beuke12

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Title

Authors

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Abstract

Journal

Unit definitions have no effect on the numerical analysis of the model. It remains the responsibility of the modeler to ensure the internal numerical consistency of the model. If units are provided, however, the consistency of the model units will be checked.

Name Definition
1e-06 litre
1e-12 mole
Id Name Spatial dimensions Size
EL EL 3.0 0.00000259
LSEC LSEC 3.0 0.00000047
MC MC 3.0 0.00000035
c1 nucleus 3.0 0.0000008
default cytoplasm 3.0 0.000013
Id Name Initial quantity Compartment Fixed
IkBa_cytoplasm IkBa 0.565355566147827 default (cytoplasm)
IkBa_mRNA_cytoplasm IkBa_mRNA 0.830719401662636 default (cytoplasm)
IkBa_mRNA_nucleus IkBa_mRNA 0.0000258591875100552 c1 (nucleus)
IkBa_pre_mRNA_1 IkBa_pre_mRNA_1 1.58904474538009 c1 (nucleus)
IkBa_pre_mRNA_2 IkBa_pre_mRNA_2 1.58904474538009 c1 (nucleus)
JNK JNK 0.952942675521268 default (cytoplasm)
JNK_P JNK_P 0.047057324478732 default (cytoplasm)
LPS LPS 5.0 EL (EL)
MSK1 MSK1 14.9703434361845 c1 (nucleus)
MSK1_P MSK1_P 0.0296565638154869 c1 (nucleus)
TNFR1_EL TNFR1 0.00122834645669291 EL (EL)
TNFR1_cytoplasm TNFR1 0.0000552755905511811 default (cytoplasm)
TNFa_TNFR1_EL TNFa:TNFR1 0.0 EL (EL)
TNFa_TNFR1_cytoplasm TNFa:TNFR1 0.0 default (cytoplasm)
TNFa_mRNA_LSEC TNFa_mRNA 0.0 LSEC (LSEC)
TNFa_mRNA_MC TNFa_mRNA 0.0 MC (MC)
TNFa_pre_mRNA_LSEC TNFa_pre_mRNA 0.0 LSEC (LSEC)
TNFa_pre_mRNA_MC TNFa_pre_mRNA 0.0 MC (MC)
p38 p38 0.737178298074244 default (cytoplasm)
p38_P p38_P 0.262821701925756 default (cytoplasm)
p65_2P p65_2P 0.224571815779822 c1 (nucleus)
p65_IkBa_nucleus p65-IkBa 0.849444166514529 c1 (nucleus)
p65_cytoplasm p65 0.000338847341182352 default (cytoplasm)
p65_mRNA p65_mRNA 1.0 default (cytoplasm)
p65_nucleus p65 0.0169379546715208 c1 (nucleus)
s11 IkBa 1.13071103598876 c1 (nucleus)
s14 IKKb 0.299995943221491 default (cytoplasm)
s15 IKKb_p 0.0000040567785089376 default (cytoplasm)
s16 TNFa 0.0 EL (EL)
s19 p65-IkBa 0.0424720958628244 default (cytoplasm)
s3 p65_P 0.00437952992503441 default (cytoplasm)
s5 IkBa_p 0.0743460803281643 default (cytoplasm)
s8 p65_P 0.2189570414411 c1 (nucleus)

Initial assignments are expressions that are evaluated at time=0. It is not recommended to create initial assignments for all model entities. Restrict the use of initial assignments to cases where a value is expressed in terms of values or sizes of other model entities. Note that it is not permitted to have both an initial assignment and an assignment rule for a single model entity.

