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Role of Proteases in the Pathophysiology of Neurodegenerative Diseases

Researchers seeking problems that offer more hope of success often avoid subjects that seem to be difficult to approach experimentally, or subjects for which experimental results are difficult to interpret. The breakdown part of protein turnover in vivo, particularly in nervous tissue, was such a subject in the past – it was difficult to measure and difficult to explore the mechanisms involved. For factors that influence protein metabolism, it was thought that protein content, function, and distribution are controlled only by the synthetic mechanisms that can supply the needed specificity and response to stimuli. The role of breakdown was thought to be only a general metabolic digestion, elimination of excess polypeptides. We now know that the role of breakdown is much more complex: it has multiple functions, it is coupled to turnover, and it can affect protein composition, function, and synthesis. In addition to eliminating abnormal proteins, breakdown has many modulatory functions: it serves to activate and inactivate enzymes, modulate membrane function, alter receptor channel properties, affect transcription and cell cycle, form active peptides, and much more. The hydrolysis of peptide bonds often involves multiple steps, many enzymes, and cycles (such as ubiquination), and often requires the activity of enzyme complexes. Their activation, modification, and inactivation can thus play an important role in biological functions, with numerous families of proteases participating. The specific role of each remains to be elucidated.

Staphylococcus aureus Infection and Disease (Infectious Agents and Pathogenesis)

Staphylococcus aureus is now acknowledged as being the most important bacterial pathogen of humans. It usually produces localized disease but can be rapidly invasive, spreading through the tissues, invading bone, and seeding the bloodstream to produce a fulminant picture of septic shock, disseminated intravascular coagulation, and rapid death. Moreover, most strains of staph infections are becoming resistant to most antibiotics, thus posing a significant problem for hospitals and health care facilities. This book, a volume in the Infectious Agents and Pathogenesis series, presents chapters by the major researchers in the field.

Strange Bedfellows: How Medical Jurisprudence Has Influenced Medical Ethics and Medical Practice

The pervasive influence of law on medical practice and clinical bioethics is often noted with a combination of exasperation and lamentation. Physicians and non-physician bioethicists, generally speaking, consider the willingness of courts, legislatures, and regulatory agencies to insinuate themselves into clinical practice and medical research to be a distinctly negative aspect of contemporary American society. They are quick to point out that their colleagues in other Western developed nations are not similarly afflicted, and that the situation which obtains elsewhere is highly preferable to the legalization and purported over-regulation of medicine that has taken place in the United States during the last fifty years. In this book I offer a decidedly different perspective. It is, admittedly, not entirely without personal and professional bias. Prior to becoming a fu- time academic, teaching bioethics in the setting of an academic medical center, I was, for nearly 20 years, an attorney specializing in health law. Even after earning a doctorate in philosophy, I was frequently considered to be the “resident lawyer” on the bioethics faculty, much more frequently looked to for my insights on the law than my perspective as one who had formally studied moral philosophy and applied ethics. I note this not out ofa sense of frustration or disappointment, but as confirmation that even among physicians and n- physician bioethicists, there is widespread recognition that the law does have important contributions to make in assessing the practice ofmedicine and the conduct of medical research.

Insect Cell Cultures: Fundamental and Applied Aspects (Current Applications of Cell Culture Engineering #2)

Human Identification: The Use Of Dna Markers (Contemporary Issues in Genetics and Evolution #4)

The ongoing debate on the use of DNA profiles to identify perpetrators in criminal investigations or fathers in paternity disputes has too often been conducted with no regard to sound statistical, genetic or legal reasoning. The contributors to Human Identification: The Use of DNA Markers all have considerable experience in forensic science, statistical genetics or jurimetrics, and many of them have had to explain the scientific issues involved in using DNA profiles to judges and juries. Although the authors hold differing views on some of the issues, they have all produced accounts which pay due attention to the, sometimes troubling, issues of independence of components of the profiles and of population substructures. The book presents the considerable evolution of ideas that has occurred since the 1992 Report of the National Research Council of the U.S. Audience: Indispensable to forensic scientists, laying out the concepts to all those with an interest in the use of genetic information. The chapters and exhaustive bibliography are vital information for all lawyers who must prosecute or defend DNA cases, and to judges trying such cases.

