1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/14609719.csml convertedTime:2009.07.01.10:42

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Molecular mechanisms of macrophage activation and deactivation bylipopolysaccharide: roles of the receptor complex.
Authors Fujihara M, Muroi M, Tanamoto K, Suzuki T, Azuma H, Ikeda H.
Affiliation Japanese Red Cross, Hokkaido Red Cross Blood Center, Yamanote 2-2, Nishi-ku,Sapporo 063-0002, Japan. fujihara@hokkaido.bc.jrc.or.jp
Abstract Bacterial lipopolysaccharide (LPS), the major structural component of the outerwall of Gram-negative bacteria, is a potent activator of macrophages. Activatedmacrophages produce a variety of inflammatory cytokines. Excessive production ofcytokines in response to LPS is regarded as the cause of septic shock. On theother hand, macrophages exposed to suboptimal doses of LPS are rendered tolerantto subsequent exposure to LPS and manifest a profoundly altered response to LPS.Increasing evidence suggests that monocytic cells from patients with sepsis andseptic shock survivors have characteristics of LPS tolerance. Thus, anunderstanding of the molecular mechanisms underlying activation and deactivationof macrophages in response to LPS is important for the development oftherapeutics for septic shock and the treatment of septic shock survivors. Overthe past several years, significant progress has been made in identifying andcharacterizing several key molecules and signal pathways involved in theregulation of macrophage functions by LPS. In this paper, we summarize thecurrent findings of the functions of the LPS receptor complex, which is composedof CD14, Toll-like receptor 4 (TLR4), and myeloid differentiation protein-2(MD-2), and the signal pathways of this LPS receptor complex with regard to bothactivation and deactivation of macrophages by LPS. In addition, recenttherapeutic approaches for septic shock targeting the LPS receptor complex aredescribed.
PMID 14609719
Model Abstract

Entity

e1: e10: e11:LPS:LBP e12:CD14 e13:LPS:CD14 e14:LPS:TLR4:MD2:MYD88_dimer:MAL:IRAK1:IRAK4 e15:TLR4 e16:MD2 e17:TLR4:MD2 e18:LPS:TLR4:MD2 e19:LPS:TLR4:MD2:MYD88_dimer:MAL:IRAK1{p}:IRAK4 e2: e20:(MYD88)2 e21:LPS:TLR4:MD2:MYD88_dimer e22:IRAK1 e23:LPS:TLR4:MD2:MYD88_dimer:MAL e24:IKK-alpha e25:IRAK1{p} e26:IKK-beta e27:TRAF6 e28:IRAK1{p}:TRAF6 e29:MAPK e3: e30:MAPK{active} e31:AP-1 e32:AP-1{active} e33:IKK e34:IKK{active} e35:IkappaBalpha:NF-KappaB e36:IkappaBalpha{p}:NF-kappaB e37:IkappaB{ub}:NF-kappaB e38:protein remnants e39:NF-kappaB e4: e40:NF-kappaB e41:TNF-alpha e42:IkappaB e43:MAL e45:IRF3 e46:IRF3{p} e47:IRF3{p} e48:e48 e49:IRAK4 e5:LPS e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:LBP e60: e61: e62: e65:IRAK1{p}{ub}:TRAF6 e66:e66 e67:HSP90:HSP70:CXCR4:GDF5 e68:HSP90:HSP70:CXCR4:GDF5:LPS e69:peptidoglycan e7: e70:Nod1 e71:Peptidoglycan:Nod1 e72:RIP2 e73:Peptidoglycan:Nod1:RIP2 e74:IKK-gamma e75:RIP2:IKKgamma e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p25 p26 p27 p28 p29 p3 p32 p33 p34 p4 p5 p6 p7 p8 p9
Model Detail
148.92056729300177, 36.75091136622638
792.0888638834512, 1278.5346907110998

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
156.55228834518346, 56.29272209533167
767.7766676883938, 1200.643844930313

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
1103.5, 178.0
44.4600899850025, 54.44092651224796