Definition
Id Name Objective coefficient Reaction Equation and Kinetic Law Flux bounds
Complex_association_c Complex_association_c p65_cytoplasm + IkBa_cytoplasm = s19

default * (IkBa_p65_association_k * IkBa_cytoplasm * p65_cytoplasm - IkBa_p65_dissociation_k * s19)
Complex_degradation_IkBa_c Complex_degradation_IkBa_c s19 > p65_cytoplasm

default * IkBa_deg_complex_cyt_k * s19
Complex_degradation_IkBa_n Complex_degradation_IkBa_n p65_IkBa_nucleus > p65_nucleus

c1 * IkBa_deg_complex_nuc_k * p65_IkBa_nucleus
Complex_degradation_p65_c Complex_degradation_p65_c s19 > IkBa_cytoplasm

default * p65_degradation_k * s19
Complex_degradation_p65_n Complex_degradation_p65_n p65_IkBa_nucleus > s11

c1 * p65_degradation_k * p65_IkBa_nucleus
Complex_nuclear_shuttle Complex_nuclear_shuttle p65_IkBa_nucleus = s19

IkBa_p65_nuclear_export_k * p65_IkBa_nucleus - IkBa_p65_nuclear_import_k * s19
IKK_phosphorylation IKK_phosphorylation s14 > s15

default * Catalytic_activation__irrev(s14, TNFa_TNFR1_EL, IKKb_active_phosphorylation_kM, IKKb_active_phosphorylation_vmax, IKKb_active_phosphorylation_kA)
IkBa_degradation_c IkBa_degradation_c IkBa_cytoplasm > ∅

default * IkBa_deg_cyt_k * IkBa_cytoplasm
IkBa_degradation_n IkBa_degradation_n s11 > ∅

c1 * IkBa_deg_nuc_k * s11
IkBa_mRNA_degradation_c IkBa_mRNA_degradation_c IkBa_mRNA_cytoplasm > ∅

default * IkBa_mRNA_deg_cyt_k * IkBa_mRNA_cytoplasm
IkBa_mRNA_degradation_n IkBa_mRNA_degradation_n IkBa_mRNA_nucleus > ∅

c1 * IkBa_mRNA_deg_nuc_k * IkBa_mRNA_nucleus
IkBa_mRNA_transport IkBa_mRNA_transport IkBa_mRNA_nucleus > IkBa_mRNA_cytoplasm

IkBa_mRNA_transport_k * IkBa_mRNA_nucleus
IkBa_nuclear_shuttle IkBa_nuclear_shuttle IkBa_cytoplasm = s11

IkBa_nuclear_import_k * IkBa_cytoplasm - IkBa_nuclear_export_k * s11
IkBa_phosphorylation IkBa_phosphorylation IkBa_cytoplasm > s5

default * Henri_Michaelis_Menten__irreversible(IkBa_cytoplasm, IkBa_phosphorylation_kM, IkBa_phosphorylation_vmax)
IkBa_transcription_elongation_1 IkBa_transcription_elongation_1 IkBa_pre_mRNA_1 > IkBa_pre_mRNA_2

c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_1
IkBa_transcription_elongation_2 IkBa_transcription_elongation_2 IkBa_pre_mRNA_2 > IkBa_mRNA_nucleus

c1 * IkBa_transcription_elongation_kbasal * IkBa_pre_mRNA_2
IkBa_translation IkBa_translation IkBa_mRNA_cytoplasm > IkBa_mRNA_cytoplasm + IkBa_cytoplasm

default * Henri_Michaelis_Menten__irreversible(IkBa_mRNA_cytoplasm, IkBa_translation_Km, IkBa_translation_vmax)
JNK_active_phosphorylation JNK_active_phosphorylation JNK > JNK_P

default * Henri_Michaelis_Menten__irreversible(JNK, JNK_active_phoshorylation_Km, JNK_active_phosphorylation_vmax)
JNK_basal_phosphorylation JNK_basal_phosphorylation JNK > JNK_P

default * JNK_basal_phosphorylation_k * JNK
JNK_dephosphorylation JNK_dephosphorylation JNK_P > JNK

default * JNK_dephosphorylation_k * JNK_P
LPS_LSEC_degradation LPS_LSEC_degradation LPS > ∅