The Biostatistics Cookbook: The Most User-Friendly Guide for the Bio/Medical Scientist

We live in a very uncertain world. Variation surrounds our work. There is noise in our experiments, in our measurements, and in our test subjects. From all these sources of uncertainty and variation, we try to extract a coherent picture of very complex and sometimes dynamic, biological and chemical processes. In fact, one of our major challenges is to separate this signal, the 'real' biology or chemistry, from the noise. The tools developed to do this are called, collectively, biostatistics. Any tool, even a hammer, can be misused. This could result, at best, in inefficiency, and, at worst, in disaster. With the advent of newer, us- friendly statistical software packages, desk top computing, and point-a- click technologies, it is easier than ever to make mistakes in your analyses. The beauty of having access to so much computing power is that you can now enjoy ultimate flexibility in data processing: that can also be a problem. Ask your computer to produce a particular analysis, report or graphic, and that is exactly what you will get: if you happen to have asked for the wrong thing it will be produced just as quickly, and you will probably never know it was wrong. One aim of this handbook is to help you choose the correct tool for the job at hand, understand its strengths and weaknesses, and to help you recognize when you should seek expert advice. We describe biostatistics as a collection of tools for very good reasons.

Sturgeon biodiversity and conservation (Developments in Environmental Biology of Fishes #17)

Selected, reviewed and revised papers from the International Conference on Sturgeon Biodiversity and Conservation held at The American Museum of Natural History in New York on 28-30 July 1994

The Ecology of Cyanobacteria: Their Diversity in Time and Space

Cyanobacteria make a major contribution to world photosynthesis and nitrogen fixation, but are also notorious for causing nuisances such as dense and often toxic `blooms' in lakes and the ocean. The Ecology of Cyanobacteria: Their Diversity in Time and Space is the first book to focus solely on ecological aspects of these organisms. Its twenty-two chapters are written by some thirty authors, who are leading experts in their particular subject. The book begins with an overview of the cyanobacteria - or blue-green algae, for those who are not specialists - then looks at their diversity in the geological record and goes on to describe their ecology in present environments where they play important roles. Why is one of the key groups of organisms in the Precambrian still one of the most important groups of phototrophs today? The importance of ecological information for rational management and exploitation of these organisms for commercial and other practical purposes is also assessed. Accounts are provided of nuisances as well as the ecology of the commercially successful Spirulina and the role of cyanobacteria in ecosystem recovery from oil pollution. Many chapters include aspects of physiology, biochemistry, geochemistry and molecular biology where these help general understanding of the subject. In addition there are three chapters dealing specifically with molecular ecology. Thirty-two pages of colour photos incorporate about seventy views and light micrographs. These features make the book valuable to a wide readership, including biologists, microbiologists, geologists, water managers and environmental consultants. The book complements the highly successful The Molecular Biology of Cyanobacteria already published by Kluwer.

Advanced Organic Chemistry: Part A: Structure and Mechanisms (Advanced Organic Chemistry)

Since its original appearance in 1977, Advanced Organic Chemistry has found wide use as a text providing broad coverage of the structure, reactivity and synthesis of organic compounds. The Fourth Edition provides updated material but continues the essential elements of the previous edition. The material in Part A is organized on the basis of fundamental structural topics such as structure, stereochemistry, conformation and aromaticity and basic mechanistic types, including nucleophilic substitution, addition reactions, carbonyl chemistry, aromatic substitution and free radical reactions. The material in Part B is organized on the basis of reaction type with emphasis on reactions of importance in laboratory synthesis. As in the earlier editions, the text contains extensive references to both the primary and review literature and provides examples of data and reactions that illustrate and document the generalizations. While the text assumes completion of an introductory course in organic chemistry, it reviews the fundamental concepts for each topic that is discussed. The Fourth Edition updates certain topics that have advanced rapidly in the decade since the Third Edition was published, including computational chemistry, structural manifestations of aromaticity, enantioselective reactions and lanthanide catalysis. The two parts stand alone, although there is considerable cross-referencing. Part A emphasizes quantitative and qualitative description of structural effects on reactivity and mechanism. Part B emphasizes the most general and useful synthetic reactions. The focus is on the core of organic chemistry, but the information provided forms the foundation for future study and research in medicinal and pharmaceutical chemistry, biological chemistry and physical properties of organic compounds. The New Revised 5th Edition will be available shortly. For details, click on the link in the right-hand column.