LPS:LBP

--

e11

cso30:c:Complex

cso30:i:CC_Extracellular

--

p1

p2

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
894.5, 144.0
34.728919299657875, 56.317166431877645

CD14

--

e12

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
888.0, 229.0
48.033149171270715, 53.37016574585636

LPS:CD14

--

e13

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
893.0, 1025.0
39.352941176470594, 65.58823529411765

LPS:TLR4:MD2:MYD88_dimer:MAL:IRAK1:IRAK4

--

e14

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
894.5, 465.0
39.0, 60.0

TLR4

--

e15

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
915.0, 533.5
53.279999999999994, 39.959999999999994

MD2

--

e16

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
889.0, 588.0
47.98342541436464, 53.31491712707182

TLR4:MD2

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p4

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
893.5, 654.0
43.0, 60.0

LPS:TLR4:MD2

--

e18

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
888.0, 1167.0
39.352941176470594, 65.58823529411765

LPS:TLR4:MD2:MYD88_dimer:MAL:IRAK1{p}:IRAK4

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
148.92056729300177, 36.75091136622638
792.0888638834512, 1278.5346907110998

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
751.0, 667.5
51.845342706502635, 33.699472759226715

(MYD88)2

--

e20

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
896.0, 749.0
39.352941176470594, 65.58823529411765

LPS:TLR4:MD2:MYD88_dimer

--

e21

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
780.0, 1060.0
23.555659494855004, 54.35921421889616

IRAK1

--

e22

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p32

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
892.0, 875.0
39.352941176470594, 65.58823529411765

LPS:TLR4:MD2:MYD88_dimer:MAL

--

e23

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
241.0, 563.0
26.0, 60.0

IKK-alpha

--

e24

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
709.0, 146.0
54.5121951219512, 43.60975609756098

IRAK1{p}

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

p8

p9

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
316.0, 595.0
26.0, 60.0

IKK-beta

--

e26

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
490.5, 247.0
35.27993560072449, 57.21070637955323

TRAF6

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
584.0, 153.0
47.93370165745857, 53.2596685082873

IRAK1{p}:TRAF6

--

e28

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
231.0, 242.0
26.0, 60.0

MAPK

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p10

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
164.76234457067073, 54.36158203717825
760.4053093281132, 1243.3133493691973

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
319.0, 338.0
23.38540692235734, 53.96632366697848

MAPK{active}

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
194.0, 465.5
53.419199034010866, 32.94183940430671

AP-1

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p11

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
300.0, 548.5
54.75950895552425, 33.76836385590662

AP-1{active}

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

p11

--

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
410.5, 346.0
43.0, 60.0

IKK

--

e33

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
574.5, 350.0
43.0, 60.0

IKK{active}

--

e34

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
406.0, 457.5
51.23364862145301, 31.594083316562692

IkappaBalpha:NF-KappaB

--

e35

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p13

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
600.0, 457.0
47.5609756097561, 38.048780487804876

IkappaBalpha{p}:NF-kappaB

--

e36

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
422.0, 537.0
52.3372988103569, 40.12526242127362

IkappaB{ub}:NF-kappaB

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
553.0, 571.0
42.18265364732911, 40.77656519241815

protein remnants

--

e38

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p15

--

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
547.0, 639.5
49.663916280941834, 30.62608170658081

NF-kappaB

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
194.06963253435853, 85.18025571134365
701.790733400738, 1181.676002020865

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
546.0, 823.5
52.851680418595286, 32.591869591467095

NF-kappaB

--

e40

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
426.0, 924.0
60.0, 32.0

TNF-alpha

--

e41

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p17

--

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
590.0, 1000.0
60.0, 32.0

IkappaB

--

e42

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p18

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
743.0, 762.5
52.8646748681898, 34.36203866432338

MAL

--

e43

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p19

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
725.0, 895.5
53.41919903401086, 32.941839404306705

IRF3

--

e45

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p20

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
742.0, 1011.0
49.63414634146341, 39.70731707317074

IRF3{p}

--

e46

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
620.0731707317073, 1056.658536585366
47.9268292682927, 38.34146341463414

