This monograph has arisen out of a number of attempts spanning almost five decades to understand how one might examine the evolution of densities in systems whose dynamics are described by differential delay equations. Though the authors have no definitive solution to the problem, they offer this contribution in an attempt to define the problem as they see it, and to sketch out several obvious attempts that have been suggested to solve the problem and which seem to have failed. They hope that by being available to the general mathematical community, they will inspire others to consider-and hopefully solve-the problem. Serious attempts have been made by all of the authors over the years and they have made reference to these where appropriate.

This book deals with the application of mathematics in modeling and understanding physiological systems, especially those involving rhythms. It is divided roughly into two sections. In the first part of the book, the authors introduce ideas and techniques from nonlinear dynamics that are relevant to the analysis of biological rhythms. The second part consists of five in-depth case studies in which the authors use the theoretical tools developed earlier to investigate a number of physiological processes: the dynamics of excitable nerve and cardiac tissue, resetting and entrainment of biological oscillators, the effects of noise and time delay on the pupil light reflex, pathologies associated with blood cell replication, and Parkinsonian tremor. One novel feature of the book is the inclusion of classroom-tested computer exercises throughout, designed to form a bridge between the mathematical theory and physiological experiments. This book will be of interest to students and researchers in the natural and physical sciences wanting to learn about the complexities and subtleties of physiological systems from a mathematical perspective. The authors are members of the Centre for Nonlinear Dynamics in Physiology and Medicine. The material in this book was developed for use in courses and was presented in three Summer Schools run by the authors in Montreal.

This book gives a unified treatment of a variety of mathematical systems generating densities, ranging from one-dimensional discrete time transformations through continuous time systems described by integro-partial-differential equations. Examples have been drawn from a variety of the sciences to illustrate the utility of the techniques presented. This material was organized and written to be accessible to scientists with knowledge of advanced calculus and differential equations. In various concepts from measure theory, ergodic theory, the geometry of manifolds, partial differential equations, probability theory and Markov processes, and chastic integrals and differential equations are introduced. The past few years have witnessed an explosive growth in interest in physical, biological, and economic systems that could be profitably studied using densities. Due to the general inaccessibility of the mathematical literature to the non-mathematician, there has been little diffusion of the concepts and techniques from ergodic theory into the study of these "chaotic" systems. This book intends to bridge that gap.

This monograph has arisen out of a number of attempts spanning almost five decades to understand how one might examine the evolution of densities in systems whose dynamics are described by differential delay equations. Though the authors have no definitive solution to the problem, they offer this contribution in an attempt to define the problem as they see it, and to sketch out several obvious attempts that have been suggested to solve the problem and which seem to have failed. They hope that by being available to the general mathematical community, they will inspire others to consider-and hopefully solve-the problem. Serious attempts have been made by all of the authors over the years and they have made reference to these where appropriate.

This book analyzes the impact of quiescent phases on biological models. Quiescence arises, for example, when moving individuals stop moving, hunting predators take a rest, infected individuals are isolated, or cells enter the quiescent compartment of the cell cycle. In the first chapter of Topics in Mathematical Biology general principles about coupled and quiescent systems are derived, including results on shrinking periodic orbits and stabilization of oscillations via quiescence. In subsequent chapters classical biological models are presented in detail and challenged by the introduction of quiescence. These models include delay equations, demographic models, age structured models, Lotka-Volterra systems, replicator systems, genetic models, game theory, Nash equilibria, evolutionary stable strategies, ecological models, epidemiological models, random walks and reaction-diffusion models. In each case we find new and interesting results such as stability of fixed points and/or periodic orbits, excitability of steady states, epidemic outbreaks, survival of the fittest, and speeds of invading fronts. The textbook is intended for graduate students and researchers in mathematical biology who have a solid background in linear algebra, differential equations and dynamical systems. Readers can find gems of unexpected beauty within these pages, and those who knew K.P. (as he was often called) well will likely feel his presence and hear him speaking to them as they read.

This is a short and self-contained introduction to the field of mathematical modeling of gene-networks in bacteria. As an entry point to the field, we focus on the analysis of simple gene-network dynamics. The notes commence with an introduction to the deterministic modeling of gene-networks, with extensive reference to applicable results coming from dynamical systems theory. The second part of the notes treats extensively several approaches to the study of gene-network dynamics in the presence of noise-either arising from low numbers of molecules involved, or due to noise external to the regulatory process. The third and final part of the notes gives a detailed treatment of three well studied and concrete examples of gene-network dynamics by considering the lactose operon, the tryptophan operon, and the lysis-lysogeny switch. The notes contain an index for easy location of particular topics as well as an extensive bibliography of the current literature. The target audience of these notes are mainly graduates students and young researchers with a solid mathematical background (calculus, ordinary differential equations, and probability theory at a minimum), as well as with basic notions of biochemistry, cell biology, and molecular biology. They are meant to serve as a readable and brief entry point into a field that is currently highly active, and will allow the reader to grasp the current state of research and so prepare them for defining and tackling new research problems.