EL * LPS_LSEC_degradation_k * LPS
LPS_MC_degradation LPS_MC_degradation LPS > ∅

EL * LPS_MC_degradation_k * LPS
MSK1_activation MSK1_activation MSK1 > MSK1_P

c1 * Henri_Michaelis_Menten__irreversible(MSK1, MSK1_activation_kM, MSK1_activation_vmax)
MSK1_deactivation MSK1_deactivation MSK1_P > MSK1

c1 * MSK1_dephosphorylation_k * MSK1_P
TNFR1_shuttle TNFR1_shuttle TNFR1_cytoplasm = TNFR1_EL

k_TNFR1_vessicle2outer_membrane_shuttle * TNFR1_cytoplasm - k_TNFR1_outer_membrane2vessicle_shuttle * TNFR1_EL
TNFa_LSEC_transcription_elongation TNFa_LSEC_transcription_elongation TNFa_pre_mRNA_LSEC > TNFa_mRNA_LSEC

LSEC * TNFa_LSEC_transcription_elongation_k * TNFa_pre_mRNA_LSEC
TNFa_LSEC_transcription_initiation TNFa_LSEC_transcription_initiation ∅ > {2.0}TNFa_pre_mRNA_LSEC

LSEC * TNFa_transcription_initiation(TNFa_LSEC_transcription_initiation_kbasal, TNFa_LSEC_transcription_initiation_vA_LPS, LPS, TNFa_LSEC_transcription_initiation_kA_LPS)
TNFa_LSEC_translation TNFa_LSEC_translation TNFa_mRNA_LSEC > TNFa_mRNA_LSEC + s16

TNFa_LSEC_translation_k * TNFa_mRNA_LSEC
TNFa_MC_transcription_elongation TNFa_MC_transcription_elongation TNFa_pre_mRNA_MC > TNFa_mRNA_MC

MC * TNFa_MC_transcription_elongation_k * TNFa_pre_mRNA_MC
TNFa_MC_transcription_initiation TNFa_MC_transcription_initiation ∅ > {2.0}TNFa_pre_mRNA_MC

MC * TNFa_transcription_initiation(TNFa_MC_transcription_initiation_kbasal, TNFa_MC_transcription_initiation_vA_LPS, LPS, TNFa_MC_transcription_initiation_kA_LPS)
TNFa_MC_translation TNFa_MC_translation TNFa_mRNA_MC > TNFa_mRNA_MC + s16

TNFa_MC_translation_k * TNFa_mRNA_MC
TNFa_TNFR1_association TNFa:TNFR1_association TNFR1_EL + s16 = TNFa_TNFR1_EL

EL * (k_TNFa_TNFR1_association * TNFR1_EL * s16 - k_TNFa_TNFR1_dissociation * TNFa_TNFR1_EL)
TNFa_TNFR1_internalisation TNFa:TNFR1_internalisation TNFa_TNFR1_EL > TNFa_TNFR1_cytoplasm

k_TNFa_TNFR1_internalisation * TNFa_TNFR1_EL
TNFa_degradation TNFa degradation s16 > ∅

EL * TNFa_degradation_k * s16
TNFa_internal_degradation TNFa_internal_degradation TNFa_TNFR1_cytoplasm > TNFR1_cytoplasm

default * k_TNFa_internal_degradation * TNFa_TNFR1_cytoplasm
TNFa_mRNA_LSEC_degradation TNFa_mRNA_LSEC_degradation TNFa_mRNA_LSEC > ∅

LSEC * TNFa_mRNA_LSEC_degradation_k * TNFa_mRNA_LSEC
TNFa_mRNA_MC_degradation TNFa_mRNA_MC_degradation TNFa_mRNA_MC > ∅

MC * TNFa_mRNA_MC_degradation_k * TNFa_mRNA_MC
basal_IKKb_phosphorylation basal_IKKb_phosphorylation s14 > s15

default * IKKb_basal_phosphoylation_k * s14
p38_active_phosphorylation p38_active_phosphorylation p38 > p38_P

default * Henri_Michaelis_Menten__irreversible(p38, p38_active_phoshorylation_Km, p38_active_phosphorylation_vmax)
p38_basal_phosphorylation p38_basal_phosphorylation p38 > p38_P

default * p38_basal_phosphorylation_k * p38
p38_dephosphorylation p38_dephosphorylation p38_P > p38

default * p38_dephosphorylation_k * p38_P
p65_2P_degradation p65_2P_degradation p65_2P > ∅

