| Publications about 'global stability' |
| Articles in journal or book chapters |
| Synthetic constructs in biotechnology, bio-computing, and proposed gene therapy interventions are often based on plasmids or transfected circuits which implement some form of on-off (toggle or flip-flop) switch. For example, the expression of a protein used for therapeutic purposes might be triggered by the recognition of a specific combination of inducers (e.g., antigens), and memory of this event should be maintained across a cell population until a specific stimulus commands a coordinated shut-off. The robustness of such a design is hampered by molecular (intrinsic) or environmental (extrinsic) noise, which may lead to spontaneous changes of state in a subset of the population and is reflected in the bimodality of protein expression, as measured for example using flow cytometry. In this context, a majority-vote correction circuit, which brings deviant cells back into the required state, is highly desirable. To address this concrete challenge, we have developed a new theoretical design for quorum-sensing (QS) synthetic toggles. QS provides a way for cells to broadcast their states to the population as a whole so as to facilitate consensus. Our design is endowed with strong theoretical guarantees, based on monotone dynamical systems theory, of global stability and no oscillations, and which leads to robust consensus states. |
| 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. |
| A class of distributed systems with a cyclic interconnection structure is considered. These systems arise in several biochemical applications and they can undergo diffusion driven instability which leads to a formation of spatially heterogeneous patterns. In this paper, a class of cyclic systems in which addition of diffusion does not have a destabilizing effect is identified. For these systems global stability results hold if the "secant" criterion is satisfied. In the linear case, it is shown that the secant condition is necessary and sufficient for the existence of a decoupled quadratic Lyapunov function, which extends a recent diagonal stability result to partial differential equations. For reaction-diffusion equations with nondecreasing coupling nonlinearities global asymptotic stability of the origin is established. All of the derived results remain true for both linear and nonlinear positive diffusion terms. Similar results are shown for compartmental systems. |
| This paper considers a class of systems with a cyclic structure that arises, among other examples, in dynamic models for certain biochemical reactions. We first show that a criterion for local stability, derived earlier in the literature, is in fact a necessary and sufficient condition for diagonal stability of the corresponding class of matrices. We then revisit a recent generalization of this criterion to output strictly passive systems, and recover the same stability condition using our diagonal stability result as a tool for constructing a Lyapunov function. Using this procedure for Lyapunov construction we exhibit classes of cyclic systems with sector nonlinearities and characterize their global stability properties. |
| 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. |
| 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. |
| We present two constructions of controllers that globally stabilize linear systems subject to control saturation. We allow essentially arbitrary saturation functions. The only conditions imposed on the system are the obvious necessary ones, namely that no eigenvalues of the uncontrolled system have positive real part and that the standard stabilizability rank condition hold. One of the constructions is in terms of a "neural-network type" one-hidden layer architecture, while the other one is in terms of cascades of linear maps and saturations. |
| Conference articles |
| Integral feedback can help achieve robust tracking independently of external disturbances. Motivated by this knowledge, biological engineers have proposed various designs of biomolecular integral feedback controllers to regulate biological processes. In this paper, we theoretically analyze the operation of a particular synthetic biomolecular integral controller, which we have recently proposed and implemented experimentally. Using a combination of methods, ranging from linearized analysis to sum-of-squares (SOS) Lyapunov functions, we demonstrate that, when the controller is operated in closed-loop, it is capable of providing integral corrections to the concentration of an output species in such a manner that the output tracks a reference signal linearly over a large dynamic range. We investigate the output dependency on the reaction parameters through sensitivity analysis, and quantify performance using control theory metrics to characterize response properties, thus providing clear selection guidelines for practical applications. We then demonstrate the stable operation of the closed-loop control system by constructing quartic Lyapunov functions using SOS optimization techniques, and establish global stability for a unique equilibrium. Our analysis suggests that by incorporating effective molecular sequestration, a biomolecular closed-loop integral controller that is capable of robustly regulating gene expression is feasible. |
| Conference version of paper "Conditions for global stability of monotone tridiagonal systems with negative feedback" |
| For distributed systems with a cyclic interconnection structure, a global stability result is shown to hold if the secant criterion is satisfied. |
| 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. |
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