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a) Simplified network diagram showing the positive feedback loop for AKT activation with PI3K serving as an input. b) MatCont <t>bifurcation</t> analysis showing the stable (solid lines) and unstable (dashed lines) steady-state solutions for each downstream species in the model shown in (a) for different levels of PI3K input. While there is no bifurcation for PDK1, the other three species in the network (AKT, mTOR, and mTORC2) exhibit a limit point bifurcation (LP), indicated by a star, detected at a level of PI3K = 0.27083. c) Simplified network diagram showing an activator and inhibitor pair interacting via an AND gate to activate PI3K. d) Surface plot showing the steady-state activation level of PI3K for different levels of an upstream activator and inhibitor pair. The threshold for saturation of the downstream species in the positive feedback loop is shown as a grid. Increasing the level of inhibitor prevents PI3K from crossing this threshold.
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a) Simplified network diagram showing the positive feedback loop for AKT activation with PI3K serving as an input. b) MatCont bifurcation analysis showing the stable (solid lines) and unstable (dashed lines) steady-state solutions for each downstream species in the model shown in (a) for different levels of PI3K input. While there is no bifurcation for PDK1, the other three species in the network (AKT, mTOR, and mTORC2) exhibit a limit point bifurcation (LP), indicated by a star, detected at a level of PI3K = 0.27083. c) Simplified network diagram showing an activator and inhibitor pair interacting via an AND gate to activate PI3K. d) Surface plot showing the steady-state activation level of PI3K for different levels of an upstream activator and inhibitor pair. The threshold for saturation of the downstream species in the positive feedback loop is shown as a grid. Increasing the level of inhibitor prevents PI3K from crossing this threshold.

Journal: PLoS Computational Biology

Article Title: Roles of mTOR in thoracic aortopathy understood by complex intracellular signaling interactions

doi: 10.1371/journal.pcbi.1009683

Figure Lengend Snippet: a) Simplified network diagram showing the positive feedback loop for AKT activation with PI3K serving as an input. b) MatCont bifurcation analysis showing the stable (solid lines) and unstable (dashed lines) steady-state solutions for each downstream species in the model shown in (a) for different levels of PI3K input. While there is no bifurcation for PDK1, the other three species in the network (AKT, mTOR, and mTORC2) exhibit a limit point bifurcation (LP), indicated by a star, detected at a level of PI3K = 0.27083. c) Simplified network diagram showing an activator and inhibitor pair interacting via an AND gate to activate PI3K. d) Surface plot showing the steady-state activation level of PI3K for different levels of an upstream activator and inhibitor pair. The threshold for saturation of the downstream species in the positive feedback loop is shown as a grid. Increasing the level of inhibitor prevents PI3K from crossing this threshold.

Article Snippet: We performed numerical continuation and bifurcation analyses using the open-source software MatCont ( https://sourceforge.net/projects/matcont/ , [ ]) through MATLAB.

Techniques: Activation Assay