This IMA Volume in Mathematics and its Applications MATHEMATICAL APPROACHES TO BIOMOLECULAR STRUCTURE AND DYNAMICS is one of the two volumes based on the proceedings of the 1994 IMA Sum mer Program on "Molecular Biology" and comprises Weeks 3 and 4 of the four-week program. Weeks 1 and 2 appeared as Volume 81: Genetic Mapping and DNA Sequencing. We thank Jill P. Mesirov, Klaus Schulten, and De Witt Sumners for organizing Weeks 3 and 4 of the workshop and for editing the proceedings. We also take this opportunity to thank the National Institutes of Health (NIH) (National Center for Human Genome Research), the National Science Foundation (NSF) (Biological Instrumen tation and Resources), and the Department of Energy (DOE), whose fi nancial support made the summer program possible. A vner Friedman Robert Gulliver v PREFACE The revolutionary progress in molecular biology within the last 30 years opens the way to full understanding of the molecular structures and mech anisms of living organisms. Interdisciplinary research in mathematics and molecular biology is driven by ever growing experimental, theoretical and computational power. The mathematical sciences accompany and support much of the progress achieved by experiment and computation as well as provide insight into geometric and topological properties of biomolecular structure and processes. This volume consists of a representative sample of the papers presented during the last two weeks of the month-long Institute for Mathematics and Its Applications Summer 1994 Program in Molecular Biology."

Process integration has been one of the most active research fields in Biochemical Engineering over the last decade and it will continue to be so if bioprocessing is to become more rational, efficient and productive. This volume outlines what has been achieved in recent years. Written by experts who have made important contributions to the European Science, Foundation Program on Process Integration in Biochemical Engineering, the volume focuses on the progress made and the major opportunities, and in addition on the limitations and the challenges in bioprocess integration that lie ahead. The concept of bioprocess integration is treated at various levels, including integration at the molecular, biological, bioreactor and plant levels, but also accounting for the integration of separation and mass transfer operations and biology, fluid dynamics and physiology, as well as basic science and process technology.

Major advances have been made in recent years in clarifying the molecular properties of the cytochrome P-450 system. These advances stem, in practical terms, from the generally recognized importance of cytochrome P-450 in the metabolism of drugs and in the bioactivation of xenobiotics to toxic products. The fascinating multiplicity and differential regulation of cytochrome P-450 isozymes, and their ability to catalyze extraordinarily difficult chemical transformations, have independently drawn many chemists and biochemists into the P-450 circle. Progress in the field, from a technical point of view, has been propelled by the de velopment of reliable procedures for the purification of membrane-bound enzymes, by the growing repertoire of molecular biological techniques, and by the development of chemical models that mimic the catalytic action of P-450. As a result, our understanding of the P-450 system is moving from the descriptive, pharmacological level into the tangible realm of atomic detail. The rapid progress and multidisciplinary character of the cytochrome P-450 field, which cuts across the lines that traditionally divide disciplines as diverse as inorganic chemistry and genetics, have created a need for an up-to-date evaluation of the advances that have been made. It is hoped that this book, with its molecular focus on the cytochrome P-450 system, will alleviate this need. The authors of the individual chapters have strived to emphasize recent results without sacrificing the background required to make their chapters comprehensible to informed nonspecialists.

"Bioluminescent Imaging: Methods and Protocols" distills a wide range of techniques that use bioluminescence imaging as a tool for visualizing and tracking various biological processes. Covering diverse fields such as cellular and molecular biology, oncology, neurology, infectious diseases, immunology, and others, the detailed chapters of this volume are arranged by topic and describe practical procedures and applications of different bioluminescent reporters, from photoproteins (Aequorin) to bacterial luciferases as well as other secreted (such as Gaussia) and non-secreted luciferases (such as Firefly). Written in the highly successful "Methods in Molecular Biology" series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and expert tips for troubleshooting and avoiding known pitfalls.

