This book presents recent research results relating to applications of nonlinear dynamics, focusing specifically on four topics of wide interest: heart dynamics, DNA/RNA, cell mobility, and proteins. The book derives from the First BCAM Workshop on Nonlinear Dynamics in Biological Systems, held in June 2014 at the Basque Center of Applied Mathematics (BCAM). At this international meeting, researchers from different but complementary backgrounds, including molecular dynamics, physical chemistry, bio-informatics and biophysics, presented their most recent results and discussed the future direction of their studies using theoretical, mathematical modeling and experimental approaches. Such was the level of interest stimulated that the decision was taken to produce this publication, with the organizers of the event acting as editors. All of the contributing authors are researchers working on diverse biological problems that can be approached using nonlinear dynamics. The book will appeal especially to applied mathematicians, biophysicists, and computational biologists.

This book collects recent advances in the field of nonlinear dynamics in biological systems. Focusing on medical applications as well as more fundamental questions in biochemistry, it presents recent findings in areas such as control in chemically driven reaction-diffusion systems, electrical wave propagation through heart tissue, neural network growth, chiral symmetry breaking in polymers and mechanochemical pattern formation in the cytoplasm, particularly in the context of cardiac cells. It is a compilation of works, including contributions from international scientists who attended the “2nd BCAM Workshop on Nonlinear Dynamics in Biological Systems,” held at the Basque Center for Applied Mathematics, Bilbao in September 2016. Embracing diverse disciplines and using multidisciplinary approaches – including theoretical concepts, simulations and experiments – these contributions highlight the nonlinear nature of biological systems in order to be able to reproduce their complex behavior. Edited by the conference organizers and featuring results that represent recent findings and not necessarily those presented at the conference, the book appeals to applied mathematicians, biophysicists and computational biologists.

The book presents nine mini-courses from a summer school, Dynamics of Biological Systems, held at the University of Alberta in 2016, as part of the prestigious seminar series: Séminaire de Mathématiques Supérieures (SMS). It includes new and significant contributions in the field of Dynamical Systems and their applications in Biology, Ecology, and Medicine. The chapters of this book cover a wide range of mathematical methods and biological applications. They - explain the process of mathematical modelling of biological systems with many examples, - introduce advanced methods from dynamical systems theory, - present many examples of the use of mathematical modelling to gain biological insight - discuss innovative methods for the analysis of biological processes, - contain extensive lists of references, which allow interested readers to continue the research on their own. Integrating the theory of dynamical systems with biological modelling, the book will appeal to researchers and graduate students in Applied Mathematics and Life Sciences.

Early in 1990 a scientific committee was formed for the purpose of organizing a high-level scientific meeting on Future Directions of Nonlinear Dynamics in Physical and Biological Systems, in honor of Alwyn Scott's 60th birthday (December 25, 1991). As preparations for the meeting proceeded, they were met with an unusually broad-scale and high level of enthusiasm on the part of the international nonlinear science community, resulting in a participation by 168 scientists from 23 different countries in the conference, which was held July 23 to August 11992 at the Laboratory of Applied Mathematical Physics and the Center for Modelling, Nonlinear Dynamics and Irreversible Thermodynamics (MIDIT) of the Technical University of Denmark. During the meeting about 50 lectures and 100 posters were presented in 9 working days. The contributions to this present volume have been grouped into the following chapters: 1. Integrability, Solitons, and Coherent Structures 2. Nonlinear Evolution Equations and Diffusive Systems 3. Chaotic and Stochastic Dynamics 4. Classical and Quantum Lattices and Fields 5. Superconductivity and Superconducting Devices 6. Nonlinear Optics 7. Davydov Solitons and Biomolecular Dynamics 8. Biological Systems and Neurophysics. AI Scott has made early and fundamental contributions to many of these different areas of nonlinear science. They form an important subset of the total number of the papers and posters presented at the meeting. Other papers from the meeting are being published in a special issue of Physica D Nonlinear Phenomena.

