Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

Streptococci are Gram-positive bacteria that cause a wide spectrum of diseases, such as pharyngitis, necrotizing fasciitis and streptococcal toxic shock syndrome, as well as rheumatic fever and rheumatic heart disease as sequelae. Antibiotics alone have not been able to control the disease and in spite of many efforts an effective vaccine is not yet available. A prerequisite for novel and successful strategies for combating these bacteria is a complete understanding of the highly complex pathogenic mechanisms involved, which are analyzed in this volume. In ten chapters, prominent authors cover various aspects including streptococcal diseases and global burden, epidemiology, adaptation and transmission, and molecular mechanisms of different diseases, as well as sequelae, vaccine development and clinical management. This book will serve as a valuable reference work for scientists, students, clinicians and public health workers and provide new approaches to meeting the challenge of streptococcal diseases.

Most successful research fields will go through different stages of development before maturation and eventually gain general acceptance.

In the course of this development, it is important to periodically examine current progress, refocus goals, and explore new directions in the field. We believe the field of Cell-Printing (CP) has reached a stage when such an exercise is beneficial for all researchers involved.

A number of the CP techniques have reached certain successes in the laboratory and it is time to examine their current capabilities and limitations, and establish future goals and direction. This is the aspiration of the proposed book.

CP techniques have been developed to dispense cells in a controlled manner. In the first publication of successful mammalian CP, the author envisioned: "Potentially, multiple cell types can be placed at arbitrary positions with micrometer precision in an attempt to recapitulate the complex 3D cellular organization of native tissues."1 Since that time, many CP techniques have achieved the capability of placing multiple cell types at arbitrary positions with micrometer precision in two-dimensions (2D). This is an important achievement and a major milestone. However, the second part of the author s vision continues to elude us.

To recapitulate the complex 3D cellular organization of native tissues using CP is to conduct tissue engineering (TE). To engineer any tissue is a major endeavor in science, technology, and engineering. TE using CP requires 3D processing. A few CP techniques have demonstrated some 3D printing successes. But none have demonstrated the ability to print multiple cell types at arbitrary positions with micrometer precision in 3D. To achieve this capability will probably require new ideas, new materials, and advances in tissue biology as well as new technologies. Printing tissues and organs is a capability we should and need to achieve based on its potential application in science and especially medicine. The proposed book will be a venue for researchers from diverse backgrounds to showcase their work, address barriers ahead,

and brainstorm new trails towards achieving this capability.

TE is just one important goal to pursue for CP, and by no means the only one. CP techniques found application in other areas, for example, BioLP has been shown to produce protein arrays, sort cells, and microdissect malignant tissue. Developing applications beyond TE for CP techniques helps sustain CP development by attracting resources and recognition to the field. The proposed book will solicit ideas for potential applications for CP as well as review the applications

developed thus far.

The proposed book will consist of a collection of chapters from researchers in areas of CP and related fields. The chapters will be separated into three sections. The first section will be a review of the capability and development of established CP techniques and an introduction to any new CP techniques. The second section will focus on topics relating to achieving true 3D CP: ideas, strategies, materials, and technologies. The final section will focus on the applications of CP, both those already realized and those that hold potential for the future.

The most recent developments in research on hepatic encephalopathy, inborn hyperammonaemic syndromes and nitrogen metabolism, including clinical aspects, were presented by international acknowledged experts in this active research field at the 12th International Symposium on Hepatic Encephalopathy, which was held from June 1 to 4, 2005 in Solingen, Schloss Burg, Germany. This book comprehensively summarizes the most important novel issues on hepatic encephalopathy and nitrogen metabolism and is of interest not only for scientists in the field, but also for interested clinicians. This update of present knowledge will provide a platform for future research in the field of hepatic encephalopathy and nitrogen metabolism.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

These are indeed exciting times to be a microbiologist. With one of the buzzwords of the past decade-"Biodiversity," and microbes are reveling in the attention as they represent by far most of the biodiversity on Earth. Microbes can thrive in almost any environment where there is an exploitable energy source, and, as a result, the possible existence of microbial life elsewhere in the solar system has stimulated the imaginations of many. Extremophiles have taken center stage in these investigations, and thermophiles have taken on the lead roles. Consequently, in the past decade there has been a surge of interest and research in the Ecology, Biology, and Biotechnology of microorganisms from thermal environments. Many of the foundations of thermophile research were laid in Yellowstone National Park, primarily by the research of Professor Thomas Brock's laboratory in the late 1960s and early 1970s. The upper temperature for life was debated, the first thermophilic archeum discovered (although it was only later shown to be an archeum by ribosomal cataloging), and the extremes of light, temperature, pH on the physiology of microorga nisms were explored. Interest in thermophiles increased steadily in the 1970s, and with the discovery of deep-sea hydrothermal vents in 1977, thermophilic research began its expo nential explosion. The development of Taq polymerase in the polymerase chain reaction (peR) focused interest on the biotechnological potential of thermophilic microorganisms and on the thermal features in Yellowstone National Park."