Rhythms of the heart and of the nervous and endocrine system, breathing, locomotory movements, sleep, circadian rhythms and tissue cell cycles are major elements of the temporal order of man. The dynamics of these systems are characterized by changes in the properties of an oscillator, transitions from oscillatory states into chaotic or stationary states, and vice versa, coupling or uncoupling between two or more oscillators. Any deviation from the normal range to either more or less ordered states may be defined as temporal disorder. Pathological changes of temporal organization, such as tremor, epileptic seizures, Cheyne-Stokes breathing, cardiac arrhythmicities and circadian desynchronization, may be caused by small changes in the order (control) parameters. One major aspect of the symposium was the analysis of characteristic features of these temporal control systems, including nonlinear dynamics of interactions, positive, negative and mixed feedback systems, temporal delays, and their mathematical description and modelling. The ultimate goal is a better understanding of the principles of temporal organization in order to treat periodic diseases or other perturbations of "normal" dynamics in human oscillatory systems.

Introduces concepts from nonlinear dynamics using an almost exclusively biological setting for motivation, and includes examples of how these concepts are used in experimental investigations of biological and physiological systems. One novel feature of the book is the inclusion of classroom-tested computer exercises. This book will appeal to students and researchers working in the natural and physical sciences wanting to learn about physiological systems from a mathematical perspective.

The Second Law of Thermodynamics has been called the most important law of nature: It is the law that gives a direction to processes that is not inherent in the laws of motion, that says the state of the universe is driven to thermal equilibrium. Its mathematical formulation is simple: The entropy of a closed system cannot decrease. Since the recognition that macroscopic phenomena have an atomic basis, it has remained a fundamental problem to reconcile the increase of entropy with the known reversibility of all the laws of microscopic physics. Professor Michael Mackey of McGill University here explores the dynamical basis for the Second Law, that is, he seeks to illuminate the fundamental dynamical properties required for the construction of a successful statistical mechanics. Aimed at physicists and applied mathematicians with an interest in the foundations of statistical mechanics, the book includes such new material as: a demonstration that the black body radiation law can be deduced from maximal entropy principles; a discussion of sufficient conditions for the existence of at least one state of thermodynamic equilibrium; a description of the behavior of entropy in asymptotically periodic systems; a necessary and sufficient condition for the evolution of entropy to a global maximum; and a presen- tation of the three main types of ergodic theorems and their proofs. He also explores the potential role of incomplete knowledge of dynamical variables, measurement imprecision, and the effects of noise in giving rise to entropy increases.

The first edition of this book was originally published in 1985 under the ti tle "Probabilistic Properties of Deterministic Systems. " In the intervening years, interest in so-called "chaotic" systems has continued unabated but with a more thoughtful and sober eye toward applications, as befits a ma turing field. This interest in the serious usage of the concepts and techniques of nonlinear dynamics by applied scientists has probably been spurred more by the availability of inexpensive computers than by any other factor. Thus, computer experiments have been prominent, suggesting the wealth of phe nomena that may be resident in nonlinear systems. In particular, they allow one to observe the interdependence between the deterministic and probabilistic properties of these systems such as the existence of invariant measures and densities, statistical stability and periodicity, the influence of stochastic perturbations, the formation of attractors, and many others. The aim of the book, and especially of this second edition, is to present recent theoretical methods which allow one to study these effects. We have taken the opportunity in this second edition to not only correct the errors of the first edition, but also to add substantially new material in five sections and a new chapter."

In an important new contribution to the literature of chaos, two distinguished researchers in the field of physiology probe central theoretical questions about physiological rhythms. Topics discussed include: How are rhythms generated? How do they start and stop? What are the effects of perturbation of the rhythms? How are oscillations organized in space? Leon Glass and Michael Mackey address an audience of biological scientists, physicians, physical scientists, and mathematicians, but the work assumes no knowledge of advanced mathematics.

Variation of rhythms outside normal limits, or appearance of new rhythms where none existed previously, are associated with disease. One of the most interesting features of the book is that it makes a start at explaining "dynamical diseases" that are not the result of infection by pathogens but that stem from abnormalities in the timing of essential functions. From Clocks to Chaos provides a firm foundation for understanding dynamic processes in physiology.

Written by a well-known professor of physiology at McGill University, this text presents an informative exploration of the basis of the Second Law of Thermodynamics, detailing the fundamental dynamic properties behind the construction of statistical mechanics. Geared toward physicists and applied mathematicians with an interest in the foundations of statistical mechanics, it is suitable for advanced undergraduate and graduate courses. Unabridged republication of the edition published by Springer-Verlag, New York, 1992.

This book shows how densities arise in simple deterministic systems. There has been explosive growth in interest in physical, biological and economic systems that can be profitably studied using densities. Due to the inaccessibility of the mathematical literature there has been little diffusion of the applicable mathematics into the study of these 'chaotic' systems. This book will help to bridge that gap. The authors give a unified treatment of a variety of mathematical systems generating densities, ranging from one-dimensional discrete time transformations through continuous time systems described by integro-partial differential equations. They have drawn examples from many scientific fields to illustrate the utility of the techniques presented. The book assumes a knowledge of advanced calculus and differential equations, but basic concepts from measure theory, ergodic theory, the geometry of manifolds, partial differential equations, probability theory and Markov processes, and stochastic integrals and differential equations are introduced as needed.