3D QSAR in Drug Design: Ligand-Protein Interactions and Molecular Similarity (Three-Dimensional Quantitative Structure Activity Relationships #2)

Significant progress has been made in the study of three-dimensional quantitative structure-activity relationships (3D QSAR) since the first publication by Richard Cramer in 1988 and the first volume in the series. 3D QSAR in Drug Design. Theory, Methods and Applications, published in 1993. The aim of that early book was to contribute to the understanding and the further application of CoMFA and related approaches and to facilitate the appropriate use of these methods. Since then, hundreds of papers have appeared using the quickly developing techniques of both 3D QSAR and computational sciences to study a broad variety of biological problems. Again the editor(s) felt that the time had come to solicit reviews on published and new viewpoints to document the state of the art of 3D QSAR in its broadest definition and to provide visions of where new techniques will emerge or new appli- tions may be found. The intention is not only to highlight new ideas but also to show the shortcomings, inaccuracies, and abuses of the methods. We hope this book will enable others to separate trivial from visionary approaches and me-too methodology from in- vative techniques. These concerns guided our choice of contributors. To our delight, our call for papers elicited a great many manuscripts.

3D QSAR in Drug Design: Recent Advances (Three-Dimensional Quantitative Structure Activity Relationships #3)

Significant progress has been made in the study of three-dimensional quantitative structure-activity relationships (3D QSAR) since the first publication by Richard Cramer in 1988 and the first volume in the series, 3D QSAR in Drug Design. Theory, Methods and Applications, published in 1993. The aim of that early book was to contribute to the understanding and the further application of CoMFA and related approaches and to facilitate the appropriate use of these methods. Since then, hundreds of papers have appeared using the quickly developing techniques of both 3D QSAR and computational sciences to study a broad variety of biological problems. Again the editor(s) felt that the time had come to solicit reviews on published and new viewpoints to document the state of the art of 3D QSAR in its broadest definition and to provide visions of where new techniques will emerge or new appli- tions may be found. The intention is not only to highlight new ideas but also to show the shortcomings, inaccuracies, and abuses of the methods. We hope this book will enable others to separate trivial from visionary approaches and me-too methodology from in- vative techniques. These concerns guided our choice of contributors. To our delight, our call for papers elicited a great many manuscripts.

Peptides: Biology and Chemistry (Chinese Peptide Symposia)

The fourth Chinese Peptide Symposium, hosted by Peking University, was held at Chengdu, China on July 21 25, 1996 with 164 participants, including 45 scientists from abroad, representing 12 countries. The four day conference was both intense and spiritually rewarding. Our goal for CPS 96 was to provide a forum for the exchange of knowledge, cooperation and friendship between the international and Chinese scientific communities, and we believe this goal was met. The symposium consisted of 10 sessions with 55 oral and 78 poster presentations, including synthetic methods, molecular diversity and peptide libraries, structure and conformation of peptides and proteins, bioactive peptides, peptide immunology, De Novo design and synthesis of proteins and peptides, ligand receptor interactions, the chemistry biology interface and challenging problems in peptides. Theenthusiasticcooperationandexcellentcontributionsweregratifying andtheactive response of the invited speakers contributed to the success of the symposium. The presentations were of excellent caliber and represented the most current and significant aspects of peptide science. Dr. James P. Tam and Dr. Jie Cheng Xu were the recipients of ‘The Cathay Award’ sponsored by the H. H. Liu Education Foundation, offered for their seminal contributions in peptide science and the Chinese Peptide Symposium. Four outstanding young scientists were selected by the organizing committee to receive awards sponsored by Haikou Nanhai Pharmaceutical Industry Co. Ltd. (Zhong He Group).