The idea of editing this book was born in the winter of 1988/1989. Christian Endler was organizing the workshop 'Wasser und Information' (water and information) in Austria [1], and Jurgen Schulte was working on a publication of his results on atomic cluster stabilities and long-range electromagnetic interaction in atomic clusters. It was Franz Moser from the Technical University of Graz who brought these two together. After a talk that Moser had given in Bremen, Schulte explained to hirn his ideas about clusters and long range interaction, and his concern about reliable theories and experiments in research on ultra high dilutions (UHD) and homoeopathy. He was suggested to be a speaker at the Austrian workshop. Reviewing the contributions of this workshop and the current literature on UHD and homoeopathy, especially the PhD thesis by Giesela King [2] and the excellent survey by Marco Righetti [3], we decided to work on a book in order to critically encou rage more scientists to work and publish in this field with a high scientific standard. What we had in mind was a useful contribution to the goal to lift research on UHD and homoeo pathy to an internationally acceptable scientific standard, to encourage international scien tists to work in this area and to establish UHD and homoeopathy in academic science. Delayed by our individual academic careers in our specific fields, and delayed by lack of funds it took us about four years to finish this book.

This book covers a range of statistical methods useful in the analysis of medical data, from the simple to the sophisticated, and shows how they may be applied using the latest versions of S-PLUS and S-PLUS 6. In each chapter several sets of medical data are explored and analysed using a mixture of graphical and model fitting approaches. At the end of each chapter the S-PLUS script files are listed, enabling readers to reproduce all the analyses and graphics in the chapter. These script files can be downloaded from a web site. The aim of the book is to show how to use S-PLUS as a powerful environment for undertaking a variety of statistical analyses from simple inference to complex model fitting, and for providing informative graphics. All such methods are of increasing importance in handling data from a variety of medical investigations including epidemiological studies and clinical trials. The mix of real data examples and background theory make this book useful for students and researchers alike. For the former, exercises are provided at the end of each chapter to increase their fluency in using the command line language of the S-PLUS software. Professor Brian Everitt is Head of the Department of Biostatistics and Computing at the Institute of Psychiatry in London and Sophia Rabe-Hesketh is a senior lecturer in the same department. Professor Everitt is the author of over 30 books on statistics including two previously co-authored with Dr. Rabe-Hesketh.

Oxidation-reduction (i.e. redox) processes at the plasma membrane of any cell have been attracting more and more attention, both in basic and in applied research, since the first workshop dealing with the plasma membrane oxidoreductases was organized in Cordoba, Spain, in 1988. This evolution is evident considering the numerous cell functions performed by plasma membrane redox systems not only in healthy cells but also in cells that escaped from the normal metabolic control (e.g. cancer cells) and cells under attack by pathogens. Plasma membrane redox processes have now been demonstrated to play an essential role in growth control and defense mechanisms of these cells. The great importance of the plasma membrane redox systems originates in the fact that they are located in the membrane which is essentially the site of communication between the living cell and its environment. We may say that the plasma membrane can be considered as the "sensory part" of the cell. No chemical substance can enter the cell interior without interaction with the plasma membrane.

In the last ten years there has been a considerable increase of interest on the notion of the minimal cell. With this term we usually mean a cell-like structure containing the minimal and sufficient number of components to be defined as alive, or at least capable of displaying some of the fundamental functions of a living cell. In fact, when we look at extant living cells we realize that thousands of molecules are organized spatially and functionally in order to realize what we call cellular life. This fact elicits the question whether such huge complexity is a necessary condition for life, or a simpler molecular system can also be defined as alive. Obviously, the concept of minimal cell encompasses entire families of cells, from totally synthetic cells, to semi-synthetic ones, to primitive cell models, to simple biomimetic cellular systems. Typically, in the experimental approach to the construction of minimal the main ingredient is the compartment, lipid vesicles (liposomes) are used to host simple and complex molecular transformations, from single or multiple enzymic reactions, to polymerase chain reactions, to gene expression. Today this research is seen as part of the broader scenario of synthetic biology but it is rooted in origins of life studies, because the construction of a minimal cell might provide biophysical insights into the origins of primitive cells, and the emergence of life on earth. The volume provides an overview of physical, biochemical and functional studies on minimal cells, with emphasis to experimental approaches. 15 International experts report on their innovative contributions to the construction of minimal cells.

