Dataset Information

A flexible and qualitatively stable model for cell cycle dynamics including DNA damage effects.

ABSTRACT: This paper includes a conceptual framework for cell cycle modeling into which the experimenter can map observed data and evaluate mechanisms of cell cycle control. The basic model exhibits qualitative stability, meaning that regardless of magnitudes of system parameters its instances are guaranteed to be stable in the sense that all feasible trajectories converge to a certain trajectory. Qualitative stability can also be described by the signs of real parts of eigenvalues of the system matrix. On the biological side, the resulting model can be tuned to approximate experimental data pertaining to human fibroblast cell lines treated with ionizing radiation, with or without disabled DNA damage checkpoints. Together these properties validate a fundamental, first order systems view of cell dynamics. Classification Codes: 15A68.

SUBMITTER: Jeffries CD

PROVIDER: S-EPMC3329186 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

A flexible and qualitatively stable model for cell cycle dynamics including DNA damage effects.

Jeffries Clark D CD Johnson Charles R CR Zhou Tong T Simpson Dennis A DA Kaufmann William K WK

Gene regulation and systems biology 20120411

This paper includes a conceptual framework for cell cycle modeling into which the experimenter can map observed data and evaluate mechanisms of cell cycle control. The basic model exhibits qualitative stability, meaning that regardless of magnitudes of system parameters its instances are guaranteed to be stable in the sense that all feasible trajectories converge to a certain trajectory. Qualitative stability can also be described by the signs of real parts of eigenvalues of the system matrix. O ...[more]

PMID: 22553421

Similar Datasets

Project description:Stability of human gait is the ability to maintain upright posture during walking against external perturbations. It is a complex process determined by a number of cross-related factors, including gait trajectory, joint impedance and neural control strategies. Here, we consider a control strategy that can achieve stable steady-state periodic gait while maintaining joint flexibility with the lowest possible joint impedance. To this end, we carried out a simulation study of a heel-toe footed biped model with hip, knee and ankle joints and a heavy head-arms-trunk element, working in the sagittal plane. For simplicity, the model assumes a periodic desired joint angle trajectory and joint torques generated by a set of feed-forward and proportional-derivative feedback controllers, whereby the joint impedance is parametrized by the feedback gains. We could show that a desired steady-state gait accompanied by the desired joint angle trajectory can be established as a stable limit cycle (LC) for the feedback controller with an appropriate set of large feedback gains. Moreover, as the feedback gains are decreased for lowering the joint stiffness, stability of the LC is lost only in a few dimensions, while leaving the remaining large number of dimensions quite stable: this means that the LC becomes saddle-type, with a low-dimensional unstable manifold and a high-dimensional stable manifold. Remarkably, the unstable manifold remains of low dimensionality even when the feedback gains are decreased far below the instability point. We then developed an intermittent neural feedback controller that is activated only for short periods of time at an optimal phase of each gait stride. We characterized the robustness of this design by showing that it can better stabilize the unstable LC with small feedback gains, leading to a flexible gait, and in particular we demonstrated that such an intermittent controller performs better if it drives the state point to the stable manifold, rather than directly to the LC. The proposed intermittent control strategy might have a high affinity for the inverted pendulum analogy of biped gait, providing a dynamic view of how the step-to-step transition from one pendular stance to the next can be achieved stably in a robust manner by a well-timed neural intervention that exploits the stable modes embedded in the unstable dynamics.

Dataset Information

A flexible and qualitatively stable model for cell cycle dynamics including DNA damage effects.

Publications

A flexible and qualitatively stable model for cell cycle dynamics including DNA damage effects.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets