An Analysis of a Circadian Model Using The Small-Gain Approach to Monotone Systems

A system is invariant with respect to an input transformation if we can transform any dynamic input by this function and obtain the same output dynamics after adjusting the initial conditions appropriately. Often, the set of all such input transformations forms a Lie group, the most prominent examples being scale-invariant ($u\mapsto e^pu$, $p\in\mathbb{R}$) and translational-invariant ($u\mapsto pu$) systems, the latter comprising linear systems with transfer function zeros ...

A new Small-Gain Theorem is presented for general nonlinear control systems. The novelty of this research work is that vector Lyapunov functions and functionals are utilized to derive various input-to-output stability and input-to-state stability results. It is shown that the proposed approach recovers several recent results as special instances and is extendible to several important classes of control systems such as large-scale complex systems, nonlinear sampled-data system...

Monotone systems are dynamical systems whose solutions preserve a partial order in the initial condition for all positive times. It stands to reason that some systems may preserve a partial order only after some initial transient. These systems are usually called eventually monotone. While monotone systems have a characterization in terms of their vector fields (i.e. Kamke-Muller condition), eventually monotone systems have not been characterized in such an explicit manner. I...

This paper studies the graph-theoretic conditions for stability of positive monotone systems. Using concepts from input-to-state stability and network small-gain theory, we first establish necessary and sufficient conditions for the stability of linear positive systems described by Metzler matrices. Specifically, we derive two sets of stability conditions based on two forms of input-to-state stability gains for Metzler systems, namely max-interconnection gains and sum-interco...

This paper (parts I and II) provides an expository introduction to monotone and near-monotone dynamical systems associated to biochemical networks, those whose graphs are consistent or near-consistent. Many conclusions can be drawn from signed network structure, associated to purely stoichiometric information and ignoring fluxes. In particular, monotone systems respond in a predictable fashion to perturbations and have robust and ordered dynamical characteristics, making them...

This paper addresses the problem of giving conditions for transcriptional systems to be globally entrained to external periodic inputs. By using contraction theory, a powerful tool from dynamical systems theory, it is shown that certain systems driven by external periodic signals have the property that all solutions converge to a fixed limit cycle. General results are proved, and the properties are verified in the specific case of some models of transcriptional systems. The b...

Sensitivity analysis is a classical and fundamental tool to evaluate the role of a given parameter in a given system characteristic. Because the phase response curve is a fundamental input--output characteristic of oscillators, we developed a sensitivity analysis for oscillator models in the space of phase response curves. The proposed tool can be applied to high-dimensional oscillator models without facing the curse of dimensionality obstacle associated with numerical explor...

This paper presents a fundamental relation between Output Asymptotic Gains (OAG) and Input-to-Output Stability (IOS) gains for linear systems. For any Input-to-State Stable, strictly causal linear system the minimum OAG is equal to the minimum IOS-gain. Moreover, both quantities can be computed by solving a specific optimal control problem and by considering only periodic inputs. The result is valid for wide classes of linear systems (involving delay systems or systems descri...

Circadian clocks exhibit the robustness of period and plasticity of phase against environmental changes such as temperature and nutrient conditions. Thus far, however, it is unclear how both are simultaneously achieved. By investigating distinct models of circadian clocks, we demonstrate reci- procity between robustness and plasticity: higher robustness in the period implies higher plasticity in the phase, where changes in period and in phase follow a linear relationship with...

The hypothalamic pituitary adrenal (HPA) axis responds to physical and mental challenge to maintain homeostasis in part by controlling the body's cortisol level. Dysregulation of the HPA axis is implicated in numerous stress-related diseases. For a structured model of the HPA axis that includes the glucocorticoid receptor but does not take into account the system response delay, we analyze linear and non-linear stability of stationary solutions. For a second mathematical mode...