IRF3{p}

--

e47

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
490.0, 1140.0
60.0, 32.0

e48

--

e48

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p22

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
655.0, 742.0
26.0, 60.0

IRAK4

--

e49

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
1202.0, 91.0
60.0, 34.0

LPS

--

e5

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
316.58716616669085, 774.0803271577071
430.7529029829025, 434.26505253356504

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
363.11168827657593, 784.3717775806684
251.87413693972343, 420.88933222965636

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
322.2021946971942, 779.876472622734
419.52284592189613, 422.67276160351076

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
323.00434163012335, 780.7681873096612
417.9185520560378, 420.88933222965636

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
316.58716616669085, 774.0803271577071
430.7529029829025, 434.26505253356504

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
316.58716616669085, 774.0803271577071
430.7529029829025, 434.26505253356504

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
323.00434163012335, 780.7681873096612
417.9185520560378, 420.88933222965636

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
631.0287638748803, 952.4232645431547
26.911074604791484, 27.081821958238276

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
560.4398337771235, 1077.2633207129684
76.2039586282602, 76.68746307574253

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
316.58716616669085, 774.0803271577071
430.7529029829025, 434.26505253356504

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
974.0, 93.5
54.42141275910646, 33.55987120144899

LBP

--

e6

cso30:c:Protein

cso30:i:CC_Extracellular

--

p2

p1

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
418.11320172000137, 967.0641281419535
13.641311512562472, 7.301426322264414

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
417.6576797157518, 945.2895470477368
46.69100543558745, 93.42814446239524

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
437.24512589848644, 1006.0558198688076
7.28835206799413, 8.102169709476007

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
366.0, 156.0
52.883135059482164, 40.54373687893632

IRAK1{p}{ub}:TRAF6

--

e65

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
204.0, 161.0
40.287191269385396, 38.94428489373922

e66

--

e66

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p26

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
897.0, 310.0
45.1764705882353, 75.29411764705883

HSP90:HSP70:CXCR4:GDF5

--

e67

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
894.0, 402.0
36.0, 60.0

HSP90:HSP70:CXCR4:GDF5:LPS

--

e68

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
69.0, 1111.0
60.0, 34.0

peptidoglycan

--

e69

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p28

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
159.32745963688583, 41.89583603390862
776.7924012371308, 1223.598383267986

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
153.0, 1175.5
39.0, 60.0

Nod1

--

e70

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p28

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
162.0, 932.0
31.0, 60.0

Peptidoglycan:Nod1

--

e71

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
258.0, 807.5
50.062386798148516, 30.87180519219159

RIP2

--

e72

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p29

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
151.5, 751.0
43.0, 60.0

Peptidoglycan:Nod1:RIP2

--

e73

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
203.0, 610.0
26.0, 60.0

IKK-gamma

--

e74

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6 p7

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
345.5, 668.0
33.1511414764206, 40.593234460923185

RIP2:IKKgamma

--

e75

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
162.10263092858833, 63.49116512604312
745.1862065866579, 1202.8276871477894

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
169.50308770646149, 85.08649421817759
741.7840227933261, 1187.0529034321926

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
1113.0, 97.0
30.0, 30.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m6*m5*0.1

nodelay

--

true

0

false

--

Go back
317.0, 257.0
30.0, 30.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c21 : 1
stoichiometry:c30 : 1

m29*m28*0.1

nodelay

--

true

0

false

PMID: 14609719 TRAF6 activates MAPK kinases.

Go back
313.0, 465.0
30.0, 30.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c34 : 1
stoichiometry:c33 : 1

m31*m30*0.1

nodelay

--

true

0

false

PMID: 14609719 TRAF6 activates MAPK kinases,which can lead to AP-1 activation through MAPK.

Go back
493.0, 365.0
30.0, 30.0

p12

p12

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c22 : 1
stoichiometry:c85 : 1
stoichiometry:c36 : 1

m33*m28*m75*0.1

nodelay

--

true

0

false

PMID: 14609719 TRAF6 activates the inhibitors of ¦ÊB (I¦ÊB) kinase (IKK) complex.