This book is a critical examination of certain basic issues and themes crucial to understanding how ethics currently interfaces with health care and biomedical research. Beginning with an overview of the field, it proceeds through a delineation of such key notions as trust and uncertainty, dialogue involving talk and listening, the vulnerability of the patient against the asymmetric power of the health professional, along with professional and individual responsibility. It emphasizes several themes fundamental to ethics and health care: (1) the work of ethics requires strict focus on the specific situational understanding of each involved person. (2) Moral issues, at least those intrinsic to each clinical encounter, are presented solely within the contexts of their actual occurrence; therefore, ethics must not only be practical but empirical in its approach. (3) Each particular situation is in its own way imprecise and uncertain and the different types and dimensions of imprecision and uncertainty are critical for everyone involved. (4) Finally, medicine and health care more broadly are governed by the effort to make sense of the healer's experiences with the patient, whose own experiences and interpretations are ingredient to what the healer seeks to understand and eventually treat. In addition to providing a way to develop ethical considerations in clinical life and research projects, the book proposes that narratives provide the finest way to state and grapple with these themes and issues, whether in classrooms or real-life situations. It concludes with a prospective analysis of newly emerging issues presented by and within the new genetics, which, together within a focus on the phenomenon of birth, leads to an clearer understanding of human life.

Drug-related problems in the elderly is intended to serve as a source of information and clinical support in geriatric pharmacotherapy for students as well as all health care professionals, e.g. physicians, nurses and pharmacists. Pharmacotherapy is of great importance to all mankind. Drugs are however powerful and must be handled appropriately. This is especially important for elderly patients. Drug-related problem is not a major subject in most university programmes in medicine or pharmacy. When there is no speci c course, there is often no book covering the topic. In our view, as teachers at various university courses, there has been a shortage of literature that re ects the most important aspects of drug-related problems in the elderly. Medical practitioners, nurses and pharmacists, need to have this knowledge to be able to serve their patients in the best way. This book covers most aspects of drug-related problems in the elderly. With b- ter knowledge of drug-related dif culties and risks we hope that elderly will have fewer drug-related problems and bene t more from their pharmacotherapy.

Statistical methods for clinical trials have been an area of active research in Biostatistics since the first modern clinical trials were mounted in 1946 by the British Medical Research Council in whooping cough and tuberculosis. Often, the participants in clinical trials suffer from potentially fatal chronic diseases, and it is especially important that these experiments in medical research use designs that are efficient, can be understood by physicians, policy makers and patients, respond quickly new ideas in medicine and statistics, and, perhaps above all, show respect for the complex and important ethical issues that arise in these settings. This book explores some recent thinking in designs for clinical trials, including alternative designs for phase I studies, interim monitoring for futility, adaptive designs based on accumulating outcome data, and designs of new, targeted therapies. The book is intended for both the statistical practitioner, who may be too busy to stay abreast of the literature on statistical methods, as well as statisticians conducting research in clinical trials.

At the forefront of life sciences today is the emerging discipline of chembiomolecular science. This new term describes the integration of the frontier fields of chemical biology, chemistry, and pharmacology. Chembiomolecular science aims to elucidate new biological mechanisms as potential drug targets and enhance the creation of new drug therapies. This book comprises the proceedings of the Uehara Memorial Foundation Symposium 2011, which focused on the most recent advances in chembiomolecular science made by leading experts in the field. The book is divided into three main topics. The first is the chemical approach to understanding complex biological systems on a molecular level using chemical compounds as a probe. The second describes the biological approach used to develop new lead drug compounds. The third focuses on the biological system that serves as the potential drug target, the beginning step in the process of developing new drugs. Replete with the latest research, the book will draw the attention of all scientists interested in the synergies between chemistry and biology to elucidate life on a molecular level and to promote drug discovery. Ultimately, the book helps promote the understanding of biological functions at the molecular level and create new pharmaceuticals that can contribute to improving human health.

Myelodysplastic syndromes (MDS) are the most common hematological malignancies involving mostly the elderly population. The major morbidity relates to patients' symptomatic cytopenias.MDS was previously named as "preleukemia " or " smoldering leukemia" as the lack of terminal cells in MDS and because about 25% of all cases progresses into acute myeloid leukemia. According to various reports the annual incidence of MDS ranges widely from 2-12 per 100.000, increasing to 30-50 cases per 100.000 among persons aged 70 or older. It is believed that the true incidence of MDS have been underestimated however it seems to be comparable to that for multiple myeloma and chronic lymphocytic leukemia. In the past decade much progress had been made; we know more on the disease pathology, there is more emphasis on the care and more targeted therapy had been invested. Athors provide updated knowledge in this book on all clinically important aspects of the disease. Hot topics of our days are discussed in chapters by outstanding and well known scientists from all over the world. We would offer this product both for medical students and postgraduates as well as for all who are interested in this very exciting and fast progressing field of hematology. With this work authors should call attention on the disease for decision makers in healt care systems as well.

