIIa_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 TF_VII_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 IXa_VIIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 Xa_Va_l
Compartment: Cell
Initial concentration: 0.0
 
 IXa_VIIIa_X_l
Compartment: Cell
Initial concentration: 0.0
 
 V_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 VIII_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 IIa_f
Compartment: Cell
Initial concentration: 0.0
 
 V_IIa_l
Compartment: Cell
Initial concentration: 0.0
 
 VIII_IIa_l
Compartment: Cell
Initial concentration: 0.0
 
 Xa_Va_II_l
Compartment: Cell
Initial concentration: 0.0
 
 Xa_Va_mIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 XI_f
Compartment: Cell
Initial concentration: 30.0
 
 XI_IIa_l
Compartment: Cell
Initial concentration: 0.0
 
 XIa_l
Compartment: Cell
Initial concentration: 0.0
 
 APC_PS_l
Compartment: Cell
Initial concentration: 0.0
 
 APC_PS_VIIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 TFPI_f
Compartment: Cell
Initial concentration: 2.5
 
 AT_f
Compartment: Cell
Initial concentration: 3400.0
 
 IIa_AT_f
Compartment: Cell
Initial concentration: 0.0
 
 TFPI_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 TFPI_Xa_TF_VIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 APC_PS_Va_l
Compartment: Cell
Initial concentration: 0.0
 
 IXa_AT_f
Compartment: Cell
Initial concentration: 0.0
 
 Xa_AT_f
Compartment: Cell
Initial concentration: 0.0
 
 VII_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 V_mIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 VIII_mIIa_l
Compartment: Cell
Initial concentration: 0.0
 
 TM_l
Compartment: Cell
Initial concentration: 1.0
 
 IIa_TM_l
Compartment: Cell
Initial concentration: 0.0
 
 IIa_TM_PC_l
Compartment: Cell
Initial concentration: 0.0
 
 mIIa_AT_l
Compartment: Cell
Initial concentration: 0.0
 
 XIa_IX_l
Compartment: Cell
Initial concentration: 0.0
 
 LIPID
Compartment: Cell
Initial concentration: 170000.0
 
 alpha2M_l
Compartment: Cell
Initial concentration: 2600.0
 
 alpha2M_IIa_l
Compartment: Cell
Initial concentration: 0.0
 
 alpha2M_Xa_l
Compartment: Cell
Initial concentration: 0.0
 
 AT_XIa_l
Compartment: Cell
Initial concentration: 0.0
 
Global Parameters (113)
 
