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Like engineering systems, biological systems must also operate effectively in the presence of internal and external uncertainty—such as genetic mutations or temperature changes, for example. It is not surprising, then, that evolution has resulted in the widespread use of feedback, and research in systems biology over the past decade has shown that feedback control systems are widely found in biology. As an increasing number of researchers in the life sciences become interested in control-theoretic ideas such as feedback, stability, noise and disturbance attenuation, and robustness, there is a need for a text that explains feedback control as it applies to biological systems. Written by established researchers in both control engineering and systems biology, Feedback Control in Systems Biology explains how feedback control concepts can be applied to systems biology. Filling the need for a text on control theory for systems biologists, it provides an overview of relevant ideas and methods from control engineering and illustrates their application to the analysis of biological systems with case studies in cellular and molecular biology. Control Theory for Systems Biologists The book focuses on the fundamental concepts used to analyze the effects of feedback in biological control systems, rather than the control system design methods that form the core of most control textbooks. In addition, the authors do not assume that readers are familiar with control theory. They focus on "control applications" such as metabolic and gene-regulatory networks rather than aircraft, robots, or engines, and on mathematical models derived from classical reaction kinetics rather than classical mechanics. Another significant feature of the book is that it discusses nonlinear systems, an understanding of which is crucial for systems biologists because of the highly nonlinear nature of biological systems. The authors cover tools and techniques for the analysis of linear and nonlinear systems; negative and positive feedback; robustness analysis methods; techniques for the reverse-engineering of biological interaction networks; and the analysis of stochastic biological control systems. They also identify new research directions for control theory inspired by the dynamic characteristics of biological systems. A valuable reference for researchers, this text offers a sound starting point for scientists entering this fascinating and rapidly developing field.
A survey of how engineering techniques from control and systems theory can be used to help biologists understand the behavior of cellular systems.
Clearly explaining the logical analysis of biological control phenomena, Biological Feedback answers questions concerning everything from regulation to logic. This rare monograph presents a formal methodology for analyzing the dynamic behavior of complex systems. The easy-to-read text describes a simple logical formalization called "kinetic logic". The reader discovers how this method is used to predict all possible patterns of behavior of which a system is capable. It includes specific conditions required for each pattern. It also explains how to modify an incorrect model in order to account for the observed behavior. The authors give special attention to the two basic types of simple feedback loops: positive and negative. This volume is filled with easy-to-use tables, providing quick reference throughout the book. The subject matter is of great interest to everyone working in molecular genetics and developmental biology. Researchers, immunologists, physical chemists, physicists, electrical engineers, economists, and mathematicians will find this unique text to be an informative, indispensable resource.
This book provides an accessible introduction to the principles and tools for modeling, analyzing, and synthesizing biomolecular systems. It begins with modeling tools such as reaction-rate equations, reduced-order models, stochastic models, and specific models of important core processes. It then describes in detail the control and dynamical systems tools used to analyze these models. These include tools for analyzing stability of equilibria, limit cycles, robustness, and parameter uncertainty. Modeling and analysis techniques are then applied to design examples from both natural systems and synthetic biomolecular circuits. In addition, this comprehensive book addresses the problem of modular composition of synthetic circuits, the tools for analyzing the extent of modularity, and the design techniques for ensuring modular behavior. It also looks at design trade-offs, focusing on perturbations due to noise and competition for shared cellular resources. Featuring numerous exercises and illustrations throughout, Biomolecular Feedback Systems is the ideal textbook for advanced undergraduates and graduate students. For researchers, it can also serve as a self-contained reference on the feedback control techniques that can be applied to biomolecular systems. Provides a user-friendly introduction to essential concepts, tools, and applications Covers the most commonly used modeling methods Addresses the modular design problem for biomolecular systems Uses design examples from both natural systems and synthetic circuits Solutions manual (available only to professors at press.princeton.edu) An online illustration package is available to professors at press.princeton.edu
This textbook contains the essential knowledge in modeling, simulation, analysis, and applications in dealing with biological cellular control systems. In particular, the book shows how to use the law of mass balance and the law of mass action to derive an enzyme kinetic model - the Michaelis-Menten function or the Hill function, how to use a current-voltage relation, Nernst potential equilibrium equation, and Hodgkin and Huxley's models to model an ionic channel or pump, and how to use the law of mass balance to integrate these enzyme or channel models into a complete feedback control system. The book also illustrates how to use data to estimate parameters in a model, how to use MATLAB to solve a model numerically, how to do computer simulations, and how to provide model predictions. Furthermore, the book demonstrates how to conduct a stability and sensitivity analysis on a model.
