| Publications about 'feedback control' |
| Articles in journal or book chapters |
| Recent work on data-driven control and reinforcement learning has renewed interest in a relatively old field in control theory: model-free optimal control approaches which work directly with a cost function and do not rely upon perfect knowledge of a system model. Instead, an "oracle" returns an estimate of the cost associated to, for example, a proposed linear feedback law to solve a linear-quadratic regulator problem. This estimate, and an estimate of the gradient of the cost, might be obtained by performing experiments on the physical system being controlled. This motivates in turn the analysis of steepest descent algorithms and their associated gradient differential equations. This paper studies the effect of errors in the estimation of the gradient, framed in the language of input to state stability, where the input represents a perturbation from the true gradient. Since one needs to study systems evolving on proper open subsets of Euclidean space, a self-contained review of input to state stability definitions and theorems for systems that evolve on such sets is included. The results are then applied to the study of noisy gradient systems, as well as the associated steepest descent algorithms. |
| Cells respond to biochemical and physical internal as well as external signals. These signals can be broadly classified into two categories: (a) ``actionable'' or ``reference'' inputs that should elicit appropriate biological or physical responses such as gene expression or motility, and (b) ``disturbances'' or ``perturbations'' that should be ignored or actively filtered-out. These disturbances might be exogenous, such as binding of nonspecific ligands, or endogenous, such as variations in enzyme concentrations or gene copy numbers. In this context, the term robustness describes the capability to produce appropriate responses to reference inputs while at the same time being insensitive to disturbances. These two objectives often conflict with each other and require delicate design trade-offs. Indeed, natural biological systems use complicated and still poorly understood control strategies in order to finely balance the goals of responsiveness and robustness. A better understanding of such natural strategies remains an important scientific goal in itself and will play a role in the construction of synthetic circuits for therapeutic and biosensing applications. A prototype problem in robustly responding to inputs is that of ``robust tracking'', defined by the requirement that some designated internal quantity (for example, the level of expression of a reporter protein) should faithfully follow an input signal while being insensitive to an appropriate class of perturbations. Control theory predicts that a certain type of motif, called integral feedback, will help achieve this goal, and this motif is, in fact, a necessary feature of any system that exhibits robust tracking. Indeed, integral feedback has always been a key component of electrical and mechanical control systems, at least since the 18th century when James Watt employed the centrifugal governor to regulate steam engines. Motivated by this knowledge, biological engineers have proposed various designs for biomolecular integral feedback control mechanisms. However, practical and quantitatively predictable implementations have proved challenging, in part due to the difficulty in obtaining accurate models of transcription, translation, and resource competition in living cells, and the stochasticity inherent in cellular reactions. These challenges prevent first-principles rational design and parameter optimization. In this work, we exploit the versatility of an Escherichia coli cell-free transcription-translation (TXTL) to accurately design, model and then build, a synthetic biomolecular integral controller that precisely controls the expression of a target gene. To our knowledge, this is the first design of a functioning gene network that achieves the goal of making gene expression track an externally imposed reference level, achieves this goal even in the presence of disturbances, and whose performance quantitatively agrees with mathematical predictions. |
| During normal kidney function, there are are routinely wide swings in proximal tubule fluid flow and proportional changes in Na+ reabsorption across tubule epithelial cells. This "glomerulotubular balance" occurs in the absence of any substantial change in cell volume, and is thus a challenge to coordinate luminal membrane solute entry with peritubular membrane solute exit. In this work, linear optimal control theory is applied to generate a configuration of regulated transporters that could achieve this result. A previously developed model of rat proximal tubule epithelium is linearized about a physiologic reference condition; the approximate linear system is recast as a dynamical system; and a Riccati equation is solved to yield optimal linear feedback that stabilizes Na+ flux, cell volume, and cell pH. This optimal feedback control is largely consigned to three physiologic variables, cell volume, cell electrical potential, and lateral intercellular hydrostatic pressure. Transport modulation by cell volume stabilizes cell volume; transport modulation by electrical potential or interspace pressure act to stabilize Na+ flux and cell pH. This feedback control is utilized in a tracking problem, in which reabsorptive Na+ flux varies over a factor of two. The resulting control parameters consist of two terms, an autonomous term and a feedback term, and both terms include transporters on both luminal and peritubular cell membranes. Overall, the increase in Na+ flux is achieved with upregulation of luminal Na+/H+ exchange and Na+-glucose cotransport, with increased peritubular Na+-3HCO_3- and K+-Cl- cotransport, and with increased Na+,K+-ATPase activity. The configuration of activated transporters emerges as testable hypothesis of the molecular basis for glomerulotubular balance. It is suggested that the autonomous control component at each cell membrane could represent the cytoskeletal effects of luminal flow. |