Go back
497.0, 461.0
30.0, 30.0

p13

p13

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c40 : 1
stoichiometry:c39 : 1

m35*m34*0.1

nodelay

--

true

0

false

PMID: 14609719 The IKK complex is composed of 2 catalytic subunits IKK¦Á and IKK¦Â and one regulatory subunit IKK¦Ã and induces phosphorylation of I¦ÊB.

Go back
521.0, 529.0
30.0, 30.0

p14

p14

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1

m36*0.1

nodelay

--

true

0

false

PMID: 14609719 The phosphorylation of the I¦ÊBs results in their polyubiquitination, which in turn leads to their 26S proteasome-mediated degradation.

Go back
465.0, 621.0
30.0, 30.0

p15

p15

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c45 : 1

m37*0.1

nodelay

--

true

0

false

PMID: 14609719 The phosphorylation of the I¦ÊBs results in their polyubiquitination, which in turn leads to their 26S proteasome-mediated degradation.

Go back
557.0, 713.0
30.0, 30.0

p16

p16

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c47 : 1

m39*0.1

nodelay

--

true

0

false

PMID: 14609719 NF-¦ÊB translocates into the nucleus.

Go back
529.0, 933.0
30.0, 30.0

p17

p17

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c49 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 14609719 NF-¦ÊappaB translocate into the nucleus and activate the transcription of many ¦ÊB-dependent genes, including TNF-¦Á and I¦ÊB¦Á.

Go back
601.0, 944.0
27.0, 27.0

p18

p18

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1

m40*0.1

nodelay

--

true

0

false

PMID: 14609719 NF-¦ÊappaB translocate into the nucleus and activate the transcription of many ¦ÊB-dependent genes, including TNF-¦Á and I¦ÊB¦Á.

Go back
827.0, 764.0
30.0, 30.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c23 : 1
stoichiometry:c25 : 1

m43*m21*0.1

nodelay

--

true

0

false

PMID: 14609719 TIRAP/Mal binds directly to TLR4. PMID: 14609719,12447441 TIRAP-deficient mice have similar LPS-responsive phenotypes to MyD88-deficient mice with regard to the MyD88-independent pathway.

Go back
1001.0, 193.0
30.0, 30.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1
stoichiometry:c88 : 1

m11*m12*0.1

nodelay

--

true

0

false

--

Go back
797.0, 960.0
27.0, 27.0

p20

p20

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c57 : 1
stoichiometry:c56 : 1

m45*m18*0.1

nodelay

--

true

0

false

PMID: 14609719 Activation of TLR4 by LPS also induces the phosphorylation and nuclear translocation of IRF3.

Go back
721.0, 1113.0
30.0, 30.0

p21

p21

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c59 : 1

m46*0.1

nodelay

--

true

0

false

PMID: 14609719 Activation of TLR4 by LPS also induces the phosphorylation and nuclear translocation of IRF3.

Go back
505.0, 1061.0
30.0, 30.0

p22

p22

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1

m47*0.1

nodelay

--

true

0

false

PMID: 14609719 Activation of TLR4 by LPS induces the phosphorylation and nuclear translocation of IRF3, which causes up-regulation of a set of genes, including IFN-¦Â.

Go back
485.0, 161.0
30.0, 30.0

p25

p25

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 14609719 Phosphorylated IRAK-1 first binds TRAF6, resulting in the activation of NF-¦ÊB. The phosphorylated IRAK-1 is then degraded in an ubiquitination-dependent pathway.

Go back
289.0, 165.0
30.0, 30.0

p26

p26

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c71 : 1
stoichiometry:c72 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 14609719 Phosphorylated IRAK-1 first binds TRAF6, resulting in the activation of NF-¦ÊB. The phosphorylated IRAK-1 is then degraded in an ubiquitination-dependent pathway.