This treatise had its origins in the authors' strong opinion that the discovery of new drugs, especially of innovative therapeutic agents, really does not happen as a spontaneous sequel to investiga tive research, no matter how penetrating such research may be. Rather, it seemed to us that the discovery of innovative therapeutic agents was a very active process, existing in and of itself, and demanding full attention-it was not simply a passive, dependent by-process of investigative research. And yet, many researchers some close confreres of the authors, others more distant-believed otherwise. We felt that their view reflected unrealistic thinking and that reality probably lay closer to what Beyer" maintained: We are taught to believe that if we can understand a disease it should be easy enough to figure out, say, the molecular configuration of a definitive receptor mechanism somewhere along the line and to design a specific drug . . . . And so we start out to understand the disease but never get around to doing much about therapy. The authors very soon realized that there was essentially no quantitive information available on just where and how innovative therapeutic agents were discovered. There were only anecdotal accounts, and these were able to be selected and presented in ways that could be used to defend any point of view."

Single Subject Designs in Biomedicine draws upon the rich history of single case research within the educational and behavioral research settings and extends the application to the field of biomedicine. Biomedical illustrations are used to demonstrate the processes of designing, implementing, and evaluating a single subject design. Strengths and limitations of various methodologies are presented, along with specific clinical areas of application in which these applications would be appropriate. Statistical and visual techniques for data analysis are also discussed. The breadth and depth of information provided is suitable for medical students in research oriented courses, primary care practitioners and medical specialists seeking to apply methods of evidence practice to improve patient care, and medical researchers who are expanding their methodological expertise to include single subject designs. Increasing awareness of the utility in the single subject design could enhance treatment approach and evaluation both in biomedical research and medical care settings.

Adhesion plays a major role in the bacterial lifestyle. Bacteria can adhere to organic and inorganic surfaces, to each other, and of course to host cells during pathogenesis. The focus of this book is: how are such adhesion phenomena best studied? Microbial genetics experiments have greatly enhanced our knowledge of what bacterial factors are involved in adhesion. For numerous reasons, though, biochemical and structural biology knowledge of the molecular interactions involved in adhesion are limited. One major problem has been a lack of interdisciplinary research and understanding in the field. On the one hand, the microbiologists lack detailed knowledge of the biophysical possibilities and have limited access to the frequently expensive instrumentation involved while on the other hand, the experts in these methods frequently do not have access to the biological materials, nor do they necessarily understand the biological questions to be answered. The purpose of this book is thus to overcome this gap in communication between researchers in biology, chemistry and physics and to display the many ways and means to investigate bacterial adhesion. We hope to stimulate new and ground-breaking research.

Clinical Trials and Tribulations evaluates the multiple layers of complexities around research management, also exploring current practices, challenges and future directions. The book provides answers to readers questions and problems through extensive use of real-world examples, case studies and lessons learned. Following an approach to provide pragmatic viewpoints as well as concepts and methodologies and its alignment with specific practices, the book explores paradigms between planning and conducting research in academia vs. healthcare vs. industry in the UK vs. Europe vs. America. It highlights practical solutions to real-world complex issues that have been documented by independent regulators. This will be an indispensable book for all staff working in clinical research within healthcare, academia and industry, as well as students intending to work in clinical trials.

Homeostasis. The health of an organism is influenced by external and internal changes that may lead to the loss of homeostasis. Under healthy conditions organisms compensate these changes. If compensation fails disease ensues. Attention will be paid to lifestyle, environmental changes, genetic makeup and health system. It willbe answered how lifestyle, environment, genetic makeup and social conditions help to maintain or upset the biological balance and lead to cancer.
Tumor formation. To understand this process the transfer of intracellular and the pathways of extracellular information (signal transduction) will be reviewed briefly. Loss of cellular balance may lead to cell death (.e.g. apoptosis) or to rapid cell growth of cells leading to tumor formation.
Metastasis. Animal tumor models serve to understand the spread of the primary tumor cells to distant locations of the organism. Different types of tumors and metastases will be reviewed. "

"HPV and Cancer" is a concise read that covers all aspects of the Human Papilloma Virus as it relates to human cancers. While written by professionals, it design to be understandable by those that are not in the field, yet it has the technical details that professionals want to stay abreast of this changing field. The book starts out the history of HPV and progresses into the molecular biology of the virus and our current understand of the structure and functions of the proteins and genes it encodes. We then look at the dynamic trends of this infectious agent in the human population, how it interacts with human cells, and the role it plays with other organisms to produce both benign and malignant tumors. Lastly, there is a discussion about a new vaccine for HPV and the hopes that are held by many to change the trends with this virus and the associated cancers it produces.