| 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 paper provides a precise result which shows that insensitivity to small measurement errors in closed-loop stabilization can be attained provided that the feedback controller ignores observations during small time intervals. |
| We deal with the question of obtaining explicit feedback control laws that stabilize a nonlinear system, under the assumption that a "control Lyapunov function" is known. In previous work, the case of unbounded controls was considered. Here we obtain results for bounded and/or positive controls. We also provide some simple preliminary remarks regarding a set stability version of the problem and a version for systems subject to disturbances. |
| This paper proposes an approach to the problem of establishing the existence of observers for deterministic dynamical systems. This approach differs from the standard one based on Luenberger observers in that the observation error is not required to be Markovian given the past input and output data. A general abstract result is given, which special- izes to new results for parametrized families of linear systems, delay systems and other classes of systems. Related problems of feedback control and regulation are also studied. |
| Conference articles |
| Motivated by the current interest in using Artificial intelligence (AI) tools in control design, this paper takes the first steps towards bridging results from gradient methods for solving the LQR control problem, and neural networks. More specifically, it looks into the case where one wants to find a Linear Feed-Forward Neural Network (LFFNN) that minimizes the Linear Quadratic Regulator (LQR) cost. This work develops gradient formulas that can be used to implement the training of LFFNNs to solve the LQR problem, and derives an important conservation law of the system. This conservation law is then leveraged to prove global convergence of solutions and invariance of the set of stabilizing networks under the training dynamics. These theoretical results are then followed by and extensive analysis of the simplest version of the problem (the ``scalar case'') and by numerical evidence of faster convergence of the training of general LFFNNs when compared to traditional direct gradient methods. These results not only serve as indication of the theoretical value of studying such a problem, but also of the practical value of LFFNNs as design tools for data-driven control applications. |
| Systems theory can play an important in unveiling fundamental limitations of learning algorithms and architectures when used to control a dynamical system, and in suggesting strategies for overcoming these limitations. As an example, a feedforward neural network cannot stabilize a double integrator using output feedback. Similarly, a recurrent NN with differentiable activation functions that stabilizes a non-strongly stabilizable system must be itself open loop unstable, a fact that has profound implications for training with noisy, finite data. A potential solution to this problem, motivated by results on stabilization with periodic control, is the use of neural nets with periodic resets, showing that indeed systems theoretic analysis is instrumental in developing architectures capable of controlling certain classes of unstable systems. This short conference paper also argues that when the goal is to learn control oriented models, the loss function should reflect closed loop, rather than open loop model performance, a fact that can be accomplished by using gap-metric motivated loss functions. |
| 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. |
| Cellular reprogramming is traditionally accomplished through an open loop control approach, wherein key transcription factors are injected in cells to steer a gene regulatory network toward a pluripotent state. Recently, a closed loop feedback control strategy was proposed in order to achieve more accurate control. Previous analyses of the controller were based on deterministic models, ignoring the substantial stochasticity in these networks, Here we analyze the Chemical Master Equation for reaction models with and without the feedback controller. We computationally and analytically investigate the performance of the controller in biologically relevant parameter regimes where stochastic effects dictate system dynamics. Our results indicate that the feedback control approach still ensures reprogramming even when analyzed using a stochastic model. |
| Internal reports |
| Since its introduction by Briat, Gupta and Khammash, the antithetic feedback controller design has attracted considerable attention in both theoretical and experimental systems biology. The case in which the plant is a two-dimensional linear system (making the closed-loop system a nonlinear four-dimensional system) has been analyzed in much detail. This system has a unique equilibrium but, depending on parameters, it may exhibit periodic orbits. This note shows that, for any parameter choices, every bounded trajectory satisfies a Poincare'-Bendixson property: the dynamics in the omega-limit set of any precompact solution is conjugate to the dynamics in a compact invariant subset of a two-dimensional Lipschitz dynamical system, thus precluding chaotic and other strange attractors. |
| This note analyzes incoherent feedforward loops in signal processing and control. It studies the response properties of IFFL's to exponentially growing inputs, both for a standard version of the IFFL and for a variation in which the output variable has a positive self-feedback term. It also considers a negative feedback configuration, using such a device as a controller. It uncovers a somewhat surprising phenomenon in which stabilization is only possible in disconnected regions of parameter space, as the controlled system's growth rate is varied. |
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