Finite-Time Stability Analysis of Switched Genetic Regulatory Networks

This paper investigates the finite-time stability problem of switching genetic regulatory networks (GRNs) with interval time-varying delays and unbounded continuous distributed delays. Based on the piecewise Lyapunov-Krasovskii functional and the average dwell time method, some new finite-time stability criteria are obtained in the form of linear matrix inequalities (LMIs), which are easy to be confirmed by the Matlab toolbox. The finite-time stability is taken into account in switching genetic regulatory networks for the first time and the average dwell time of the switching signal is obtained. Two numerical examples are presented to illustrate the effectiveness of our results

Data based identification and prediction of nonlinear and complex dynamical systems

We thank Dr. R. Yang (formerly at ASU), Dr. R.-Q. Su (formerly at ASU), and Mr. Zhesi Shen for their contributions to a number of original papers on which this Review is partly based. This work was supported by ARO under Grant No. W911NF-14-1-0504. W.-X. Wang was also supported by NSFC under Grants No. 61573064 and No. 61074116, as well as by the Fundamental Research Funds for the Central Universities, Beijing Nova Programme.Peer reviewedPostprin

The stochastic behavior of a molecular switching circuit with feedback

Background: Using a statistical physics approach, we study the stochastic switching behavior of a model circuit of multisite phosphorylation and dephosphorylation with feedback. The circuit consists of a kinase and phosphatase acting on multiple sites of a substrate that, contingent on its modification state, catalyzes its own phosphorylation and, in a symmetric scenario, dephosphorylation. The symmetric case is viewed as a cartoon of conflicting feedback that could result from antagonistic pathways impinging on the state of a shared component. Results: Multisite phosphorylation is sufficient for bistable behavior under feedback even when catalysis is linear in substrate concentration, which is the case we consider. We compute the phase diagram, fluctuation spectrum and large-deviation properties related to switch memory within a statistical mechanics framework. Bistability occurs as either a first-order or second-order non-equilibrium phase transition, depending on the network symmetries and the ratio of phosphatase to kinase numbers. In the second-order case, the circuit never leaves the bistable regime upon increasing the number of substrate molecules at constant kinase to phosphatase ratio. Conclusions: The number of substrate molecules is a key parameter controlling both the onset of the bistable regime, fluctuation intensity, and the residence time in a switched state. The relevance of the concept of memory depends on the degree of switch symmetry, as memory presupposes information to be remembered, which is highest for equal residence times in the switched states. Reviewers: This article was reviewed by Artem Novozhilov (nominated by Eugene Koonin), Sergei Maslov, and Ned Wingreen.Comment: Version published in Biology Direct including reviewer comments and author responses, 28 pages, 7 figure

Global synchronization for discrete-time stochastic complex networks with randomly occurred nonlinearities and mixed time delays

Copyright [2010] IEEE. This material is posted here with permission of the IEEE. Such permission of the IEEE does not in any way imply IEEE endorsement of any of Brunel University's products or services. Internal or personal use of this material is permitted. However, permission to reprint/republish this material for advertising or promotional purposes or for creating new collective works for resale or redistribution must be obtained from the IEEE by writing to [email protected]. By choosing to view this document, you agree to all provisions of the copyright laws protecting it.In this paper, the problem of stochastic synchronization analysis is investigated for a new array of coupled discrete-time stochastic complex networks with randomly occurred nonlinearities (RONs) and time delays. The discrete-time complex networks under consideration are subject to: (1) stochastic nonlinearities that occur according to the Bernoulli distributed white noise sequences; (2) stochastic disturbances that enter the coupling term, the delayed coupling term as well as the overall network; and (3) time delays that include both the discrete and distributed ones. Note that the newly introduced RONs and the multiple stochastic disturbances can better reflect the dynamical behaviors of coupled complex networks whose information transmission process is affected by a noisy environment (e.g., Internet-based control systems). By constructing a novel Lyapunov-like matrix functional, the idea of delay fractioning is applied to deal with the addressed synchronization analysis problem. By employing a combination of the linear matrix inequality (LMI) techniques, the free-weighting matrix method and stochastic analysis theories, several delay-dependent sufficient conditions are obtained which ensure the asymptotic synchronization in the mean square sense for the discrete-time stochastic complex networks with time delays. The criteria derived are characterized in terms of LMIs whose solution can be solved by utilizing the standard numerical software. A simulation example is presented to show the effectiveness and applicability of the proposed results

Super-transient scaling in time-delay autonomous Boolean network motifs

Autonomous Boolean networks are commonly used to model the dynamics of gene regulatory networks and allow for the prediction of stable dynamical attractors. However, most models do not account for time delays along the network links and noise, which are crucial features of real biological systems. Concentrating on two paradigmatic motifs, the toggle switch and the repressilator, we develop an experimental testbed that explicitly includes both inter-node time delays and noise using digital logic elements on field-programmable gate arrays. We observe transients that last millions to billions of characteristic time scales and scale exponentially with the amount of time delays between nodes, a phenomenon known as super-transient scaling. We develop a hybrid model that includes time delays along network links and allows for stochastic variation in the delays. Using this model, we explain the observed super-transient scaling of both motifs and recreate the experi- mentally measured transient distributions

Hopf bifurcation in a gene regulatory network model: Molecular movement causes oscillations

Gene regulatory networks, i.e. DNA segments in a cell which interact with each other indirectly through their RNA and protein products, lie at the heart of many important intracellular signal transduction processes. In this paper we analyse a mathematical model of a canonical gene regulatory network consisting of a single negative feedback loop between a protein and its mRNA (e.g. the Hes1 transcription factor system). The model consists of two partial differential equations describing the spatio-temporal interactions between the protein and its mRNA in a 1-dimensional domain. Such intracellular negative feedback systems are known to exhibit oscillatory behaviour and this is the case for our model, shown initially via computational simulations. In order to investigate this behaviour more deeply, we next solve our system using Greens functions and then undertake a linearized stability analysis of the steady states of the model. Our results show that the diffusion coefficient of the protein/mRNA acts as a bifurcation parameter and gives rise to a Hopf bifurcation. This shows that the spatial movement of the mRNA and protein molecules alone is sufficient to cause the oscillations. This has implications for transcription factors such as p53, NF-$kappa$B and heat shock proteins which are involved in regulating important cellular processes such as inflammation, meiosis, apoptosis and the heat shock response, and are linked to diseases such as arthritis and cancer