This book compiles and explores cutting-edge research in degenerative skeletal disorders, such as Duchenne muscular dystrophy and congenital myopathy, and new stem-cell based therapies and gene replacement therapy. Twelve expertly-authored chapters navigate the nuances of these treatments in an array of contexts and biological systems. The topics covered include: How are urine cells from a patient with Duchenne muscular dystrophy transformed into beating heart cells? What can reprogrammed cells tell us about heart muscle failure? What do gene mutations mean for those born with a muscle disease? How are manufacturing methods applied to human stem cells? Does therapeutic exercise benefit those patients who receive engineered limb muscle? Is there practical advice about nutrition to enhance muscle function for the Duchenne patient? Can microRNAs be useful to regenerate diseased muscle? Regenerative Medicine for Degenerative Muscle Diseases is ideal for scientists and clinicians from varying disciplines in genetics, cell biology, virology, cell-based manufacturing, rehabilitation medicine, nutrition, veterinary medicine and neurosurgery. The reader will see how transformative changes occur in medicine that can powerfully impact the future for patients suffering from inherited disorders affecting muscles of the body, including the heart.

Prediction models are important in various fields, including medicine, physics, meteorology, and finance. Prediction models will become more relevant in the medical field with the increase in knowledge on potential predictors of outcome, e.g. from genetics. Also, the number of applications will increase, e.g. with targeted early detection of disease, and individualized approaches to diagnostic testing and treatment. The current era of evidence-based medicine asks for an individualized approach to medical decision-making. Evidence-based medicine has a central place for meta-analysis to summarize results from randomized controlled trials; similarly prediction models may summarize the effects of predictors to provide individu- ized predictions of a diagnostic or prognostic outcome. Why Read This Book? My motivation for working on this book stems primarily from the fact that the development and applications of prediction models are often suboptimal in medical publications. With this book I hope to contribute to better understanding of relevant issues and give practical advice on better modelling strategies than are nowadays widely used. Issues include: (a) Better predictive modelling is sometimes easily possible; e.g. a large data set with high quality data is available, but all continuous predictors are dich- omized, which is known to have several disadvantages.

In the approach to the analysis of disease, including, of course, cancer, two major thrusts may be distinguished. These may be referred to, in shorthand, as agents and processes: the causative agents (chemical, microbial, physical, environmental, and psychosocial) and the organismic processes, initiated and furthered by the agents, culminating in observable pathology (at the macromolecular, cytological, histological, organ function, locomotor, and behavioral levels). The past 25 years, since the appearance of the first volume of the predecessor series (1) authored by the Editors of this present volume, have seen an impressive number of studies on chemicals (and other agents) as etiologic factors in the induction of cancer. The major emphasis has been on the discovery of many chemical carcinogens of widely different structures, their metabolism by various tissues and cells, and, in turn, their molecular-biochemical effects on the cells. This rapidly expanded body of information, as effectively covered in the predecessor volumes, is an excellent entree to the second half of the overall problem of chemical carcinogenesis, the processes. The active agents trigger a large array of molecular-biochemical alterations to which the target cells, target tissues, and target organisms respond in many select and common ways. This second major aspect of the induction of cancer by chemicals (and by other agents)- the sequence of cellular and tissue changes clearly relevant to cancer-remains the challenge for the future.

"Mycobacterium tuberculosis" is one of the most notorious pathogens on earth, causing the death of approximately 1.5 million people annually. A major problem in the fight against tuberculosis is the emergence of strains that have acquired resistance to all available antibiotics. One key to the success of "M. tuberculosis" as a pathogen is its ability to circumvent host immune responses at different levels. This is not only a result of the special makeup of "M. tuberculosis" in terms of genetic diversity and DNA metabolism and its possession of specialized secretion systems, but also of its ability to hijack the host s innate immune defence mechanisms.

In this volume, researchers from different disciplines provide a topical overview of the diverse mechanisms that contribute to the virulence of "M. tuberculosis," ranging from their genetic, metabolic and molecular makeup, as well as the complex strategies these bacteria utilize to escape immune destruction within infected hosts."