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This book presents applications of geometric optimal control to real life biomedical problems with an emphasis on cancer treatments. A number of mathematical models for both classical and novel cancer treatments are presented as optimal control problems with the goal of constructing optimal protocols. The power of geometric methods is illustrated with fully worked out complete global solutions to these mathematically challenging problems. Elaborate constructions of optimal controls and corresponding system responses provide great examples of applications of the tools of geometric optimal control and the outcomes aid the design of simpler, practically realizable suboptimal protocols. The book blends mathematical rigor with practically important topics in an easily readable tutorial style. Graduate students and researchers in science and engineering, particularly biomathematics and more mathematical aspects of biomedical engineering, would find this book particularly useful.
This collection of papers offers a broad synopsis of state-of-the-art mathematical methods used in modeling the interaction between tumors and the immune system. These papers were presented at the four-day workshop on Mathematical Models of Tumor-Immune System Dynamics held in Sydney, Australia from January 7th to January 10th, 2013. The workshop brought together applied mathematicians, biologists, and clinicians actively working in the field of cancer immunology to share their current research and to increase awareness of the innovative mathematical tools that are applicable to the growing field of cancer immunology. Recent progress in cancer immunology and advances in immunotherapy suggest that the immune system plays a fundamental role in host defense against tumors and could be utilized to prevent or cure cancer. Although theoretical and experimental studies of tumor-immune system dynamics have a long history, there are still many unanswered questions about the mechanisms that govern the interaction between the immune system and a growing tumor. The multidimensional nature of these complex interactions requires a cross-disciplinary approach to capture more realistic dynamics of the essential biology. The papers presented in this volume explore these issues and the results will be of interest to graduate students and researchers in a variety of fields within mathematical and biological sciences.
This book discusses the numerical treatment of delay differential equations and their applications in bioscience. A wide range of delay differential equations are discussed with integer and fractional-order derivatives to demonstrate their richer mathematical framework compared to differential equations without memory for the analysis of dynamical systems. The book also provides interesting applications of delay differential equations in infectious diseases, including COVID-19. It will be valuable to mathematicians and specialists associated with mathematical biology, mathematical modelling, life sciences, immunology and infectious diseases.
Since the 1950s control theory has established itself as a major mathematical discipline, particularly suitable for application in a number of research fields, including advanced engineering design, economics and the medical sciences. However, since its emergence, there has been a need to rethink and extend fields such as calculus of variations, differential geometry and nonsmooth analysis, which are closely tied to research on applications. Today control theory is a rich source of basic abstract problems arising from applications, and provides an important frame of reference for investigating purely mathematical issues. In many fields of mathematics, the huge and growing scope of activity has been accompanied by fragmentation into a multitude of narrow specialties. However, outstanding advances are often the result of the quest for unifying themes and a synthesis of different approaches. Control theory and its applications are no exception. Here, the interaction between analysis and geometry has played a crucial role in the evolution of the field. This book collects some recent results, highlighting geometrical and analytical aspects and the possible connections between them. Applications provide the background, in the classical spirit of mutual interplay between abstract theory and problem-solving practice.
Cancer is a complex adaptive dynamic system that causes both local and systemic failures in the patient. Cancer is caused by a number of gain-of-function and loss-of-function events, that lead to cells proliferating without control by the host organism over time. In cancer, the immune system modulates cancer cell population heterogeneity and plays a crucial role in disease outcomes. The immune system itself also generates multiple clones of different cell types, with some clones proliferating quickly and maturing into effector cells. By creating regulatory signals and their networks, and generating effector cells and molecules, the immune system recognizes and kills abnormal cells. Anti-cancer immune mechanisms are realized as multi-layer, nonlinear cellular and molecular interactions. A number of factors determine the outcome of immune system-tumor interactions, including cancer-associated antigens, immune cells, and host organisms.
