Publications about 'nonlinear systems' |
Articles in journal or book chapters |
In biological processes such as embryonic development, hematopoietic cell differentiation, and the arising of tumor heterogeneity and consequent resistance to therapy, mechanisms of gene activation and deactivation may play a role in the emergence of phenotypically heterogeneous yet genetically identical (clonal) cellular populations. Mathematically, the variability in phenotypes in the absence of genetic variation can be modeled through the existence of multiple metastable attractors in nonlinear systems subject with stochastic switching, each one of them associated to an alternative epigenetic state. An important theoretical and practical question is that of estimating the number and location of these states, as well as their relative probabilities of occurrence. This paper focuses on a rigorous analytic characterization of multiple modes under slow promoter kinetics, which is a feature of epigenetic regulation. It characterizes the stationary distributions of Chemical Master Equations for gene regulatory networks as a mixture of Poisson distributions. As illustrations, the theory is used to tease out the role of cooperative binding in stochastic models in comparison to deterministic models, and applications are given to various model systems, such as toggle switches in isolation or in communicating populations and a trans-differentiation network. |
Resistance to chemotherapy is a major impediment to the successful treatment of cancer. Classically, resistance has been thought to arise primarily through random genetic mutations, after which mutated cells expand via Darwinian selection. However, recent experimental evidence suggests that the progression to resistance need not occur randomly, but instead may be induced by the therapeutic agent itself.This process of resistance induction can be a result of genetic changes, or can occur through epigenetic alterations that cause otherwise drug-sensitive cancer cells to undergo ``phenotype switching''. This relatively novel notion of resistance further complicates the already challenging task of designing treatment protocols that minimize the risk of evolving resistance. In an effort to better understand treatment resistance, we have developed a mathematical modeling framework that incorporates both random and drug-induced resistance. Our model demonstrates that the ability (or lack thereof) of a drug to induce resistance can result in qualitatively different responses to the same drug dose and delivery schedule. The importance of induced resistance in treatment response led us to ask if, in our model, one can determine the resistance induction rate of a drug for a given treatment protocol. Not only could we prove that the induction parameter in our model is theoretically identifiable, we have also proposed a possible in vitro experiment which could practically be used to determine a treatment's propensity to induce resistance. |
We consider a nonlinear SISO system that is a cascade of a scalar "bottleneck entrance" with a stable positive linear system. In response to any periodic inflow, all solutions converge to a unique periodic solution with the same period. We study the problem of maximizing the averaged throughput via controlled switching. We compare two strategies: 1) switching between a high and low value, and 2 ~using a constant inflow equal to the prescribed mean value. We show that no possible switching policy can outperform a constant inflow rate, though it can approach it asymptotically. We describe several potential applications of this problem in traffic systems, ribosome flow models, and scheduling at security checks. |
This paper introduces two generalizations of systems invariant with respect to continuous sets of input transformations, that is, systems whose output dynamics remain invariant when applying a transformation to the input and simultaneously adjusting the initial conditions. These generalizations concern systems invariant with respect to time-dependent input transformations with exponentially increasing or decreasing ``strength'', and systems invariant with respect to transformations of the "nonlinear derivatives" of the input. Interestingly, these two generalizations of invariant systems encompass linear time-invariant (LTI) systems with real transfer function zeros of arbitrary multiplicity. Furthermore, the zero-dynamics of systems possessing our generalized invariances show properties analogous to those of LTI systems with transfer function zeros, generalizing concepts like pole-zero cancellation, the rejection of ramps by Hurwitz LTI systems with a zero at the origin with multiplicity two, and (to a certain extend) the superposition principle with respect to inputs zeroing the output. |
Contraction theory is a powerful tool for proving asymptotic properties of nonlinear dynamical systems including convergence to an attractor and entrainment to a periodic excitation. We introduce three new forms of generalized contraction (GC) that are motivated by allowing contraction to take place after small transients in time and/or amplitude. These forms of GC are useful for several reasons. First, allowing small transients does not destroy the asymptotic properties provided by standard contraction. Second, in some cases as we change the parameters in a contractive system it becomes a GC just before it looses contractivity. In this respect, GC is the analogue of marginal stability in Lyapunov stability theory. We provide checkable sufficient conditions for GC, and demonstrate their usefulness using several models from systems biology that are not contractive, with respect to any norm, yet are GC. |