Authoritative and cutting-edge, "Bioluminescent Imaging: Methods and Protocols" aims to provide diverse and comprehensive techniques to researchers interested in implementing bioluminescence-based imaging in their laboratory, regardless of their previous level of experience with such methodologies.

In response to the emergence of pathogenic bacteria that cannot be treated with current antibiotics, many researchers are revisiting the use of bacteriophages, or phages, to fight multidrug-resistant bacteria. Bacteriophage as Antibiotics: Molecular Biology and Applications provides unparalleled, comprehensive information on bacteriophages and their applications, such as phage therapy. It offers techniques, media, and methodology involved in isolating and working with therapeutic phages. Photographs, line drawings, and electron micrographs of phages are also included. With its broad approach, this book is a useful reference for microbiologists, hematologists, and infectious disease researchers.

Corpora non agunt nisi fixata. This old saying of Ehrlich's describing the physi- ological role of receptors and their ligands might be paraphrased into Corpora non ambulant nisi fixata when considering lipid transport between and within cells. Volume 16 of Subcellular Biochemistry is intended to bring the reader up to date with this young field. Indeed, lipid transfer proteins have only recently become the subject of a more systematic study. In this book the current status and the emerging trends are discussed. Chapters cover protein-mediated transfer of fatty acids, phospholipids, phosphatidylinositol, glycolipids, dolichol, retinoids, and cholesterol in animal, plant, yeast, and other eukaryotic cells. Details are included of the study of lipid transport proteins by means of fluorescent phos- pholipid analogues and of the lipid transfer proteins as probes of membrane structure and function, as well as spontaneous lipid transfer as it occurs between biological membranes. Some of the chapters should be read in conjunction with Volume 13 of this series, devoted to fluorescence studies on biological mem- branes, in particular Chapter 2 (Somerharju et al. ) concentrating on studies in which fluorescent phospholipid analogues have been used. Chapter 10 (Bill- heimer and Reinhart), dealing with cholesterol trafficking, should be compared with Chapter 12 of Volume 13 (Van Blitterswijk), pointing to the existence of a preferential association of cholesterol with sphingomyelin, which drags choles- terol to the plasma membrane. In one chapter (Chapter 8: Van Dessel et al.

Man-made carcinogens, natural genotoxic agents in the environment, as well as ionizing and ultraviolet radiation can damage DNA and are a constant threat to genome integrity. Throughout the evolution oflife, complex DNA repair systems have developed in all living organisms to cope with this damage. Unrepaired DNA lesions can promote genetic alterations (mutations) that may be linked to an altered phenotype, and, if growth-controlling genes are involved, these mutations can lead to cell transformation and the development of malignant tumors. Proto oncogenes and tumor suppressor genes may be critical targets for DNA damaging agents. In a number of animal model systems, correlations between exposure to a carcinogen, tumor develop ment, and genetic changes in tumor DNA have been established. To understand mutagenesis processes in more detail at the molecular level, we need to know the type and frequency of DNA adducts within cells, their distribution along genes and specific DNA sequences, as well as the rates at which they are repaired. We also need to know what types of mutations are produced and which gene positions are most prone to mutagenesis. This book provides a collection of techniques that are useful in mutagenesis research. The book is divided into three parts. In Part I, methods for DNA damage and repair analysis are provided."

In this anthology, leading researchers present critical reviews of methods and high-impact applications in computational biology that lead to results that also non-bioinformaticians must know to design efficient experimental research plans. Discovering Biomolecular Mechanisms with Computational Biology also summarizes non-trivial theoretical predictions for regulatory and metabolic networks that have received experimental confirmation. Discovering Biomolecular Mechanisms with Computational Biology is essential reading for life science researchers and higher-level students that work on biomolecular mechanisms and wish to understand the impact of computational biology for their success.