   konII
Value: 0.0043
Constant
 
   nva
Value: 100.0
Constant
 
   koffII
Value: 1.0
Constant
 
   konmIIa
Value: 0.05
Constant
 
   koffmIIa
Value: 0.475
Constant
 
   konV
Value: 0.05
Constant
 
   koffV
Value: 0.145
Constant
 
   konVa
Value: 0.057
Constant
 
   koffVa
Value: 0.17
Constant
 
   konVII
Value: 0.05
Constant
 
   koffVII
Value: 0.66
Constant
 
   konVIIa
Value: 0.05
Constant
 
   koffVIIa
Value: 0.227
Constant
 
   konVIII
Value: 0.05
Constant
 
   koffVIII
Value: 0.1
Constant
 
   konVIIIa
Value: 0.05
Constant
 
   koffVIIIa
Value: 0.335
Constant
 
   konIX
Value: 0.05
Constant
 
   koffIX
Value: 0.115
Constant
 
   konIXa
Value: 0.05
Constant
 
   koffIXa
Value: 0.115
Constant
 
   konX
Value: 0.01
Constant
 
   koffX
Value: 1.9
Constant
 
   konXa
Value: 0.029
Constant
 
   koffXa
Value: 3.3
Constant
 
   konAPC
Value: 0.05
Constant
 
   koffAPC
Value: 3.5
Constant
 
   konPS
Value: 0.05
Constant
 
   koffPS
Value: 0.2
Constant
 
   konVIIIai
Value: 0.05
Constant
 
   koffVIIIai
Value: 0.335
Constant
 
   konVai
Value: 0.057
Constant
 
   koffVai
Value: 0.17
Constant
 
   konPC
Value: 0.05
Constant
 
   koffPC
Value: 11.5
Constant
 
   k1
Value: 0.5
Constant
 
   k2
Value: 0.005
Constant
 
   k3
Value: 0.005
Constant
 
   k4
Value: 0.005
Constant
 
   k5
Value: 0.01
Constant
 
   k6
Value: 2.09
Constant
 
   k7
Value: 0.34
Constant
 
   k8
Value: 0.1
Constant
 
   k9
Value: 32.5
Constant
 
   k10
Value: 1.5
Constant
 
   k11
Value: 0.05
Constant
 
   k12
Value: 44.8
Constant
 
   k13
Value: 15.2
Constant
 
   k14
Value: 0.1
Constant
 
   k15
Value: 0.2
Constant
 
   k16
Value: 1.0
Constant
 
   k17
Value: 1.0
Constant
 
   k18
Value: 0.1
Constant
 
   k19
Value: 10.7
Constant
 
   k20
Value: 8.3
Constant
 
   k21
Value: 0.1
Constant
 
   k22
Value: 1.0
Constant
 
   k23
Value: 0.043
Constant
 
   k24
Value: 0.1
Constant
 
   k25
Value: 2.1
Constant
 
   k26
Value: 0.023
Constant
 
   k27
Value: 0.1
Constant
 
   k28
Value: 6.94
Constant
 
   k29
Value: 0.23
Constant
 
   k30
Value: 0.1
Constant
 
   k31
Value: 13.8
Constant
 
   k32
Value: 0.9
Constant
 
   k33
Value: 0.1
Constant
 
   k34
Value: 100.0
Constant
 
   k35
Value: 0.1
Constant
 
   k36
Value: 66.0
Constant
 
   k37
Value: 13.0
Constant
 
   k38
Value: 15.0
Constant
 
   k39
Value: 0.05
Constant
 
   k40
Value: 44.8
Constant
 
   k41
Value: 15.2
Constant
 
   k42
Value: 0.1
Constant
 
   k43
Value: 10.0
Constant
 
   k44
Value: 1.43
Constant
 
   k45
Value: 0.1
Constant
 
   k46
Value: 1.6
Constant
 
   k47
Value: 0.4
Constant
 
   k48
Value: 0.1
Constant
 
   k49
Value: 1.6
Constant
 
   k50
Value: 0.4
Constant
 
   k51
Value: 0.016
Constant
 
   k52
Value: 3.3E-4
Constant
 
   k53
Value: 0.01
Constant
 
   k54
Value: 0.0011
Constant
 
   k55
Value: 4.9E-7
Constant
 
   k56
Value: 2.3E-6
Constant
 
   k57
Value: 6.83E-6
Constant
 
   k58
Value: 0.1
Constant
 
   k59
Value: 6.94
Constant
 
   k60
Value: 1.035
Constant
 
   k61
Value: 0.1
Constant
 
   k62
Value: 13.8
Constant
 
   k63
Value: 0.9
Constant
 
   k64
Value: 1.0
Constant
 
   k65
Value: 0.5
Constant
 
   k66
Value: 0.1
Constant
 
   k67
Value: 6.4
Constant
 
   k68
Value: 3.6
Constant
 
   k69
Value: 6.83E-6
Constant
 
   k70
Value: 0.1
Constant
 
   k71
Value: 0.5
Constant
 
   k72
Value: 0.01
Constant
 
   k73
Value: 1.417
Constant
 
   k74
Value: 0.183
Constant
 
   k75
Value: 1.0
Constant
 
   k76
Value: 2.3E-6
Constant
 
   k77
Value: 2.5E-6
Constant
 
   k78
Value: 1.4E-6
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000332

Curator's comment: (updated: 12 May 2011 13:53:14 BST)

Blood plasma model of the Article Bungay2006 (follicular fluid model also available in MODEL1105090000). It is a modification of Bungay2003 (MODEL9852292468). Factors are denoted by their numbers, with _l and _f suffixes depending on whether they are lipid-bound or fluid phase.

Thrombin generation curve in blood plasma as depicted by figure 3b of the article. Model integrated and simulated in Copasi 4.6.32, plotted with Matplotlib.

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