We develop and analyze a general model for large-scale simultaneous mRNA translation and competition for ribosomes. Such models are especially important when dealing with highly expressed genes, as these consume more resources. For our model, we prove that the compound system always converges to a steady-state and that it always entrains or phase locks to periodically time-varying transition rates in any of the mRNA molecules. We use this model to explore the interactions between the various mRNA molecules and ribosomes at steady-state. We show that increasing the length of an mRNA molecule decreases the production rate of all the mRNAs. Increasing any of the codon translation rates in a specific mRNA molecule yields a local effect: an increase in the translation rate of this mRNA, and also a global effect: the translation rates in the other mRNA molecules all increase or all decrease. These results suggest that the effect of codon decoding rates of endogenous and heterologous mRNAs on protein production might be more complicated than previously thought. |
Contraction theory provides an elegant way to analyze the behavior of certain nonlinear dynamical systems. In this paper, we discuss the application of contraction to synchronization of diffusively interconnected components described by nonlinear differential equations. We provide estimates of convergence of the difference in states between components, in the cases of line, complete, and star graphs, and Cartesian products of such graphs. We base our approach on contraction theory, using matrix measures derived from norms that are not induced by inner products. Such norms are the most appropriate in many applications, but proofs cannot rely upon Lyapunov-like linear matrix inequalities, and different techniques, such as the use of the Perron-Frobenious Theorem in the cases of L1 or L-infinity norms, must be introduced. |
A recent biological study has demonstrated that the gene expression pattern entrains to a periodically varying abundance of tRNA molecules. This motivates developing mathematical tools for analyzing entrainment of translation elongation to intra-cellular signals such as tRNAs levels and other factors affecting translation. We consider a recent deterministic mathematical model for translation called the Ribosome Flow Model (RFM). We analyze this model under the assumption that the elongation rate of the tRNA genes and/or the initiation rate are periodic functions with a common period T. We show that the protein synthesis pattern indeed converges to a unique periodic trajectory with period T. The analysis is based on introducing a novel property of dynamical systems, called contraction after a short transient (CAST), that may be of independent interest. We provide a sufficient condition for CAST and use it to prove that the RFM is CAST, and that this implies entrainment. Our results support the conjecture that periodic oscillations in tRNA levels and other factors related to the translation process can induce periodic oscillations in protein levels, and suggest a new approach for engineering genes to obtain a desired, periodic, synthesis rate. |
This paper provides synchronization conditions for networks of nonlinear systems, where each component of the network itself consists of subsystems represented as operators in the extended L2 space. The synchronization conditions are provided by combining the input-output properties of the subsystems with information about the structure of network. The paper also explores results for state-space models as well as biochemical applications. The work is motivated by cellular networks where signaling occurs both internally, through interactions of species, and externally, through intercellular signaling. |
This paper presents a stability test for a class of interconnected nonlinear systems motivated by biochemical reaction networks. One of the main results determines global asymptotic stability of the network from the diagonal stability of a "dissipativity matrix" which incorporates information about the passivity properties of the subsystems, the interconnection structure of the network, and the signs of the interconnection terms. This stability test encompasses the "secant criterion" for cyclic networks presented in our previous paper, and extends it to a general interconnection structure represented by a graph. A second main result allows one to accommodate state products. This extension makes the new stability criterion applicable to a broader class of models, even in the case of cyclic systems. The new stability test is illustrated on a mitogen activated protein kinase (MAPK) cascade model, and on a branched interconnection structure motivated by metabolic networks. Finally, another result addresses the robustness of stability in the presence of diffusion terms in a compartmental system made out of identical systems. |
This expository presentation, prepared for a summer course, addresses the precise formulation of questions of robustness with respect to disturbances, using the paradigm of input to state stability. It provides an intuitive and informal presentation of the main concepts. |
A commonly employed measure of the signal amplification properties of an input/output system is its induced L2 norm, sometimes also known as H-infinity gain. In general, however, it is extremely difficult to compute the numerical value for this norm, or even to check that it is finite, unless the system being studied is linear. This paper describes a class of systems for which it is possible to reduce this computation to that of finding the norm of an associated linear system. In contrast to linearization approaches, a precise value, not an estimate, is obtained for the full nonlinear model. The class of systems that we study arose from the modeling of certain biological intracellular signaling cascades, but the results should be of wider applicability. |
This paper proposes several definitions of observability for nonlinear systems and explores relationships among them. These observability properties involve the existence of a bound on the norm of the state in terms of the norms of the output and the input on some time interval. A Lyapunov-like sufficient condition for observability is also obtained. As an application, we prove several variants of LaSalle's stability theorem for switched nonlinear systems. These results are demonstrated to be useful for control design in the presence of switching as well as for developing stability results of Popov type for switched feedback systems. |
