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Koo2013 Integrated Shear-Stress Induced NO Production Lab

About lab

Koo2013 Integrated Shear-Stress Induced NO Production Lab

This lab wraps the integrated Koo et al. (2013) endothelial mechanotransduction model from BioModels source BIOMD0000000468. The canvas model is named koo2013_integrated_shear_stress_no_production, matching the screenshots below, and connects a shear-stress stimulus surrogate through calcium handling, mechanosensor signalling, eNOS activation, and nitric oxide production. The models/core package handles SBML execution and numeric outputs, while models/visualisation owns internal grouped charts and narrative logic.

Use this lab when the question is the end-to-end NO-production response rather than the isolated calcium-influx or NO-production submodules.

Results Preview

The default published run spans 600 s and renders 10 visualization panels. The first view shows the canvas wiring beside the mechanical-input and calcium-subsystem plots. stimulus_intensity acts as the practical shear-stress input by driving IP3 production, while the calcium panel tracks extracellular, stored, cytosolic, buffered, IP3, and calmodulin-related pools.

Koo2013 integrated mechanical inputs and calcium results

The mid-run results expose the upstream signalling cascade. The mechanosensor panel follows FAK, Src, Shc, Ras, and adapter complexes, while the adjacent PI3K/AKT panel shows the downstream kinase axis that links mechanical stimulation to eNOS regulation.

Koo2013 integrated mechanosensor and PI3K results

The later panels focus on vasoactive output and negative regulation. Nitric oxide accumulates across the 600 s run as the active eNOS complex converts L-arginine, while PP2A and PTEN provide the regulatory phosphatase context.

Koo2013 integrated nitric oxide and phosphatase results

The summary view reports 65 species observables, identifies stored calcium in the ER lumen as the largest excursion, and notes that 26 of 65 observables settled within 1% over the final 10% of the run.

Koo2013 integrated summary diagnostics

Model Files

PathPurpose
lab.yamlLab title, IO wiring, runtime defaults, and canvas metadata.
models/core/model.yamlCore SBML execution package metadata, parameters, inputs, outputs, and units.
models/core/src/koo2013_integrated_shear_stress_no_production.pyTellurium-backed SBML execution wrapper.
models/core/data/BIOMD0000000468.xmlCurated SBML model file from BioModels.
models/visualisation/Internal presentation model for charts and narrative logic.
models/*/tests/Smoke coverage for core execution and visualisation behavior.

Inputs and Outputs

Inputs:

  • stimulus_intensity (1/s): IP3-production rate constant k1; the model's practical shear-stress stimulus surrogate.
  • integration_step (s): Tellurium output sampling interval.

Outputs:

  • active_eNOS: active eNOS-CaM-Ca4 complex amount, averaged over the wrapper's headline window.
  • cytosolic_calcium: cytosolic calcium amount, averaged over the wrapper's headline window.
  • nitric_oxide: nitric oxide amount, averaged over the wrapper's headline window.
  • state: latest values for the tracked named species.
  • summary: final, peak, minimum, and excursion diagnostics for the run.

Notes

The upstream SBML Shear Stress species is decorative in this wrapper; use stimulus_intensity for perturbation experiments. The state output carries 65 named species after filtering mass-balance placeholders from the 79-species SBML model.

Koo et al. (2013) integrated endothelial mechanotransduction model combining shear-stress sensing, calcium influx, eNOS activation, and NO production into a single ODE system.

Runtime

Duration600
Comms Step10

Runs

Total3
Completed3
Failed0

Metadata

Packagekoo2013-integrated-shear-stress-induced-no-production-lab
Created2026-05-04
Updated2026-05-14
biomechanicsendothelialshear-stressnitric-oxidemechanotransductionsbmlbiomodels_ebifaithfulvisualisationkoo2013

Manifest

{
  "io": {
    "inputs": [
      {
        "name": "integration_step",
        "maps_to": "koo2013_integrated_shear_stress_no_production.integration_step"
      },
      {
        "name": "stimulus_intensity",
        "maps_to": "koo2013_integrated_shear_stress_no_production.stimulus_intensity"
      }
    ],
    "outputs": [
      {
        "name": "active_eNOS",
        "maps_to": "koo2013_integrated_shear_stress_no_production.active_eNOS"
      },
      {
        "name": "cytosolic_calcium",
        "maps_to": "koo2013_integrated_shear_stress_no_production.cytosolic_calcium"
      },
      {
        "name": "nitric_oxide",
        "maps_to": "koo2013_integrated_shear_stress_no_production.nitric_oxide"
      },
      {
        "name": "state",
        "maps_to": "koo2013_integrated_shear_stress_no_production.state"
      },
      {
        "name": "summary",
        "maps_to": "koo2013_integrated_shear_stress_no_production.summary"
      }
    ]
  },
  "title": "Koo2013 Integrated Shear-Stress Induced NO Production Lab",
  "models": [
    {
      "path": "owned/models/koo2013_integrated_shear_stress_no_production",
      "alias": "koo2013_integrated_shear_stress_no_production",
      "parameters": {
        "model_path": "data/BIOMD0000000468.xml",
        "integration_step": 1
      },
      "provenance": {
        "owned_path": "owned/models/koo2013_integrated_shear_stress_no_production"
      }
    },
    {
      "path": "owned/models/visualisation",
      "alias": "visualisation",
      "provenance": {
        "owned_path": "owned/models/visualisation"
      }
    }
  ],
  "wiring": [
    {
      "to": [
        "visualisation.koo2013_integrated_shear_stress_no_production_active_eNOS"
      ],
      "from": "koo2013_integrated_shear_stress_no_production.active_eNOS"
    },
    {
      "to": [
        "visualisation.koo2013_integrated_shear_stress_no_production_cytosolic_calcium"
      ],
      "from": "koo2013_integrated_shear_stress_no_production.cytosolic_calcium"
    },
    {
      "to": [
        "visualisation.koo2013_integrated_shear_stress_no_production_nitric_oxide"
      ],
      "from": "koo2013_integrated_shear_stress_no_production.nitric_oxide"
    },
    {
      "to": [
        "visualisation.koo2013_integrated_shear_stress_no_production_state"
      ],
      "from": "koo2013_integrated_shear_stress_no_production.state"
    },
    {
      "to": [
        "visualisation.koo2013_integrated_shear_stress_no_production_summary"
      ],
      "from": "koo2013_integrated_shear_stress_no_production.summary"
    }
  ],
  "runtime": {
    "duration": 600,
    "initial_inputs": {},
    "communication_step": 10
  },
  "description": "Koo et al. (2013) integrated endothelial mechanotransduction model combining shear-stress sensing, calcium influx, eNOS activation, and NO production into a single ODE system.",
  "schema_version": "2.0"
}

