Oscillations in I/O monotone systems under negative feedback

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-dimensional (in many interesting examples, just one-dimensional) model reduction. This robustness makes the technique useful in the analysis of molecular biological models in which there is large uncertainty regarding the values of kinetic and other parameters. However, verifying the conditions needed in order to apply the SGT is not always easy. This paper provides an approach to the verification of the needed properties, and illustrates the approach through an application to a classical model of circadian oscillations, as a nontrivial ``case study,'' and also provides a theorem in the converse direction of predicting oscillations when the SGT conditions fail.Comment: Related work can be retrieved from second author's websit

Multi-Stability in Monotone Input/Output 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.Comment: See http://www.math.rutgers.edu/~sontag for related work; to appear in Systems and Control Letter

Monotone Control Systems

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 cell's most important subsystems.Comment: See http://www.math.rutgers.edu/~sontag/ for related wor

Convergence speed of unsteady distributed consensus: decay estimate along the settling spanning-trees

Results for estimating the convergence rate of non-stationary distributed consensus algorithms are provided, on the basis of qualitative (mainly topological) as well as basic quantitative information (lower-bounds on the matrix entries). The results appear to be tight in a number of instances and are illustrated through simple as well as more sophisticated examples. The main idea is to follow propagation of information along certain spanning trees which arise in the communication graph.Comment: 27 pages, 5 figure

Combinatorial approaches to Hopf bifurcations in systems of interacting elements

We describe combinatorial approaches to the question of whether families of real matrices admit pairs of nonreal eigenvalues passing through the imaginary axis. When the matrices arise as Jacobian matrices in the study of dynamical systems, these conditions provide necessary conditions for Hopf bifurcations to occur in parameterised families of such systems. The techniques depend on the spectral properties of additive compound matrices: in particular, we associate with a product of matrices a signed, labelled digraph termed a DSR^[2] graph, which encodes information about the second additive compound of this product. A condition on the cycle structure of this digraph is shown to rule out the possibility of nonreal eigenvalues with positive real part. The techniques developed are applied to systems of interacting elements termed "interaction networks", of which networks of chemical reactions are a special case.Comment: A number of minor errors and typos corrected, and some results slightly improve