We discuss several issues related to the stabilizability of nonlinear systems. First, for continuously stabilizable systems, we review constructions of feedbacks that render the system input-to-state stable with respect to actuator errors. Then, we discuss a recent paper which provides a new feedback design that makes globally asymptotically controllable systems input-to-state stable to actuator errors and small observation noise. We illustrate our constructions using the nonholonomic integrator, and discuss a related feedback design for systems with disturbances. |
A new notion of input-to-state stability involving infinity norms of input derivatives up to a finite order k is introduced and characterized. An example shows that this notion of stability is indeed weaker than the usual ISS. Applications to the study of global asymptotic stability of cascaded nonlinear systems are discussed. |
We consider a new Lyapunov-type characterization of detectability for nonlinear systems without controls, in terms of lower-semicontinuous (not necessarily smooth, or even continuous) dissipation functions, and prove its equivalence to the GASMO (global asymptotic stability modulo outputs) and UOSS (uniform output-to-state stability) properties studied in previous work. The result is then extended to provide a construction of a discontinuous dissipation function characterization of the IOSS (input-to-state stability) property for systems with controls. This paper complements a recent result on smooth Lyapunov characterizations of IOSS. The utility of non-smooth Lyapunov characterizations is illustrated by application to a well-known transistor network example. |
This paper introduces and studies a new definition of the minimum-phase property for general smooth nonlinear control systems. The definition does not rely on a particular choice of coordinates in which the system takes a normal form or on the computation of zero dynamics. In the spirit of the ``input-to-state stability'' philosophy, it requires the state and the input of the system to be bounded by a suitable function of the output and derivatives of the output, modulo a decaying term depending on initial conditions. The class of minimum-phase systems thus defined includes all affine systems in global normal form whose internal dynamics are input-to-state stable and also all left-invertible linear systems whose transmission zeros have negative real parts. As an application, we explain how the new concept enables one to develop a natural extension to nonlinear systems of a basic result from linear adaptive control. |
We study nonlinear systems with both control and disturbance inputs. The main problem addressed in the paper is design of state feedback control laws that render the closed-loop system integral-input-to-state stable (iISS) with respect to the disturbances. We introduce an appropriate concept of control Lyapunov function (iISS-CLF), whose existence leads to an explicit construction of such a control law. The same method applies to the problem of input-to-state stabilization. Converse results and techniques for generating iISS-CLFs are also discussed. |
This work explores Lyapunov characterizations of the input-output-to-state stability (IOSS) property for nonlinear systems. The notion of IOSS is a natural generalization of the standard zero-detectability property used in the linear case. The main contribution of this work is to establish a complete equivalence between the input-output-to-state stability property and the existence of a certain type of smooth Lyapunov function. As corollaries, one shows the existence of "norm-estimators", and obtains characterizations of nonlinear detectability in terms of relative stability and of finite-energy estimates. |
This paper deals with the theory of structure, stability, robustness, and stabilization for an appealing class of nonlinear systems which arises in the analysis of chemical networks. The results given here extend, but are also heavily based upon, certain previous work by Feinberg, Horn, and Jackson, of which a self-contained and streamlined exposition is included. The theoretical conclusions are illustrated through an application to the kinetic proofreading model proposed by McKeithan for T-cell receptor signal transduction. |
One of the fundamental facts in control theory (Artstein's theorem) is the equivalence, for systems affine in controls, between continuous feedback stabilizability to an equilibrium and the existence of smooth control Lyapunov functions. This equivalence breaks down for general nonlinear systems, not affine in controls. One of the main results in this paper establishes that the existence of smooth Lyapunov functions implies the existence of (in general, discontinuous) feedback stabilizers which are insensitive to small errors in state measurements. Conversely, it is shown that the existence of such stabilizers in turn implies the existence of smooth control Lyapunov functions. Moreover, it is established that, for general nonlinear control systems under persistently acting disturbances, the existence of smooth Lyapunov functions is equivalent to the existence of (possibly) discontinuous) feedback stabilizers which are robust with respect to small measurement errors and small additive external disturbances. |
We provide an explicit KL stability or input-to-state stability (ISS) estimate for a sampled-data nonlinear system in terms of the KL estimate for the corresponding discrete-time system and a K function describing inter-sample growth. It is quite obvious that a uniform inter-sample growth condition, plus an ISS property for the exact discrete-time model of a closed-loop system, implies uniform ISS of the sampled-data nonlinear system; our results serve to quantify these facts by means of comparison functions. Our results can be used as an alternative to prove and extend results of Aeyels et al and extend some results by Chen et al to a class of nonlinear systems. Finally, the formulas we establish can be used as a tool for some other problems which we indicate. |