New Developments and New Applications in Animal Cell Technology: Proceedings of the 15th ESACT Meeting

Animal cell technology is becoming an increasingly important part of biotechnology and many products are now used in human health care and for veterinary applications. However, there are many times more products actually in the developmental pipelines of the biotechnology industry, including various phases of clinical trials. The Proceedings of the 15th Meeting of the European Society for Animal Cell Technology (Tours, France, September 1997) presents the actual current state as well as New Developments and Applications in Animal Cell Technology for the benefit of society. These Proceedings represent both the current state and applications of animal cell technology and the way the technology is expanding into new areas to give a unique insight into new products and applications for human and animal health care.

Cancer Cell Lines Part 2 (Human Cell Culture #2)

Continuous cell lines derived from human cancers are the mostwidely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions offundamental importance to the relevanceof human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative oftumors at that site is naïve and misleading.

Peptides: Frontiers of Peptide Science (American Peptide Symposia #5)

The Fifteen American Peptide Symposium (15APS) was held in Nashville, Tennessee, on June 14-19, 1997. This biennial meeting was jointly sponsored by the American Peptide Society and Vanderbilt University. The attendance of 1,081 participants from 37 countries was lower than the two previously held Symposia. However, the number of participating countries was the largest. Thus, it was gratifying to see that this meeting retained both its international flavor and participant loyalty at a time when there are many more symposia held each year on similar subjects. The scientific program, thanks to the insights and efforts of the Program Committee as well as Dr. Peter Schiller, the President of the American Peptide Society, was extraordinarily rich, diverse, and exciting. It was comprised of 124 oral and 550 poster presentations. Three prominent format changes were installed. First, the Symposium started on Saturday instead of Sunday. Second, the program opened on Saturday afternoon with a Mini-symposium by the Young Investigators to give them an early start and attention. Finally, 40 short and definitive reports were given in two parallel sessions. The expanded format permitted an unprecedented number of lectures and enabled wider participation by the attending delegates.

Asking to Die: Inside The Dutch Debate About Euthanasia

claim was that he had faced a conflict of duties pitting his legal duty not to kill against his duty as a physician to relieve his patient’s unbearable suffering. He was acquitted on the important grounds of conflict of duty. These grounds are based on a concept in Dutch law called "force majeure" 4 which recognizes extenuating circumstances such as conflicts of duty. The acquittal was upheld by the Lower Court of Alkmaar, but revoked by an Amsterdam court of appeal. The case went on to the Supreme Court, but before the Supreme Court's decision was issued, the Royal Dutch Medical Association (RDMA) attempted to clarify the criteria for euthanasia that many within the profession already accepted. The RDMA proposed that physicians be permitted to perform euthanasia provided that a set of procedures had been met. Variously stated, the guidelines contain the following central provisions: Voluntary, competent, explicit, and persistent requests on the part of the • patient; Requests based on full information; • The patient is in a situation of intolerable and hopeless suffering (either • physical or mental); No further acceptable alternatives to euthanasia. All alternatives • acceptable to the patient for relief of suffering having been tried; Consultation with at least one other physician whose judgment can be • 5 expected to be independent. Indirectly, these guidelines became the criteria prosecutors used to decide whether or not to bring charges.

Peptide Science — Present and Future: Proceedings of the 1st International Peptide Symposium

In the late 1980s, Peptide Societies were established in Europe, the United States, and Japan, and more recently, in the Asian and the Pacific Rim regions including Australia, China, and Korea. At the time of the establishment of the American, European and Japanese Peptide Societies, the International Liaison Organizing Committee representing these Peptide Societies, along with the Australian Peptide Society, began discussions for holding international confer ences which would supercede or be held in lieu of the numerous individual meetings, held by the peptide societies of each individual country or region. The representative of the Chinese Peptide Society participated in these discus sion in the International Liaison Organizing Committee at the meeting of the American Peptide Symposium in Nashville, in June 1997. After lengthy discus sions over several years, we agreed to organize and host the International Peptide Symposium in Japan. The First International Peptide Symposium (IPS’97) was held on November 30–December 5, 1997, in Kyoto, and was co sponsored by four Peptide Societies. The attendance at this Symposium was 550 participants, including representatives from 32 different countries. We were very pleased with this outcome and anticipate an even larger attendance for forthcoming Symposia in future years. The revolution and advances in science and technology during the past two decades has caused traditional peptide chemistry to expand to peptide science, spreading from physical science to biology, pharmacology, and medicine.