Go back
977.0, 313.0
30.0, 30.0

p27

p27

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c73 : 1
stoichiometry:c74 : 1
stoichiometry:c93 : 1

m13*m67*0.1

nodelay

--

true

0

false

PMID: 14609719 LBP transfers LPS to membrane CD14, and the intercalated LPS is released in lipid membrane; subsequently,the intercalated LPS binds to a complex of receptors composed of chemokine receptor 4, growth differentiation factor 5, and heat shock proteins 70 and 90 in lipid rafts.

Go back
163.0, 1037.0
30.0, 30.0

p28

p28

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c77 : 1
stoichiometry:c78 : 1

m69*m70*0.1

nodelay

--

true

0

false

PMID: 14609719, 12791997 Nod1 specifically detects a diaminopimelate-containing N-acetylglucosamine-N-acetylmuramic acid tripeptide motif of peptidoglycan found in Gram-negative bacteria.

Go back
165.0, 855.0
27.0, 27.0

p29

p29

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c79 : 1
stoichiometry:c80 : 1
stoichiometry:c81 : 1

m71*m72*0.1

nodelay

--

true

0

false

PMID: 14609719,11894097 Nod1 activates NF-¦ÊB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKK¦Ã, the regulatory subunit of the IKK complex.

Go back
993.0, 529.0
30.0, 30.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c8 : 1
stoichiometry:c10 : 1

m16*m15*0.1

nodelay

--

true

0

false

PMID: 14609719 MD-2, a small protein that lacks a transmembrane domain, is identified to associate with the extracellular domain of TLR4.

Go back
835.0, 987.0
30.0, 30.0

p4

p32

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c13 : 1
stoichiometry:c29 : 1
stoichiometry:c90 : 1

m22*m49*m23*0.1

nodelay

--

true

0

false

PMID: 14609719 Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.

Go back
821.0, 1114.0
30.0, 30.0

p33

p33

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c91 : 1
stoichiometry:c94 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 14609719 Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.

Go back
946.0, 1104.0
30.0, 30.0

p34

p34

cso30:i:ME_Autophosphorylation

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c95 : 1
stoichiometry:c96 : 1
stoichiometry:c55 : 1

m14*m19*0.1

nodelay

--

true

0

false

PMID: 14609719 Dimers of MyD88 bind IRAK-1and IRAK-4 bringing the respective domains in close association,resulting in the phosphorylation of IRAK-1 by IRAK-4, which may induce the kinase activity of IRAK-1 leading to its autophosphorylation.

Go back
1161.0, 621.0
30.0, 30.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c75 : 1
stoichiometry:c14 : 1
stoichiometry:c92 : 1

m17*m68*0.1

nodelay

--

true

0

false

PMID: 14609719 CD14 concentrates LPS and presents it to TLR4-MD-2. TLR4, MD-2 and CD11b/CD18 are recruited to the rafts, thereby triggering multiple signaling cascades (i.e., activation of NF-¦ÊB and MAPK).

Go back
826.0, 667.0
30.0, 30.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1

m18*m20*0.1

nodelay

--

true

0

false

PMID: 14609719 The TIR domain of MyD88 associates with the TIR domain of TLR and IL-1 receptor.

Go back
381.0, 575.0
30.0, 30.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c52 : 1
stoichiometry:c63 : 1
stoichiometry:c62 : 1

m24*m26*m74*0.1

nodelay

--

true

0

false

PMID: 1469719 The IKK complex is composed of 2 catalytic subunits IKKa and IKKb and one regulatory subunit IKKg and induces phosphorylation of IkappaB. PMID: 1469719,11894097 Nod1 activates NF-kB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKKg, the regulatory subunit of the IKK complex. Studies using Rip2-deficient cells have demonstrated that Rip2 is essential for the activation of NF-kB by Nod1 and Nod2.

Go back
361.0, 744.0
30.0, 30.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c65 : 1
stoichiometry:c66 : 1
stoichiometry:c67 : 1

m74*m73*0.1

nodelay

--

true

0

false

PMID: 1469719,11894097 Nod1 activates NF-kB through its association with the receptor-interacting protein 2 (Rip2), a CARD-containing serine/threonine kinase that directly interacts with IKKg, the regulatory subunit of the IKK complex. Studies using Rip2-deficient cells have demonstrated that Rip2 is essential for the activation of NF-kB by Nod1 and Nod2.