This note discusses two integral variants of the input-to-state stability (ISS) property, which represent nonlinear generalizations of L2 stability, in much the same way that ISS generalizes L-infinity stability. Both variants are equivalent to ISS for linear systems. For general nonlinear systems, it is shown that one of the new properties is strictly weaker than ISS, while the other one is equivalent to it. For bilinear systems, a complete characterization is provided of the weaker property. An interesting fact about functions of type KL is proved as well. |
The notion of input-to-state stability (ISS) has proved to be useful in nonlinear systems analysis. This paper discusses a dual notion, output-to-state stability (OSS). A characterization is provided in terms of a dissipation inequality involving storage (Lyapunov) functions. Combining ISS and OSS there results the notion of input/output-to-state stability (IOSS), which is also studied and related to the notion of detectability, the existence of observers, and output injection. |
This paper deals with the orders of input/output equations satisfied by nonlinear systems. Such equations represent differential (or difference, in the discrete-time case) relations between high-order derivatives (or shifts, respectively) of input and output signals. It is shown that, under analyticity assumptions, there cannot exist equations of order less than the minimal dimension of any observable realization; this generalizes the known situation in the classical linear case. The results depend on new facts, themselves of considerable interest in control theory, regarding universal inputs for observability in the discrete case, and observation spaces in both the discrete and continuous cases. Included in the paper is also a new and simple self-contained proof of Sussmann's universal input theorem for continuous-time analytic systems. |
Controllability questions for discrete-time nonlinear systems are addressed in this paper. In particular, we continue the search for conditions under which the group-like notion of transitivity implies the stronger and semigroup-like property of forward accessibility. We show that this implication holds, pointwise, for states which have a weak Poisson stability property, and globally, if there exists a global "attractor" for the system. |
A basic open question for discrete-time nonlinear systems is that of determining when, in analogy with the classical continuous-time "positive form of Chow's Lemma", accessibility follows from transitivity of a natural group action. This paper studies the problem, and establishes the desired implication for analytic systems in several cases: (i) compact state space, (ii) under a Poisson stability condition, and (iii) in a generic sense. In addition, the paper studies accessibility properties of the "control sets" recently introduced in the context of dynamical systems studies. Finally, various examples and counterexamples are provided relating the various Lie algebras introduced in past work. |
It is shown that realizability of an input/output operators by a finite-dimensional continuous-time rational control system is equivalent to the existence of a high-order algebraic differential equation satisfied by the corresponding input/output pairs ("behavior"). This generalizes, to nonlinear systems, the classical equivalence between autoregressive representations and finite dimensional linear realizability. |
This paper studies fundamental analytic properties of generating series for nonlinear control systems, and of the operators they define. It then applies the results obtained to the extension of facts, which relate realizability and algebraic input/output equations, to local realizability and analytic equations. |
The notion of controllability was identified by Kalman as one of the central properties determining system behavior. His simple rank condition is ubiquitous in linear systems analysis. This article presents an elementary and expository overview of the generalizations of this test to a condition for testing accessibility of discrete and continuous time nonlinear systems. |
This paper surveys some well-known facts as well as some recent developments on the topic of stabilization of nonlinear systems. (NOTE: figures are not included in file; they were pasted-in.) |
This paper presents a geometric study of controllability for discrete-time nonlinear systems. Various accessibility properties are characterized in terms of Lie algebras of vector fields. Some of the results obtained are parallel to analogous ones in continuous-time, but in many respects the theory is substantially different and many new phenomena appear. |
This paper concerns itself with the existence of open-loop control generators for nonlinear (continuous-time) systems. The main result is that, under relatively mild assumptions on the original system, and for each fixed compact subset of the state space, there always exists one such generator. This is a new system with the property that the controls it produces are sufficiently rich to preserve complete controllability along nonsingular trajectories. General results are also given on the continuity and differentiability of the input to state mapping for various p-norms on controls, as well as a comparison of various nonlinear controllability notions. |
We continue here our investigation into the preservation of structural properties under the sampling of nonlinear systems. The main new result is that, under minimal hypothesis, a controllable system always satisfies a strong type of approximate sampled controllability. |
This paper was a conference version of the SIAM paper that introduced the idea of control-Lyapunov functions for arbitrary nonlinear systems. (The journal paper was submitted in 1981 but only published in 1983.) |