I Principles 1 1 Models of Systems 3 1. 1 Systems. Models. and Modeling . . . . . . . . . . . . . . . . . . . . 3 1. 2 Uses of Scientific Models . . . . . . . . . . . . . . . . . . . . . . . . 4 1. 3 Example: Island Biogeography . . . . . . . . . . . . . . . . . . . . . 6 1. 4 Classifications of Models . . . . . . . . . . . . . . . . . . . . . . . . 10 1. 5 Constraints on Model Structure . . . . . . . . . . . . . . . . . . . . . 12 1. 6 Some Terminology . . . . . . . . . . . . . . . . . . . . . . . . . . . 12 1. 7 Misuses of Models: The Dark Side . . . . . . . . . . . . . . . . . . . 13 1. 8 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15 2 The Modeling Process 17 2. 1 Models Are Problems . . . . . . . . . . . . . . . . . . . . . . . . . . 17 2. 2 Two Alternative Approaches . . . . . . . . . . . . . . . . . . . . . . 18 2. 3 An Example: Population Doubling Time . . . . . . . . . . . . . . . . 24 2. 4 Model Objectives . . . . . . . . . . . . . . . . . . . . . . . . . . . . 28 2. 5 Exercises . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30 3 Qualitative Model Formulation 32 3. 1 How to Eat an Elephant . . . . . . . . . . . . . . . . . . . . . . . . . 32 3. 2 Forrester Diagrams . . . . . . . . . . . . . . . . . . . . . . . . . . . 33 3. 3 Examples . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36 3. 4 Errors in Forrester Diagrams . . . . . . . . . . . . . . . . . . . . . . 44 3. 5 Advantages and Disadvantages of Forrester Diagrams . . . . . . . . . 44 3. 6 Principles of Qualitative Formulation . . . . . . . . . . . . . . . . . . 45 3. 7 Model Simplification . . . . . . . . . . . . . . . . . . . . . . . . . . 47 3. 8 Other Modeling Problems . . . . . . . . . . . . . . . . . . . . . . . . 49 viii Contents . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3. 9 Exercises 53 4 Quantitative Model Formulation: I 4. 1 From Qualitative to Quantitative . . . . . . . . . . . . . . . . . Finite Difference Equations and Differential Equations 4. 2 . . . . . . . . . . . . . . . . 4. 3 Biological Feedback in Quantitative Models . . . . . . . . . . . . . . . . . . . . . . . . . . 4. 4 Example Model . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4. 5 Exercises 5 Quantitative Model Formulation: I1 81 . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. 1 Physical Processes 81 . . . . . . . . . . . . . . . 5. 2 Using the Toolbox of Biological Processes 89 . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. 3 Useful Functions 96 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. 4 Examples 102 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 5. 5 Exercises 104 6 Numerical Techniques 107 . . . . . . . . . . . . . . . . . . . . . . . 6. 1 Mistakes Computers Make 107 . . . . . . . . . . . . . . . . . . . . . . . . . . 6. 2 Numerical Integration 110 . . . . . . . . . . . . . . . . 6. 3 Numerical Instability and Stiff Equations 115 . . . . . . . . . . . . . .

This book is intended as a communication platform to bridge the cultural, conceptual, and technological gap among the key systems biology disciplines of biology, mathematics, and information technology. To support this goal, contributors were asked to adopts an approach that appeals to audiences from different backgrounds.

Through a series of examples from physics, engineering, biology and economics, this book illustrates the enormous potential for application of ideas and concepts from nonlinear dynamics and chaos theory. The overlap with examples published in other books is virtually equal to zero. The book takes the reader from detailed studies of bifurcation structures of relativity simple models to pattern formation in spatially extended systems. The book also discusses the different perspectives that nonlinear dynamics brings to different fields of science.

Since modeling multiscale phenomena in systems biology and neuroscience is a highly interdisciplinary task, the editor of the book invited experts in bio-engineering, chemistry, cardiology, neuroscience, computer science, and applied mathematics, to provide their perspectives. Each chapter is a window into the current state of the art in the areas of research discussed and the book is intended for advanced researchers interested in recent developments in these fields. While multiscale analysis is the major integrating theme of the book, its subtitle does not call for bridging the scales from genes to behavior, but rather stresses the unifying perspective offered by the concepts referred to in the title. It is believed that the interdisciplinary approach adopted here will be beneficial for all the above mentioned fields.

The growing impact of nonlinear science on biology and medicine is fundamentally changing our view of living organisms and disease processes. This book introduces the application to biomedicine of a broad range of interdisciplinary concepts from nonlinear dynamics, such as self-organization, complexity, coherence, stochastic resonance, fractals and chaos. It comprises 18 chapters written by leading figures in the field and covers experimental and theoretical research, as well as the emerging technological possibilities such as nonlinear control techniques for treating pathological biodynamics, including heart arrhythmias and epilepsy. This book will attract the interest of professionals and students from a wide range of disciplines, including physicists, chemists, biologists, sensory physiologists and medical researchers such as cardiologists, neurologists and biomedical engineers.

Nonlinear dynamics has been successful in explaining complicated phenomena in well-defined low-dimensional systems. Now it is time to focus on real-life problems that are high-dimensional or ill-defined, for example, due to delay, spatial extent, stochasticity, or the limited nature of available data. How can one understand the dynamics of such sys