Biotechnology is a word that was originally coined to describe the new processes which could be derived from our ability to manipulate, in vitro, the genetic material common to all organisms. I t has now become a generic term encompassing all "applications" of living systems, including the more traditional fermentation and agricultural industries. Recombinant DNA technology has opened up new opportunities for the exploitation of microorganisms and animal and plant cells as producers or modifiers of chemical and biological products. This series of handbooks deals exclusively with microorganisms which are at the forefront of the new technologies and brings together in each of its volumes the background information necessary to appreciate the historical development of the organisms making up a particular genus, the degree to which molecular biology has opened up new opportunities, and the place they occupy in today's biotechnology industry. Our aim was to make this primarily a practical approach, with emphasis on methodology, combining for the first time information which has largely been spread across a wide literature base or only touched upon briefly in review articles. Each handbook should provide the reader with a source text, from which the importance of the genus to his or her work can be identified, and a practical guide to the handling and exploitation of the organisms included.

Providing experimental methods and protocols for performing pheromone research in a variety of organisms ranging from invertebrates to vertebrates, Pheromone Signaling: Methods and Protocols covers a wide spectrum of experimental approaches necessary for handling pheromone molecules, measuring receptor response and neural activation, and analyzing behavioral output. A great deal of progress has been made in understanding the molecular mechanisms underlying pheromone action, largely due to the discovery of receptor genes, the advancement of imaging techniques, and key multi-disciplinary approaches including aspects of organic chemistry, biochemistry, molecular biology, electrophysiology, and behavioral science. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips for troubleshooting and avoiding known pitfalls. Authoritative and practical, Pheromone Signaling: Methods and Protocols details the key methodologies utilized in laboratories all over the world, making them accessible to those who want to begin investigation in the area of pheromone research.

Principles and Reactions of Protein Extraction, Purification, and Characterization provides the mechanisms and experimental procedures for classic to cutting-edge techniques used in protein extraction, purification, and characterization. The author presents the principles and reactions behind each procedure and uses tables to compare the different methods. The book also discusses the development of antibodies and immunochemical techniques as tools for characterizing proteins and modified proteins such as glycoproteins. Helpful illustrations, diagrams, and tables effectively transform theoretical concepts into practical knowledge. Along with methodical working procedures for most techniques, the book also offers useful advice on which technique to use and when to apply a particular method. Presenting the advantages and disadvantages of the various protein techniques, Principles and Reactions of Protein Extraction, Purification, and Characterization enables students and researchers to master the mechanisms behind the protocols and choose the best method for their purposes.

Essentials of Medical Biochemistry, Third Edition offers a condensed, yet detailed overview of clinical biochemistry, spanning fundamentals and relevant physiologic and pathophysiologic concepts. Pivotal clinical case studies aid in understanding basic science in the context of diagnosis and treatment of human diseases, and the text illuminates key topics in molecular immunology and hemostasis. Users will find fundamental concepts aiding students and professionals in biochemistry, medicine, and other healthcare disciplines. The text is a useful refresher that will help users meet USMLE and other professional licensing examination requirements, providing thorough introductions, key points, multicolored illustrations of chemical structures and figures, fact-filled tables, and recommended reading lists. This Third Edition has been fully updated to address evolving techniques in the biological sciences, including genomics, metabolomics, transcriptomics, epigenomics, proteomics, and gene therapy, among other methods. In addition, each chapter has been fully revised for current science and now features learning objectives and chapter summaries, supplemental reading, and 5 clinical case based multiple choice questions. New clinical cases have been added throughout.