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JSON
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  "dependency_policy_enabled": true,
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  "model_resolutions": [
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      "commit_sha": null,
      "model_id": "/Volumes/dem-ssd/imp/projects/Nitoons/Biosimulant/models/models-biomechanics/labs/koo2013-integrated/model",
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            "title": "Koo2013 Integrated Shear-Stress Induced NO Production - Mechanosensor cascade (FAK / Src / Shc / Ras / adapters)",
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          "description": "How does the focal-adhesion kinase pathway transduce mechanical shear into the upstream signalling cascade?",
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          "description": "How does shear-stimulated PI3K activate AKT through PI3P and PDK kinases?",
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            "title": "Koo2013 Integrated Shear-Stress Induced NO Production - eNOS activation chain (eNOS · CaM · Ca₄ · Hsp90 complexes)",
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          "description": "How does the eNOS enzyme assemble with calmodulin, calcium, and Hsp90 into its active complex?",
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                  [
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                  ],
                  [
                    571,
                    0.1
                  ],
                  [
                    572,
                    0.1
                  ],
                  [
                    573,
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                  ],
                  [
                    574,
                    0.1
                  ],
                  [
                    575,
                    0.1
                  ],
                  [
                    576,
                    0.1
                  ],
                  [
                    577,
                    0.1
                  ],
                  [
                    578,
                    0.1
                  ],
                  [
                    579,
                    0.1
                  ],
                  [
                    580,
                    0.1
                  ],
                  [
                    581,
                    0.1
                  ],
                  [
                    582,
                    0.1
                  ],
                  [
                    583,
                    0.1
                  ],
                  [
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                    0.1
                  ],
                  [
                    585,
                    0.1
                  ],
                  [
                    586,
                    0.1
                  ],
                  [
                    587,
                    0.1
                  ],
                  [
                    588,
                    0.1
                  ],
                  [
                    589,
                    0.1
                  ],
                  [
                    590,
                    0.1
                  ],
                  [
                    591,
                    0.1
                  ],
                  [
                    592,
                    0.1
                  ],
                  [
                    593,
                    0.1
                  ],
                  [
                    594,
                    0.1
                  ],
                  [
                    595,
                    0.1
                  ],
                  [
                    596,
                    0.1
                  ],
                  [
                    597,
                    0.1
                  ],
                  [
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                    0.1
                  ],
                  [
                    599,
                    0.1
                  ],
                  [
                    600,
                    0.1
                  ]
                ]
              }
            ],
            "title": "Koo2013 Integrated Shear-Stress Induced NO Production - Regulatory phosphatases (PP2A, PTEN)",
            "x_unit": "s"
          },
          "description": "How do the deactivating phosphatases respond as the upstream cascade ramps up?",
          "render": "timeseries"
        },
        {
          "data": {
            "categories": [
              "Stored calcium (ER lumen)",
              "Nitric oxide (NO)",
              "Buffered calcium (protein-bound)",
              "Calmodulin",
              "Calmodulin·Ca₂ complex",
              "Cytosolic calcium (Ca²⁺)",
              "Simulation time",
              "Pre-step time (model internal)"
            ],
            "title": "Koo2013 Integrated Shear-Stress Induced NO Production - largest excursions during the run",
            "values": [
              2410710.5761722727,
              111163.34172571372,
              28486.56722288728,
              2233.981911794388,
              2022.4568125430092,
              1001.3256294683874,
              600,
              600
            ]
          },
          "description": "Which observables shifted the most during the run?",
          "render": "bar"
        },
        {
          "data": {
            "columns": [
              "Question",
              "Answer"
            ],
            "rows": [
              [
                "What did this run track?",
                "65 species observables in the Koo2013 Integrated Shear-Stress Induced NO Production SBML model"
              ],
              [
                "How long did it run?",
                "600 s"
              ],
              [
                "Which observable changed the most?",
                "Stored calcium (ER lumen) (-2.41e+06)"
              ],
              [
                "Largest peak?",
                "Stored calcium (ER lumen) at 2.83e+06 substance"
              ],
              [
                "Did anything reach steady state?",
                "26 of 65 observables settled within 1% over the last 10% of the run."
              ]
            ],
            "title": "What Happened"
          },
          "description": "What did this simulation actually show, in plain language?",
          "render": "table"
        }
      ]
    }
  ]
}