Animal Cell Technology: Proceedings of the Tenth Annual Meeting of the Japanese Association for Animal Cell Technology, Nagoya, November 5–8, 1997 (Animal Cell Technology: Basic & Applied Aspects #1)

Animal cell technology is a growing discipline of cell biology which aims not only to understand structures, functions and behaviors of differentiated animal cells but also to ascertain their abilities to be used for industrial and medical purposes. The goal of animal cell technology includes accomplishments of clonal expansion of differentiated cells with useful ability, optimization of their culture conditions, modulation of their ability for production of medically and pharmaceutically important proteins, and the application of animal cells to gene therapy and artificial organs. This Volume gives the readers a complete review of the present state of the art in Japan. The Proceedings will be useful for cell biologists, biochemists, molecular biologists, immunologists, biochemical engineers and other disciplines related to animal cell culture, working either in academic environments or in industries of biotechnology and pharmacy.

Persons and Their Bodies: Rights, Responsibilities, Relationships (Philosophy and Medicine #60)

Debate regarding organ sales is largely innocent of the history of thought on the matter. This volume seeks to remedy this shortcoming. Positions for or against a market in human organs are nested within moral intuitions, ontological or political theoretical premises, or understandings of special moral concerns, such as permissible uses of the body, which have a long history of analysis. The essays compass the views of Plato, Aristotle, Aquinas, Locke, Kant, Hegel, Mill and Christianity, as well as particular methodological approaches, such as the phenomenology of the body, natural law theory, legal theory and libertarian critique of legal theory. These discussions cluster a number of conceptually independent philosophical concerns: (1) What is the appropriate understanding of the relationship between persons and their bodies? (2) What does it mean to `own' an organ? (3) Do governments have moral authority to regulate how persons use their own body parts? (4) What are the costs and benefits of a market in human organs? Such questions are related by an urgent public health challenge: the considerable disparity between the number of patients who could significantly benefit from organ transplantation and the number of human organs available for transplantation. This volume explores the theoretical, normative, and historical foundations for alternative policies for procurement and transplantation of human organs.

Confucian Bioethics (Philosophy and Medicine #61)

This volume explores Confucian views regarding the human body, health, virtue, suffering, suicide, euthanasia, `human drugs,' human experimentation, and justice in health care distribution. These views are rooted in Confucian metaphysical, cosmological, and moral convictions, which stand in contrast to modern Western liberal perspectives in a number of important ways. In the contemporary world, a wide variety of different moral traditions flourish; there is real moral diversity. Given this circumstance, difficult and even painful ethical conflicts often occur between the East and the West with regard to the issues of life, birth, reproduction, and death. The essays in this volume analyze the ways in which Confucian bioethics can clarify important moral concepts, provide arguments, and offer ethical guidance. The volume should be of interest to both general readers coming afresh to the study of bioethics, ethics, and Confucianism, as well as for philosophers, ethicists, and other scholars already familiar with the subject.

A Guide to Protein Isolation

It is a truism of science that the more fundamental the subject, the more universally applicable it is. Nevertheless, it is important to strike a level of “fundamentalness” appropriate to the task in hand. For -depth study of the mechanics of motor cars would tell one example, an in nothing about the dynamics of traffic. Traffic exists on a different “level” - it is dependent upon the existence of motor vehicles but the physics and mathematics of traffic can be adequately addressed by considering motor vehicles as mobile “blobs”,with no consideration of how they become mobile. To start a discourse on traffic with a consideration of the mechanics of motor vehicles would thus be inappropropriate. In writing this volume, I have wrestled with the question of the appropriate level at which to address the physics underlying many of the techniques used in protein isolation. I have tried to strike a level as would be used by a mechanic (with perhaps a slight leaning towards an engineer) - i.e. a practical level, offering appropriate insight but with minimal mathematics. Some people involved in biochemical research have a minimal grounding in chemistry and physics and so I have tried to keep it as simple as possible.

