| Publications of Eduardo D. Sontag jointly with P. de Leenheer |
| Articles in journal or book chapters |
| New checkable criteria for persistence of chemical reaction networks are proposed, which extend and complement existing ones. The new results allow the consideration of reaction rates which are time-varying, thus incorporating the effects of external signals, and also relax the assumption of existence of global conservation laws, thus allowing for inflows (production) and outflows (degradation). For time-invariant networks parameter-dependent conditions for persistence of certain classes of networks are provided. As an illustration, two networks arising in the systems biology literature are analyzed, namely a hypoxia and an apoptosis network. |
| This paper derives new results for certain classes of chemical reaction networks, linking structural to dynamical properties. In particular, it investigates their monotonicity and convergence without making assumptions on the form of the kinetics (e.g., mass-action) of the dynamical equations involved, and relying only on stoichiometric constraints. The key idea is to find an alternative representation under which the resulting system is monotone. As a simple example, the paper shows that a phosphorylation/dephosphorylation process, which is involved in many signaling cascades, has a global stability property. |
| This paper studies monotone tridiagonal systems with negative feedback. These systems possess the Poincar{\'e}-Bendixson property, which implies that, if orbits are bounded, if there is a unique steady state and this unique equilibrium is asymptotically stable, and if one can rule out periodic orbits, then the steady state is globally asymptotically stable. Different approaches are discussed to rule out period orbits. One is based on direct linearization, while the other uses the theory of second additive compound matrices. Among the examples that will illustrate our main theoretical results is the classical Goldbeter model of circadian rhythms. |
| Certain mass-action kinetics models of biochemical reaction networks, although described by nonlinear differential equations, may be partially viewed as state-dependent linear time-varying systems, which in turn may be modeled by convex compact valued positive linear differential inclusions. A result is provided on asymptotic stability of such inclusions, and applied to biochemical reaction networks with inflows and outflows. Included is also a characterization of exponential stability of general homogeneous switched systems |
| Persistency is the property, for differential equations in Rn, that solutions starting in the positive orthant do not approach the boundary. For chemical reactions and population models, this translates into the non-extinction property: provided that every species is present at the start of the reaction, no species will tend to be eliminated in the course of the reaction. This paper provides checkable conditions for persistence of chemical species in reaction networks, using concepts and tools from Petri net theory, and verifies these conditions on various systems which arise in the modeling of cell signaling pathways. |
| We analyze certain chemical reaction networks and show that every solution converges to some steady state. The reaction kinetics are assumed to be monotone but otherwise arbitrary. When diffusion effects are taken into account, the conclusions remain unchanged. The main tools used in our analysis come from the theory of monotone dynamical systems. We review some of the features of this theory and provide a self-contained proof of a particular attractivity result which is used in proving our main result. |
| We provide an almost-global stability result for a particular chemostat model, in which crowding effects are taken into consideration. The model can be rewritten as a negative feedback interconnection of two monotone i/o systems with well-defined characteristics, which allows the use of a small-gain theorem for feedback interconnections of monotone systems. This leads to a sufficient condition for almost-global stability, and we show that coexistence occurs in this model if the crowding effects are large enough. |
| We study a single species in a chemostat, limited by two nutrients, and separate nutrient uptake from growth. For a broad class of uptake and growth functions it is proved that a nontrivial equilibrium may exist. Moreover, if it exists it is unique and globally stable, generalizing a previous result by Legovic and Cruzado. |
| This paper deals with an almost global attractivity result for Lotka-Volterra systems with predator-prey interactions. These systems can be written as (negative) feedback systems. The subsystems of the feedback loop are monotone control systems, possessing particular input-output properties. We use a small-gain theorem, adapted to a context of systems with multiple equilibrium points to obtain the desired almost global attractivity result. It provides sufficient conditions to rule out oscillatory or more complicated behavior which is often observed in predator-prey systems. |
| A small-gain theorem is presented for almost global stability of monotone control systems which are open-loop almost globally stable, when constant inputs are applied. The theorem assumes "negative feedback" interconnections. This typically destroys the monotonicity of the original flow and potentially destabilizes the resulting closed-loop system. |
| Conference articles |
| This is a very summarized version ofthe first part of the paper "Persistence results for chemical reaction networks with time-dependent kinetics and no global conservation laws". |
| Conference version of paper "Conditions for global stability of monotone tridiagonal systems with negative feedback" |
| This paper derives new results for certain classes of chemical reaction networks, linking structural to dynamical properties. In particular, it investigates their monotonicity and convergence without making assumptions on the structure (e.g., mass-action kinetics) of the dynamical equations involved, and relying only on stoichiometric constraints. The key idea is to find a suitable set of coordinates under which the resulting system is cooperative. As a simple example, the paper shows that a phosphorylation/dephosphorylation process, which is involved in many signaling cascades, has a global stability property. |
| Monotone systems are dynamical systems for which the flow preserves a partial order. Some applications will be briefly reviewed in this paper. Much of the appeal of the class of monotone systems stems from the fact that roughly, most solutions converge to the set of equilibria. However, this usually requires a stronger monotonicity property which is not always satisfied or easy to check in applications. Following work of J.F. Jiang, we show that monotonicity is enough to conclude global attractivity if there is a unique equilibrium and if the state space satisfies a particular condition. The proof given here is self-contained and does not require the use of any of the results from the theory of monotone systems. We will illustrate it on a class of chemical reaction networks with monotone, but otherwise arbitrary, reaction kinetics. |
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