Go back
650.0, 537.0
30.0, 30.0

p8

p8

cso30:i:ME_Dissociation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c24 : 1
stoichiometry:c19 : 1
stoichiometry:c37 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 14609719 IRAKs are subsequently phosphorylated and are dissociated from the receptor complex. IRAKs associate receptor complex transiently.(Fig3)

Go back
593.0, 261.0
30.0, 30.0

p9

p9

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c27 : 1
stoichiometry:c28 : 1

m25*m27*0.1

nodelay

--

true

0

false

PMID: 14609719, 9625770, 8599092 IRAKs are subsequently phosphorylated and are dissociated from the receptor complex and interact with another adaptor molecule, TRAF6.

Go back
1028.0, 111.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
943.4, 555.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
936.0, 278.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
937.0, 617.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
681.0, 788.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
944.8692675450285, 639.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
863.9972313548228, 683.2104534567059

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
803.0, 682.3474977942104

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
852.0, 697.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
673.8089875327071, 574.4906334205524

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
665.0, 567.0

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1150.9954075771186, 109.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.0, 590.2104534567059

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
354.5894663844041, 188.0

c21

c21

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
519.5596737495483, 206.0

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
864.9973714472759, 780.2050608063404

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
668.0, 197.86730641710568

c24

c24

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
850.0, 794.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
629.1284133972473, 190.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
526.0, 276.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
608.0, 214.0

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
864.3743112075098, 938.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1127.1568325994756, 127.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
331.1568325994756, 287.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
257.0, 272.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
247.0, 480.12119821037015

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
327.14812275204815, 495.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
328.219095869855, 392.0

c34

c34

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
454.0, 377.0

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
523.0, 380.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
675.0, 567.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
457.0, 474.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
527.0, 476.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1038.996999249707, 206.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
530.3281261544709, 405.0

c40

c40

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
557.3217584095579, 495.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
481.91272142305456, 546.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
456.0, 577.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
495.0, 604.4779925266494

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
495.0, 639.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
572.0, 670.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
572.0, 743.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
550.0111869151599, 856.0

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
493.9656097279368, 942.740986951436

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
929.0, 178.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
578.0, 856.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
616.0, 971.0

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
342.0, 601.6505331807703

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
768.0, 928.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
796.0, 779.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
934.9936129624039, 1134.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
786.9656235549245, 987.0

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
818.6945702910888, 714.0

c57

c57

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
743.456022239382, 1051.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
674.9620548405717, 1093.9407857588142

c59

c59

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
943.2636750760037, 215.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
543.0, 1076.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
520.0, 1091.0

c61

c61

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
399.0, 413.89240993648673

c62

c62

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
229.0, 596.1306830355181

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
229.0, 650.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
195.0, 761.8624146143251

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
198.5733100838305, 774.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
367.56892908110547, 716.8446454055273

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
522.9966414776018, 177.2317867094957

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
427.0, 176.0

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
804.0, 1023.6177335302002

c7

c7

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
326.99276672546495, 177.0

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
252.0, 180.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
319.0, 187.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
942.0, 334.19776902317903

c73

c73

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
934.8915800086061, 343.0

c74

c74

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
930.0, 446.0

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
117.0, 1072.529781167739

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
174.0, 1074.99461868265

c77

c77

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
178.0, 1000.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
178.0, 889.99840047984

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
934.0, 505.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
199.32415563218427, 834.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
175.54419110509903, 818.9814695414523

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
371.0, 402.2228841505914

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1005.1984430354239, 134.90972403379814

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
968.0, 547.2639240088533

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
865.0, 1015.0

c90

c90

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
856.8623479330104, 1076.0

c91

c91

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
947.3223806457179, 378.9726262449685

c92

c92

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
929.6530903510587, 207.11722775292472

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
851.0, 1144.0

c94

c94

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
932.0, 1083.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
927.0, 1140.6564023547028

c96

c96

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back