This is the third Proceedings book to arise from biennial conferen- ces on the Trace Amines. Since our first meeting in 1983 in Edmonton, Canada, progress has been brisk and, as will be seen from the ensuing pages, it is now possible to include major contributions from inverte- brate neurobiologists as well as receptorologists. In the opening ses- sion we heard about the distribution of the trace amines-now clear- ly a misnomer-in insects and the pharmacological, receptor, and syn- aptic characteristics of octopamine and tryptamine as well as the pos- sibility of monoamines in general being targets for insecticide discov- ery. In mammalian brain the distribution and characterization of the tryptamine receptor has proceeded to the point where two types have been described as well as novel agonists and antagonists, and, for the first time, a binding site for p-tyramine has been described. The com- bination of lesions and pharmacological and metabolic manipulations now permits the mapping of trace aminergic pathways, and the rap- idly accumulating evidence from releasing drugs, in situ microdialy- sis, iontophoresis, and second messenger systems lends credence to the claim that the trace amines possess neuromodulatory functions.

This volume introduces different concepts and methods of detecting RNA in biological material in a variety of model systems. The chapters in this book discuss methods that will answer numerous biological questions that arise in the study of RNAs. Some of the topics covered in this book are single mRNA molecule detection in embryos and neurons; detection of mRNA and associated molecules by ISH-IEM on frozen sections; optimizing molecular beacons for intracellular analysis of RNA; imaging translation dynamics of single mRNA molecules in live cells; preparation of high-throughput sequencing libraries; and capturing RNA binding proteins in embryos and in cell-culture. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, RNA Detection: Methods and Protocols is a valuable resource for novel and experiences scientist in the expanding field of RNAs.

Bio-inoculants in Horticultural Crops, Volume Three in the Advances in Bio-inoculant Sciences series, focuses on real-time application of novel microbes that have been proven to enhance and improve plant health and productivity. The book provides comprehensive information on a range of biological approaches and mechanisms for the improvement of horticultural crops being practiced in different production systems. Covering the subject from historical developments to recent advances in microbial interventions, it addresses the potential role and bio-mechanism of bio-inoculants for challenges including stress tolerance, production, commercialization, application methodology, challenges and future roadmap for sustainable production system of horticultural crops. This volume will be useful to scientists, academicians, and students of horticulture, agriculture microbiology, plant protection, and other related subjects.

Cells can be funny. Try to grow them with a slightly wrong recipe, and they turn over and die. But hit them with an electric field strong enough to knock over a horse, and they do enough things to justify international meetings, to fill a sizable book, and to lead one to speak of an entirely new technology for cell manipulation. The very improbability of these events not only raises questions about why things happen but also leads to a long list of practical systems in which the application of strong electric fields might enable the merger of cell contents or the introduction of alien but vital material. Inevitably, the basic questions and the practical applications will not keep in step. The questions are intrinsically tough. It is hard enough to analyze the action of the relatively weak fields that rotate or align cells, but it is nearly impossible to predict responses to the cell-shredding bursts of electricity that cause them to fuse or to open up to very large molecular assemblies. Even so, theoretical studies and systematic examination of model systems have produced some creditable results, ideas which should ultimately provide hints of what to try next.

Authoritative researchers and clinicians review our latest understanding of andrology in both basic science and clinical medicine. Topics range from explaining the biology of androgens-from several different perspectives-to illuminating their role in the development and modulation of physiologic systems. Authors demonstrate in a number of cases that testosterone can be a useful adjunct to the treatment of a variety of disease states. Other chapters consider important topics such as androgens use in athletes, the potential of androgens to improve physical function and quality of life in older men, and androgens as potential male contraceptives.

Proceedings of the NATO Advanced Study Institute, Pugnochiuso, Italy, June 22-July 3, 1986

The assimilation of sulfur in higher plants and its reduction in metabolically important sulfur compounds are crucial factors determining plant growth and vigor and resistance to stresses. The present book discusses the aspects of sustainable crop production with sulfur, the importance of sulfur metabolites and sulfur metabolizing enzymes in abiotic stress management in plants. The book provides the most up-to-date reference on sulfur assimilation in plants.