c1 * p65_degradation_k * p65_2P
p65_2P_dephosphorylation_0 p65_2P_dephosphorylation p65_2P > p65_nucleus

c1 * p65_2P_dephosphorylation * p65_2P
p65_P_degradation_c p65_P_degradation_c s3 > ∅

default * p65_degradation_k * s3
p65_P_degradation_n p65_P_degradation_n s8 > ∅

c1 * p65_degradation_k * s8
p65_P_dephosphorylation_c p65_P_dephosphorylation_c s8 > p65_nucleus

c1 * p65_P_dephosphorylation_k * s8
p65_P_dephosphorylation_n p65_P_dephosphorylation_n s3 > p65_cytoplasm

default * p65_P_dephosphorylation_k * s3
p65_P_phosphorylation_MSK1 p65_P_phosphorylation_MSK1 s8 > p65_2P

c1 * Henri_Michaelis_Menten__irreversible(s8, p65_P_MSK1_phosphrylation_kM, p65_P_MSK1_phosphrylation_vmax)
p65_nuclear_shuttle p65_nuclear_shuttle p65_cytoplasm = p65_nucleus

p65_nuclear_import_k * p65_cytoplasm - p65_nuclear_export_k * p65_nucleus
p65_phosphorylation_MSK1 p65_phosphorylation_MSK1 p65_nucleus > p65_2P

c1 * Henri_Michaelis_Menten__irreversible(p65_nucleus, p65_MSK1_phosphorylation_kM, p65_MSK1_phosphrylation_vmax)
p65_translation p65_translation p65_mRNA > p65_mRNA + p65_cytoplasm

default * p65_translation_k * p65_mRNA
re10 IkBa_transcription_initiation ∅ > IkBa_pre_mRNA_1

c1 * activated_Transcription__1(IkBa_transcription_initiation_kbasal, IkBa_transcription_kA2_p65_P, s8, IkBa_transcription_kA_p65, p65_nucleus, p65_2P, IkBa_transcription_kA3_p65_2P)
re14 IkBa_p_active_degradation s5 > ∅

default * IkBa_p_active_degradation_k * s5
re15 Complex_phosphorylation s19 > s3 + s5

default * Henri_Michaelis_Menten__irreversible(s19, IkBa_p65_phosphorylation_kM, IkBa_p65_phosphorylation_vmax)
re17 dephosphorylation IKK s15 > s14

default * IKKb_dephopshorylation_k * s15
re19 Complex_association_n p65_nucleus + s11 = p65_IkBa_nucleus

c1 * (IkBa_p65_association_k * p65_nucleus * s11 - IkBa_p65_dissociation_k * p65_IkBa_nucleus)
re3 p65_P_nuclear_shuttle s3 = s8