Differential Equations
This book may be regarded as consisting of two parts. In Chapters I-IV we pre sent what we regard as essential topics in an introduction to deterministic optimal control theory. This material has been used by the authors for one semester graduate-level courses at Brown University and the University of Kentucky. The simplest problem in calculus of variations is taken as the point of departure, in Chapter I. Chapters II, III, and IV deal with necessary conditions for an opti mum, existence and regularity theorems for optimal controls, and the method of dynamic programming. The beginning reader may find it useful first to learn the main results, corollaries, and examples. These tend to be found in the earlier parts of each chapter. We have deliberately postponed some difficult technical proofs to later parts of these chapters. In the second part of the book we give an introduction to stochastic optimal control for Markov diffusion processes. Our treatment follows the dynamic pro gramming method, and depends on the intimate relationship between second order partial differential equations of parabolic type and stochastic differential equations. This relationship is reviewed in Chapter V, which may be read inde pendently of Chapters I-IV. Chapter VI is based to a considerable extent on the authors' work in stochastic control since 1961. It also includes two other topics important for applications, namely, the solution to the stochastic linear regulator and the separation principle.
With chapters on free boundaries, constitutive equations, stochastic dynamics, nonlinear diffusion–consumption, structured populations, and applications of optimal control theory, this volume presents the most significant recent results in the field of mathematical oncology. It highlights the work of world-class research teams, and explores how different researchers approach the same problem in various ways. Tumors are complex entities that present numerous challenges to the mathematical modeler. First and foremost, they grow. Thus their spatial mean field description involves a free boundary problem. Second, their interiors should be modeled as nontrivial porous media using constitutive equations. Third, at the end of anti-cancer therapy, a small number of malignant cells remain, making the post-treatment dynamics inherently stochastic. Fourth, the growth parameters of macroscopic tumors are non-constant, as are the parameters of anti-tumor therapies. Changes in these parameters may induce phenomena that are mathematically equivalent to phase transitions. Fifth, tumor vascular growth is random and self-similar. Finally, the drugs used in chemotherapy diffuse and are taken up by the cells in nonlinear ways. Mathematical Oncology 2013 will appeal to graduate students and researchers in biomathematics, computational and theoretical biology, biophysics, and bioengineering.
The first edition pioneered new territory in the literature as the only definitive text-reference devoted to cancer management by the internist or primary care physician. Now as more & more cancer patients are being managed by this group, the second edition of Medical Oncology: Basic Principles & Clinical Management comes at the ideal time. The book is completely revised with new material on: Cancer & Pregnancy, AIDS, integration of molecular biology of cancer & new biologic response modifiers, plus timely coverage of how to effectively manage the cancer patient in the office setting; expanded coverage of nursing in cancer & completely revamped section on supportive care.
This book gives a comprehensive treatment of the fundamental necessary and sufficient conditions for optimality for finite-dimensional, deterministic, optimal control problems. The emphasis is on the geometric aspects of the theory and on illustrating how these methods can be used to solve optimal control problems. It provides tools and techniques that go well beyond standard procedures and can be used to obtain a full understanding of the global structure of solutions for the underlying problem. The text includes a large number and variety of fully worked out examples that range from the classical problem of minimum surfaces of revolution to cancer treatment for novel therapy approaches. All these examples, in one way or the other, illustrate the power of geometric techniques and methods. The versatile text contains material on different levels ranging from the introductory and elementary to the advanced. Parts of the text can be viewed as a comprehensive textbook for both advanced undergraduate and all level graduate courses on optimal control in both mathematics and engineering departments. The text moves smoothly from the more introductory topics to those parts that are in a monograph style were advanced topics are presented. While the presentation is mathematically rigorous, it is carried out in a tutorial style that makes the text accessible to a wide audience of researchers and students from various fields, including the mathematical sciences and engineering. Heinz Schättler is an Associate Professor at Washington University in St. Louis in the Department of Electrical and Systems Engineering, Urszula Ledzewicz is a Distinguished Research Professor at Southern Illinois University Edwardsville in the Department of Mathematics and Statistics.