The essential introduction to the principles and applications of feedback systems—now fully revised and expanded This textbook covers the mathematics needed to model, analyze, and design feedback systems. Now more user-friendly than ever, this revised and expanded edition of Feedback Systems is a one-volume resource for students and researchers in mathematics and engineering. It has applications across a range of disciplines that utilize feedback in physical, biological, information, and economic systems. Karl Åström and Richard Murray use techniques from physics, computer science, and operations research to introduce control-oriented modeling. They begin with state space tools for analysis and design, including stability of solutions, Lyapunov functions, reachability, state feedback observability, and estimators. The matrix exponential plays a central role in the analysis of linear control systems, allowing a concise development of many of the key concepts for this class of models. Åström and Murray then develop and explain tools in the frequency domain, including transfer functions, Nyquist analysis, PID control, frequency domain design, and robustness. Features a new chapter on design principles and tools, illustrating the types of problems that can be solved using feedback Includes a new chapter on fundamental limits and new material on the Routh-Hurwitz criterion and root locus plots Provides exercises at the end of every chapter Comes with an electronic solutions manual An ideal textbook for undergraduate and graduate students Indispensable for researchers seeking a self-contained resource on control theory
This book provides an entry point into Systems Biology for researchers in genetics, molecular biology, cell biology, microbiology and biomedical science to understand the key concepts to expanding their work. Chapters organized around broader themes of Organelles and Organisms, Systems Properties of Biological Processes, Cellular Networks, and Systems Biology and Disease discuss the development of concepts, the current applications, and the future prospects. Emphasis is placed on concepts and insights into the multi-disciplinary nature of the field as well as the importance of systems biology in human biological research. Technology, being an extremely important aspect of scientific progress overall, and in the creation of new fields in particular, is discussed in 'boxes' within each chapter to relate to appropriate topics. - 2013 Honorable Mention for Single Volume Reference in Science from the Association of American Publishers' PROSE Awards - Emphasizes the interdisciplinary nature of systems biology with contributions from leaders in a variety of disciplines - Includes the latest research developments in human and animal models to assist with translational research - Presents biological and computational aspects of the science side-by-side to facilitate collaboration between computational and biological researchers
This advanced textbook is tailored for an introductory course in Systems Biology and is well-suited for biologists as well as engineers and computer scientists. It comes with student-friendly reading lists and a companion website featuring a short exam prep version of the book and educational modeling programs. The text is written in an easily accessible style and includes numerous worked examples and study questions in each chapter. For this edition, a section on medical systems biology has been included.
Multivariable Feedback Control: Analysis and Design, Second Edition presents a rigorous, yet easily readable, introduction to the analysis and design of robust multivariable control systems. Focusing on practical feedback control and not on system theory in general, this book provides the reader with insights into the opportunities and limitations of feedback control. Taking into account the latest developments in the field, this fully revised and updated second edition: * features a new chapter devoted to the use of linear matrix inequalities (LMIs); * presents current results on fundamental performance limitations introduced by RHP-poles and RHP-zeros; * introduces updated material on the selection of controlled variables and self-optimizing control; * provides simple IMC tuning rules for PID control; * covers additional material including unstable plants, the feedback amplifier, the lower gain margin and a clear strategy for incorporating integral action into LQG control; * includes numerous worked examples, exercises and case studies, which make frequent use of Matlab and the new Robust Control toolbox. Multivariable Feedback Control: Analysis and Design, Second Edition is an excellent resource for advanced undergraduate and graduate courses studying multivariable control. It is also an invaluable tool for engineers who want to understand multivariable control, its limitations, and how it can be applied in practice. The analysis techniques and the material on control structure design should prove very useful in the new emerging area of systems biology. Reviews of the first edition: "Being rich in insights and practical tips on controller design, the book should also prove to be very beneficial to industrial control engineers, both as a reference book and as an educational tool." Applied Mechanics Reviews "In summary, this book can be strongly recommended not only as a basic text in multivariable control techniques for graduate and undergraduate students, but also as a valuable source of information for control engineers." International Journal of Adaptive Control and Signal Processing
How can we understand the complexity of genes, RNAs, and proteins and the associated regulatory networks? One approach is to look for recurring types of dynamical behavior. Mathematical models prove to be useful, especially models coming from theories of biochemical reactions such as ordinary differential equation models. Clever, careful experiments test these models and their basis in specific theories. This textbook aims to provide advanced students with the tools and insights needed to carry out studies of signal transduction drawing on modeling, theory, and experimentation. Early chapters summarize the basic building blocks of signaling systems: binding/dissociation, synthesis/destruction, and activation/inactivation. Subsequent chapters introduce various basic circuit devices: amplifiers, stabilizers, pulse generators, switches, stochastic spike generators, and oscillators. All chapters consistently use approaches and concepts from chemical kinetics and nonlinear dynamics, including rate-balance analysis, phase plane analysis, nullclines, linear stability analysis, stable nodes, saddles, unstable nodes, stable and unstable spirals, and bifurcations. This textbook seeks to provide quantitatively inclined biologists and biologically inclined physicists with the tools and insights needed to apply modeling and theory to interesting biological processes. Key Features: Full-color illustration program with diagrams to help illuminate the concepts Enables the reader to apply modeling and theory to the biological processes Further Reading for each chapter High-quality figures available for instructors to download