p65_nuclear_import_k * s3 - p65_nuclear_export_k * s8

Global parameters

Id Value
IKKb_active_phosphorylation_kA 0.00100029725760187
IKKb_active_phosphorylation_kM 5.0
IKKb_active_phosphorylation_vmax 46.8635040429551
IKKb_basal_phosphoylation_k 0.00000350875584942235
IKKb_dephopshorylation_k 0.25947004951444
IkBa_deg_complex_cyt_k 0.00001
IkBa_deg_complex_nuc_k 0.0000100000000002221
IkBa_deg_cyt_k 0.0000100000000002221
IkBa_deg_nuc_k 0.00001
IkBa_mRNA_deg_cyt_k 0.000239451283552911
IkBa_mRNA_deg_nuc_k 0.00005
IkBa_mRNA_transport_k 0.0001
IkBa_nuclear_export_k 0.0025
IkBa_nuclear_import_k 0.005
IkBa_p65_association_k 0.0181250039035217
IkBa_p65_dissociation_k 0.0000543750117105651
IkBa_p65_nuclear_export_k 0.000100000000000222
IkBa_p65_nuclear_import_k 0.00199999999999978
IkBa_p65_phosphorylation_kM 0.5
IkBa_p65_phosphorylation_kcat 55.0206064117414
IkBa_p65_phosphorylation_vmax 0.000223206413639867
IkBa_p_active_degradation_k 0.00278609323177431
IkBa_phosphorylation_kM 0.1
IkBa_phosphorylation_kcat 55.0206064117414
IkBa_phosphorylation_vmax 0.000223206413639867
IkBa_transcription_elongation_kbasal 0.00203417791796864
IkBa_transcription_initiation_kbasal 0.000001
IkBa_transcription_kA2_p65_P 0.000100000000000222
IkBa_transcription_kA3_p65_2P 0.000100000000000222
IkBa_transcription_kA_p65 0.188160076455556
IkBa_translation_Km 2.54409019195356
IkBa_translation_vmax 0.000871132879896241
JNK_active_phoshorylation_Km 0.00100000000000022
JNK_active_phosphorylation_kcat 15458.1401560812
JNK_active_phosphorylation_vmax 0.0
JNK_basal_phosphorylation_k 0.0000358895493226871
JNK_dephosphorylation_k 0.000726787668735211
LPS_LSEC_degradation_k 0.000236929493170245
LPS_MC_degradation_k 0.000119823278896272
MSK1_activation_kM 0.332175
MSK1_activation_vmax 0.000262821701925698
MSK1_dephosphorylation_k 0.00866980333010383
MSK1_phosphorylation_kcat 0.000999999999999778
TNFa_LSEC_transcription_elongation_k 0.00000100000000022204
TNFa_LSEC_transcription_initiation_kA_LPS 1.06867411689223
TNFa_LSEC_transcription_initiation_kbasal 0.0
TNFa_LSEC_transcription_initiation_vA_LPS 0.0000121717455470529
TNFa_LSEC_translation_k 0.0000216062099370046
TNFa_MC_transcription_elongation_k 0.00000100000000022204
TNFa_MC_transcription_initiation_kA_LPS 0.821247967303126
TNFa_MC_transcription_initiation_kbasal 0.0
TNFa_MC_transcription_initiation_vA_LPS 0.00000585452703330464
TNFa_MC_translation_k 0.00000214522822741582
TNFa_degradation_k 0.000155649330244082
TNFa_mRNA_LSEC_degradation_k 0.594427650722179
TNFa_mRNA_MC_degradation_k 0.0518309763223509
k_IkBa 123003.053282154
k_IkBa_P 508267.65211444
k_IkBa_mRNA 33744.1815438661
k_JNK_P 1114598.39764676
k_MSK_P 27453716.3194485
k_TNFR1_outer_membrane2vessicle_shuttle 0.000018
k_TNFR1_vessicle2outer_membrane_shuttle 0.0004
k_TNFa_TNFR1_association 16.833
k_TNFa_TNFR1_dissociation 0.000319827
k_TNFa_TNFR1_internalisation 0.00077
k_TNFa_internal_degradation 0.0000893874256074768
k_p38_P 240885.605941937
k_p65 0.102372088824604
k_p65_P 2412261.75196443
p38_active_phoshorylation_Km 6.31699221824902
p38_active_phosphorylation_kcat 903645.196104721
p38_active_phosphorylation_vmax 0.0
p38_basal_phosphorylation_k 0.00023053564642347
p38_dephosphorylation_k 0.000646620405509385
p65_2P_dephosphorylation 0.000559922121253647
p65_MSK1_phosphorylation_kM 0.927382612068748
p65_MSK1_phosphrylation_kcat 0.0207741514841661
p65_MSK1_phosphrylation_vmax 0.000616089949202765
p65_P_MSK1_phosphrylation_kM 0.927382612068748
p65_P_MSK1_phosphrylation_kcat 0.0207741514841661
p65_P_MSK1_phosphrylation_vmax 0.000616089949202765
p65_P_dephosphorylation_k 0.000559922121253647
p65_degradation_k 0.00001328912101
p65_nuclear_export_k 0.00001
p65_nuclear_import_k 0.0005
p65_translation_k 0.00000168
scaled_IkBa 1.285675
scaled_IkBa_P 0.491240199999998
scaled_IkBa_mRNA 0.364416
scaled_JNK_P 0.681850240000002
scaled_MSK_P 0.651346312
scaled_p38_P 0.823029544
scaled_p65 0.000000170081493415978
scaled_p65_P 0.5598848
unscaled_IkBa 0.0000104523828124072
unscaled_IkBa_P 0.000000966499044266136
unscaled_IkBa_mRNA 0.0000107993729089643
unscaled_JNK_P 0.000000611745218223517
unscaled_MSK_P 0.0000000237252510523895
unscaled_p38_P 0.00000341668212503483
unscaled_p65 0.00000166140493340311
unscaled_p65_P 0.000000232099522178327

