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

Oscillatory behavior is a key property of many biological systems. The Small-Gain Theorem (SGT) for input/output monotone systems provides a sufficient condition for global asymptotic stability of an equilibrium and hence its violation is a necessary condition for the existence of periodic solutions. One advantage of the use of the monotone SGT technique is its robustness with respect to all perturbations that preserve monotonicity and stability properties of a very low-dimen...

Monotone systems constitute one of the most important classes of dynamical systems used in mathematical biology modeling. The objective of this paper is to extend the notion of monotonicity to systems with inputs and outputs, a necessary first step in trying to understand interconnections, especially including feedback loops, built up out of monotone components. Basic definitions and theorems are provided, as well as an application to the study of a model of one of the ce...

Monotone systems constitute one of the most important classes of dynamical systems used in mathematical biology modeling. The objective of this paper is to extend the notion of monotonicity to systems with inputs and outputs, a necessary first step in trying to understand interconnections, especially including feedback loops, built up out of monotone components. Basic definitions and theorems are provided, as well as an application of a theorem regarding negative feedback loo...

Quasi steady state assumptions are often used to simplify complex systems of ordinary differential equations in modelling of biochemical processes. The simplified system is designed to have the same qualitative properties as the original system and to have a small number of variables. This enables to use the stability and bifurcation analysis to reveal a deeper structure in the dynamics of the original system. This contribution shows that introducing delays to quasi steady st...

This note remarks that small-gain results for a negative feedback loop around a monotone system can be seen as consequences of results concerning an extended monotone system.

We provide a new global small-gain theorem for feedback interconnections of monotone input-output systems with multi-valued input-state characteristics. This extends a recent small-gain theorem of Angeli and Sontag for monotone systems with singleton-valued characteristics. We prove our theorem using Thieme's convergence theory for asymptotically autonomous systems. An illustrative example is also provided.

This note introduces a new notion of random dynamical system with inputs and outputs, and sketches a small-gain theorem for monotone systems which generalizes a similar theorem known for deterministic systems.

This paper studies the emergence of multi-stability and hysteresis in those systems that arise, under positive feedback, starting from monotone systems with well-defined steady-state responses. Such feedback configurations appear routinely in several fields of application, and especially in biology. Characterizations of global stability behavior are stated in terms of easily checkable graphical conditions. An example of a signaling cascade under positive feedback is presented...

We prove the global asymptotic stability of a well-known delayed negative-feedback model of testosterone dynamics, which has been proposed as a model of oscillatory behavior. We establish stability (and hence the impossibility of oscillations) even in the presence of delays of arbitrary length.

We extend the setup in our previous paper to deal with the case in which more than one steady state may exist in feedback configurations. This provides a foundation for the analysis of multi-stability and hysteresis behaviour in high dimensional feedback systems.