A state-space realization theory is presented for a wide class of discrete time input/output behaviors. Although In many ways restricted, this class does include as particular cases those treated in the literature (linear, multilinear, internally bilinear, homogeneous), as well ss certain nonanalytic nonlinearities. The theory is conceptually simple, and matrix-theoretic algorithms are straightforward. Finite-realizability of these behaviors by state-affine systems is shown to be equivalent both to the existence of high-order input/output equadons and to realizability by more general types of systems. |
Conference articles |
This is a tutorial paper on control-theoretic methods for the analysis of biological systems. |
This tutorial paper deals with the Internal Model Principle (IMP) from different perspectives. The goal is to start from the principle as introduced and commonly used in the control theory and then enlarge the vision to other fields where "internal models" play a role. The biology and neuroscience fields are specifically targeted in the paper. The paper ends by presenting an "abstract" theory of IMP applicable to a large class of systems. |
In this article, we show that scale-invariant systems, as well as systems invariant with respect to other input transformations, can realize nonlinear differential operators: when excited by inputs obeying functional forms characteristic for a given class of invariant systems, the systems' outputs converge to constant values directly quantifying the speed of the input. |
Contraction theory provides an elegant way to analyze the behaviors of certain nonlinear dynamical systems. Under sometimes easy to check hypotheses, systems can be shown to have the incremental stability property that trajectories converge to each other. The present paper provides a self-contained introduction to some of the basic concepts and results in contraction theory, discusses applications to synchronization and to reaction-diffusion partial differential equations, and poses several open questions. |
This conference paper presented a version of an approximate internal model principle, for linear systems. A subsequent paper at the IFAC 2008 conference improved on this result by extending it to a class of nonlinear systems. |
For systems whose output is to be kept small (thought of as an error output), the notion of input to output stability (IOS) arises. Alternatively, when considering a system whose output is meant to provide information about the state (i.e. a measurement output), one arrives at the detectability notion of output to state stability (OSS). Combining these concepts, one may consider a system with two types of outputs, an error and a measurement. This leads naturally to a notion of partial detectability which we call measurement to error stability (MES). This property characterizes systems in which the error signal is detectable through the measurement signal. This paper provides a partial Lyapunov characterization of the MES property. A closely related property of stability in three measures (SIT) is introduced, which characterizes systems for which the error decays whenever it dominates the measurement. The SIT property is shown to imply MES, and the two are shown to be equivalent under an additional boundedness assumption. A nonsmooth Lyapunov characterization of the SIT property is provided, which yields the partial characterization of MES. The analysis is carried out on systems described by differential inclusions -- implicitly incorporating a disturbance input with compact value-set. |
This paper studies the input-to-state stability (ISS) property for discrete-time nonlinear systems. We show that many standard ISS results may be extended to the discrete-time case. More precisely, we provide a Lyapunov-like sufficient condition for ISS, and we show the equivalence between the ISS property and various other properties, as well as provide a small gain theorem. |
Contains a proof of a technical step, which was omitted from the journal paper due to space constraints |
We suggest that a very natural mathematical framework for the study of dissipation -in the sense of Willems, Moylan and Hill, and others- is that of indefinite quasimetric spaces. Several basic facts about dissipative systems are seen to be simple consequences of the properties of such spaces. Quasimetric spaces provide also one natural context for optimal control problems, and even for "gap" formulations of robustness. |
Invited talk at the 1994 ICM. Paper deals with the notion of observables for nonlinear systems, and their role in realization theory, minimality, and several control and path planning questions. |
This paper studies various types of input/output representations for nonlinear continuous time systems. The algebraic and analytic i/o equations studied in previous papers by the authors are generalized to integral and integro-differential equations, and an abstract notion is also considered. New results are given on generic observability, and these results are then applied to give conditions under which that the minimal order of an equation equals the minimal possible dimension of a realization, just as with linear systems but in contrast to the discrete time nonlinear theory. |
Coprime right fraction representations are obtained for nonlinear systems defined by differential equations, under assumptions of stabilizability and detectability. A result is also given on left (not necessarily coprime) factorizations. |
This paper studies time-optimal control questions for a certain class of nonlinear systems. This class includes a large number of mechanical systems, in particular, rigid robotic manipulators with torque constraints. As nonlinear systems, these systems have many properties that are false for generic systems of the same dimensions. |
Internal reports |
This paper continues the study of a model which was introduced in earlier work by the authors to study spontaneous and induced evolution to drug resistance under chemotherapy. The model is fit to existing experimental data, and is then validated on additional data that had not been used when fitting. In addition, an optimal control problem is studied numerically. |
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