Local parameters

Id Value Reaction

Assignment rules

Definition
unscaled_JNK_P = default * JNK_P
JNK_active_phosphorylation_vmax = JNK_active_phosphorylation_kcat * TNFa_TNFR1_EL
scaled_p65_P = k_p65_P * unscaled_p65_P
scaled_IkBa_mRNA = k_IkBa_mRNA * unscaled_IkBa_mRNA
unscaled_IkBa_mRNA = IkBa_mRNA_cytoplasm * default + c1 * IkBa_mRNA_nucleus
unscaled_p65 = (s3 + s19 + p65_cytoplasm) * default + c1 * (s8 + p65_IkBa_nucleus + p65_nucleus + p65_2P)
unscaled_p65_P = c1 * s8 + default * s3
IkBa_phosphorylation_kcat = IkBa_p65_phosphorylation_kcat
p65_MSK1_phosphrylation_vmax = p65_MSK1_phosphrylation_kcat * MSK1_P
unscaled_IkBa = (s11 + p65_IkBa_nucleus) * c1 + (s5 + s19 + IkBa_cytoplasm) * default
p38_active_phosphorylation_vmax = p38_active_phosphorylation_kcat * TNFa_TNFR1_EL
p65_P_MSK1_phosphrylation_kcat = p65_MSK1_phosphrylation_kcat * 1.0
MSK1_activation_vmax = MSK1_phosphorylation_kcat * p38_P
p65_2P_dephosphorylation = p65_P_dephosphorylation_k * 1.0
p65_P_MSK1_phosphrylation_vmax = p65_P_MSK1_phosphrylation_kcat * MSK1_P
k_TNFa_TNFR1_dissociation = k_TNFa_TNFR1_association * 1.900000e-05
IkBa_p65_phosphorylation_vmax = IkBa_p65_phosphorylation_kcat * s15
p65_P_MSK1_phosphrylation_kM = p65_MSK1_phosphorylation_kM * 1.0
p65_nuclear_export_k = p65_nuclear_import_k * 0.02
IkBa_phosphorylation_vmax = IkBa_phosphorylation_kcat * s15
unscaled_MSK_P = c1 * MSK1_P
scaled_MSK_P = k_MSK_P * unscaled_MSK_P
unscaled_IkBa_P = s5 * default
scaled_IkBa_P = k_IkBa_P * unscaled_IkBa_P
scaled_p65 = k_p65 * unscaled_p65
IkBa_nuclear_export_k = IkBa_nuclear_import_k * 0.5
IkBa_p65_dissociation_k = IkBa_p65_association_k * 0.003
scaled_IkBa = k_IkBa * unscaled_IkBa
unscaled_p38_P = default * p38_P
scaled_p38_P = k_p38_P * unscaled_p38_P
scaled_JNK_P = k_JNK_P * unscaled_JNK_P

Rate rules

Definition

Algebraic rules

Definition
Definition
Catalytic_activation__irrev(substrate, Activator, Kms, V, Ka) = V * substrate * Activator / ((Kms + substrate) * (Ka + Activator))
Henri_Michaelis_Menten__irreversible(substrate, Km, V) = V * substrate / (Km + substrate)
activated_Transcription__1(k1, k2, Modifier, k3, Modifier2, Modifier3, k4) = k1 + k2 * Modifier + k3 * Modifier2 + k4 * Modifier3
TNFa_transcription_initiation(kbasal, vA, A, kA) = kbasal + vA * A / (A + kA)
Trigger Assignments