First published in 1980. CRC Press is an imprint of Taylor & Francis.

Based on a very successful one-semester course taught at Harvard, this text teaches students in the life sciences how to use differential equations to help their research. It needs only a semester's background in calculus. Ideas from linear algebra and partial differential equations that are most useful to the life sciences are introduced as needed, and in the context of life science applications, are drawn from real, published papers. It also teaches students how to recognize when differential equations can help focus research. A course taught with this book can replace the standard course in multivariable calculus that is more usually suited to engineers and physicists.

Exploring Mathematical Modeling in Biology through Case Studies and Experimental Activities provides supporting materials for courses taken by students majoring in mathematics, computer science or in the life sciences. The book's cases and lab exercises focus on hypothesis testing and model development in the context of real data. The supporting mathematical, coding and biological background permit readers to explore a problem, understand assumptions, and the meaning of their results. The experiential components provide hands-on learning both in the lab and on the computer. As a beginning text in modeling, readers will learn to value the approach and apply competencies in other settings. Included case studies focus on building a model to solve a particular biological problem from concept and translation into a mathematical form, to validating the parameters, testing the quality of the model and finally interpreting the outcome in biological terms. The book also shows how particular mathematical approaches are adapted to a variety of problems at multiple biological scales. Finally, the labs bring the biological problems and the practical issues of collecting data to actually test the model and/or adapting the mathematics to the data that can be collected. - Presents a single volume on mathematics and biological examples, with data and wet lab experiences suitable for non-experts - Contains three real-world biological case studies and one wet lab for application of the mathematical models - Includes R code templates throughout the text, which are also available through an online repository, along with the necessary data files to complete all projects and labs

Deepen students' understanding of biological phenomenaSuitable for courses on differential equations with applications to mathematical biology or as an introduction to mathematical biology, Differential Equations and Mathematical Biology, Second Edition introduces students in the physical, mathematical, and biological sciences to fundamental modeli

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 . . . . . . . . . . . . . .

The past forty years have been the stage for the maturation of mathematical biolo~ as a scientific field. The foundations laid by the pioneers of the field during the first half of this century have been combined with advances in ap plied mathematics and the computational sciences to create a vibrant area of scientific research with established research journals, professional societies, deep subspecialty areas, and graduate education programs. Mathematical biology is by its very nature cross-disciplinary, and research papers appear in mathemat ics, biology and other scientific journals, as well as in the specialty journals devoted to mathematical and theoretical biology. Multiple author papers are common, and so are collaborations between individuals who have academic bases in different traditional departments. Those who seek to keep abreast of current trends and problems need to interact with research workers from a much broader spectrum of fields than is common in the traditional mono-culture disciplines. Consequently, it is beneficial to have occasions which bring together significant numbers of workers in this field in a forum that encourages the exchange of ideas and which leads to a timely publication of the work that is presented. Such an occasion occurred during January 13 to 16, 1990 when almost two hun dred research workers participated in an international conference on Differential Equations and Applications to Biology and Population Dynamics which was held in Claremont.

Mathematical Models in Biology is an introductory book for readers interested in biological applications of mathematics and modeling in biology. A favorite in the mathematical biology community, it shows how relatively simple mathematics can be applied to a variety of models to draw interesting conclusions. Connections are made between diverse biological examples linked by common mathematical themes. A variety of discrete and continuous ordinary and partial differential equation models are explored. Although great advances have taken place in many of the topics covered, the simple lessons contained in this book are still important and informative. Audience: the book does not assume too much background knowledge--essentially some calculus and high-school algebra. It was originally written with third- and fourth-year undergraduate mathematical-biology majors in mind; however, it was picked up by beginning graduate students as well as researchers in math (and some in biology) who wanted to learn about this field.

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.

This volume is dedicated to the memory of the 1996 Turing Award winner Amir Pnueli, who passed away in November 2009. The Festschrift contains 15 scientific articles written by leading scientists who were close to Amir Pnueli either as former students, colleagues or friends. The topics covered span the entire breadth of the scientific work of Amir Pnueli, with a focus on the development and the application of formal methods. Also included is the first chapter of the unpublished Volume III of Zohar Manna and Amir Pnueli’s work on the verification of reactive systems using temporal logic techniques.