Explains models from natural flash systems Discusses theoretical considerations of flash systems Presents approaches and procedures for designing synthetic flash systems Explores methods for preparing flash systems for specific applications The design of environment-sensitive devices for biomedical and pharmaceutical applications has improved significantly due to recent advances in smart polymer and hydrogel technology. Despite their capacity to carry out functions that previously were unobtainable, smart polymers and hydrogels tend to have painfully slow response times. On the other hand biological systems go through phase changes at an extremely fast rate. This book examines the natural systems that respond almost instantaneously to environmental stimuli, and thus gives the reader an understanding of the mechanisms that govern these responses. The book includes chapters on how to go about designing a synthetic "flash" system based on the naturally occurring systems. It also deals with potential applications of flash systems in biomedical and pharmaceutical areas.

"Molecular Pharmacognosy" discusses the application of molecular biology in resource science and authentication of traditional Chinese medicine (TCM). This book reviews the latest developments in pharmacognosy, introduces a series of new views and insights, presents the hotspots and focus of the field of study on molecular pharmacognosy, and predicts a new direction of study on the resource science of TCM. Furthermore, the book also provides an open communications platform for the development of molecular pharmacognosy. This book is intended for biomedical scientists and researchers in the fields of molecular biology, traditional medicine and natural pharmaceutics.

Professor Lu-qi Huang is Director of the Collaborating Centre of the World Health Organization for Traditional Medicine (Chinese Materia Medica) and Vice-Chairman of the Australia Chinese Association for Biomedical Sciences Inc.

Cardiac Markers is a comprehensive, up-to-date summary of clinical information on serum cardiac markers for coronary artery disease. This book reviews in detail the biochemistry, clinical significance, and analytical measurements for each marker, as well as the advantages and limitations of existing and proposed markers. Comprehensive descriptions of therapeutic approaches to manage patients are presented. Also included are up-to-date listings of primary references and commercial methodologies, the latest data on the pathophysiology of unstable angina, and a discussion of the new emergency-room chest pain centers. Anyone who needs to know how to examine, diagnose, treat, and manage patients with acute chest pain and heart attacks will find this book indispensable.

This book evolved from a graduate course on applications of statistical thermody- namics to biochemical systems. Most of the published papers and books on this subject used in the course were written by experimentalists who adopted the phenomenological approach to describe and interpret their results. Two outstanding papers that impressed me deeply were the c1assical papers by Monod, Changeux, and Jacob (1963) and Monod, Wyman, and Changeux (1965), where the allosteric model for regulatory enzymes was introduced. Reading through them I feIt as if they were revealing one of the c1everest and most intricate tricks of nature to regulate biochemical processes. In 1985 I was glad to see T. L. HilI's volume entitled Cooperativity Theory in Biochemistry, Steady State and Equilibrium Systems. This was the fIrst book to systematically develop the molecular or statistical mechanical approach to binding systems. HilI demonstrated how and why the molecular approach is so advanta- geous relative to the prevalent phenomenological approach of that time. On page 58 he wrote the following (my italics): The naturalness of Gibbs' grand partition function for binding problems in biology is evidenced by the rediscovery of what is essentially the grand partition function for this particular type of problem by various physical biochentists, including E. Q. Adams, G.

Expert laboratory and clinical researchers from around the world review how to design and evaluate studies of tumor markers and examine their use in breast cancer patients. The authors cover both the major advances in sophisticated molecular methods and the state-of-the-art in conventional prognostic and predictive indicators. Among the topics discussed are the relevance of rigorous study design and guidelines for the validation studies of new biomarkers, gene expression profiling by tissue microarrays, adjuvant systemic therapy, and the use of estrogen, progesterone, and epidermal growth factor receptors as both prognostic and predictive indicators. Highlights include the evaluation of HER2 and EGFR family members, of p53, and of UPA/PAI-1; the detection of rare cells in blood and marrow; and the detection and analysis of soluble, circulating markers.

These proceedings bring together diverse disciplines that study nitrogen fixation and describe the most recent advances made in various fields: chemists are now studying FeMoco, the active site of nitrogenase in non-protein surroundings, and have refined the crystal structure of the enzyme to 1.6 angstroms.