Animal Cell Technology: Proceedings of the joint international meeting of the Japanese Association for Animal Cell Technology (JAACT) and the European Society for Animal Cell Technology (ESACT) 1998, Kyoto, Japan

Animal cell technology aims to understand structures, functions, and behaviors of differentiated animal cells and to ascertain their abilities to be used in industrial and medical purposes. This volume gives readers a complete review of the present state of the art in Japan.

Primary Mesenchymal Cells (Human Cell Culture #5)

The human body contains many specialized tissues that are capable of fulfilling an incredible variety of functions necessary for our survival. This volume in the Human Cell Culture Series focuses on mesenchymal tissues and cells. The in vitro study of mesenchymal cells is perhaps the oldest form of human cell culture, beginning with the culturing of fibroblasts. Fibroblasts have long been generically described in the literature, arising from many tissue types upon in vitro cell culture. However, recent studies, many enabled by new molecular biology techniques, have shown considerable diversity in fibroblast type and function, as described within this volume. Mesenchymal tissue types that are described within include bone, cartilage, tendons and ligaments, muscle, adipose tissue, and skin (dermis). The proper function of these tissues is predominantly dependent upon the proper proliferation, differentiation, and function of the mesenchymal cells which make up the tissue. Recent advancements in primary human mesenchymal cell culture have led to remarkable progress in the study of these tissues. Landmark experiments have now demonstrated a stem cell basis for many of these tissues, and, furthermore, significant plasticity and inter-conversion of stem cells between these tissues, resulting in a great deal of contemporary excitement and controversy. Newly-developed mesenchymal cell culture techniques have even lead to novel clinical practices for the treatment of disease.

Building Bioethics: Conversations with Clouser and Friends on Medical Ethics (Philosophy and Medicine #62)

K. Danner Clouser is one of the most important figures in establishing and shaping the fields of medical ethics, bioethics, and the philosophy of education in the second half of the twentieth century. Clouser challenged many established approaches to moral theory and offered innovative strategies for integrating the humanities into professional education, especially that of physicians and nurses. The contributions published in Building Bioethics: Conversations with Clouser and Friends on Medical Ethics are unique both in their devotion to a critical review of his contributions, and in bringing together internationally known figures in bioethics, medical ethics, and philosophy of medicine to comment upon Clouser's work. These leaders of the field include Tom Beauchamp, Daniel Callahan, James Childress, Nancy Dubler, H. Tristram Engelhardt, Al Jonsen, Loretta Kopelman, Larry McCullough, John Moskop, and Robert Veatch. This book merits special attention from those interested in bioethics, philosophy of medicine, medical ethics, philosophy, medical education, religious studies, and nursing education.

Cancer Cell Lines Part 1 (Human Cell Culture #1)

Continuous cell lines derived from human cancers are the most widely used resource in laboratory-based cancer research. The first 3 volumes of this series on Human Cell Culture are devoted to these cancer cell lines. The chapters in these first 3 volumes have a common aim. Their purpose is to address 3 questions of fundamental importance to the relevance of human cancer cell lines as model systems of each type of cancer: 1. Do the cell lines available accurately represent the clinical presentation? 2. Do the cell lines accurately represent the histopathology of the original tumors? 3. Do the cell lines accurately represent the molecular genetics of this type of cancer? The cancer cell lines available are derived, in most cases, from the more aggressive and advanced cancers. There are few cell lines derived from low grade organ-confined cancers. This gap can be filled with conditionally immortalized human cancer cell lines. We do not know why the success rate for establishing cell lines is so low for some types of cancer and so high for others. The histopathology of the tumor of origin and the extent to which the derived cell line retains the differentiated features of that tumor are critical. The concept that a single cell line derived from a tumor at a particular site is representative of tumors at that site is naïve and misleading.