This book is a collection of articles written by prominent scientists who gathered in the city of Recife, Brazil, 23-27 October 2010, celebrating the 10th International Symposium on Yersinia. The event is held every four years in a different country and for the Yersinia 2010, an interesting and updated program covering advances in research in Yersiniae was organized. The major advances achieved over the past four years since the last symposium held in Lexington, USA in 2006 were divided into eight chapters: Epidemiology, Clinical, Diagnostic and Therapeutic aspects; Ecology and Modeling; Genomic/Transcriptomics and Large Scale Population; Immune Response and Vaccine; Pathogenesis and Pathogenicity Factors; Cellular Yersiniology; Bacterial Structure and Metabolism: Roles in Pathogenesis and Bacterial Life Style. The purpose of the book is to extend cutting edge knowledge on Yersinia discussed during the 10th International Symposium.

This volume explores the latest developments in a novel area of molecular biology and a hot topic in the field of oncology: cancer stem cells. These chapters from expert contributing authors present concepts such as the universal stem cell, new molecular pathways, new targeted agents, the different roles that cancer stem cells seem to have according to the organ they are placed in, and the future role that targeting cancer stem cells may have in the management of patients in the clinic.

Exploring the latest research including new data from randomized trials, this book examines important proposals over the origin of cancer stem cells such as the possibility that cancer stem cells may arise from mutated stem cells or a fully differentiated cell that may undergo several mutations that drive it back to a stem-like state. The authors consider the role that stem cells seem to have in the onset, development and resistance to classical antitumoral treatments of cancer and discuss possible potential future treatment modalities for the management of advanced cancer patients.

The question, "Are stem cells involved in cancer?" may not have a simple answer, but ongoing investigations, in-depth consideration and a broad spectrum of information can be found in this book, allowing the reader to arrive at his or her own answer.

This book will appeal to researchers in the field of oncology and cancer research and biomedical scientists with an interest in stem cells.

The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version.

I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition.

Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book.

In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling.

New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.

RNA technologies are the driving forces of modern medicine and biotechnology. They combine the fields of biochemistry, chemistry, molecular biology, cell biology, physics, nanotechnology and bioinformatics. The combination of these topics is set to revolutionize the medicine of tomorrow. After more than 15 years of extensive research in the field of RNA technologies, the first therapeutics are ready to reach the first patients. Thus we are witnessing the birth of a very exciting time in the development of molecular medicine, which will be based on the methods of RNA technologies. This volume is the first of a series. It covers various aspects of RNA interference and microRNAs, although antisense RNA applications, hammerhead ribozyme structure and function as well as non-coding RNAs are also discussed. The authors are internationally highly respected experts in the field of RNA technologies.

This book details all aspects of sequential clinical trials from preliminary planning, through the monitoring of the trial, to the final analysis of the results. Emphasis is placed on the triangular test and other procedures based on straight line stopping boundaries. These methods allow for frequent or occasional interim analyses and permit the analysis of a wide variety of patient responses. Alternative procedures are also covered in detail, and these include -spending function methods, repeated confidence intervals and Bayesian approaches to sequential clinical trials.

Managing the Drug Discovery Process: How to Make It More Efficient and Cost-Effective thoroughly examines the current state of pharmaceutical research and development by providing chemistry-based perspectives on biomedical research, drug hunting and innovation. The book also considers the interplay of stakeholders, consumers, and the drug firm with attendant factors, including those that are technical, legal, economic, demographic, political, social, ecological, and infrastructural. Since drug research can be a high-risk, high-payoff industry, it is important to researchers to effectively and strategically manage the drug discovery process. This book takes a closer look at increasing pre-approval costs for new drugs and examines not only why these increases occur, but also how they can be overcome to ensure a robust pharmacoeconomic future. Written in an engaging manner and including memorable insights, this book is aimed at redirecting the drug discovery process to make it more efficient and cost-effective in order to achieve the goal of saving countless more lives through science. A valuable and compelling resource, this is a must-read for all students and researchers in academia and the pharmaceutical industry.

Obesity has reached epidemic proportions globally and presents a major challenge to policy makers and clinicians alike. Recent research has suggested that obesity has its origins in early life and that early diet can programme a developing fetus and young infant s future susceptibility to obesity. This volume contains recent findings presented at the International Conference on Early Nutrition Programming and Health Outcomes in Later Life: Obesity and Beyond - a satellite meeting of the 15th European Congress on Obesity, held in Budapest in April 2007. Basic scientific research, data from epidemiological studies and clinical trial results were all presented during the programme.

This volume includes articles discussing the evidence for an effect of early nutrition programming on later obesity and cardiovascular risk; the growing evidence for an intergenerational cycle of obesity; the role of maternal leptin in programming appetite; possible cellular mechanisms for altered energy balance, including mitochondrial programming and the effects of regulators of metabolism; and how epigenetic changes might be the fundamental underlying mechanism explaining programming effects. Consumer understanding of the concept of early nutrition programming and the extent to which early nutrition programming is taken into account in infant feeding policies are also discussed.

This book presents a systematic survey of different local treatments in inflammatory joint diseases and their potential side effects and complications. Both surgical therapies and pharmaceutical strategies involving local or systemic application of anti-inflammatory and immunomodulating drugs are addressed. Special emphasis is placed on nuclear medicine therapy by intra-articular instillation of beta radiation emitters, known as radiosynoviorthesis or radiation synovectomy. Possible complications, in particular radionecrosis, infection, and thromboembolism, are described and available treatment strategies are examined in detail. In addition, radiation safety considerations are critically reviewed and relevant clinical questions are discussed. While radiosynoviorthesis is an effective and safe treatment if a proper indication is secured and if the application is performed by an experienced nuclear medicine physician, local complications can never be excluded with certainty. This book will support physicians who are engaged in the care and treatment of patients with inflammatory joint disease, approximately 30,000 of whom undergo radiosynoviorthesis in Europe each year.

Currently, there are tremendous advances being made in understanding the basic science of both the structure and function of botulinum neurotoxins. This knowledge is opening up opportunities in regard to both therapeutic uses and treatment and protection options for civil and bio-defense applications. This volume fully evaluates the status of neurotoxin research and exploitation with a focus on clinical application. The book is a multi-authored collection of chapters written by the leading authorities responsible for the current scientific and clinical research that is advancing the understanding and exploitation of the neurotoxins and is both up to date and authoritative.

Increased knowledge on the pathogenesis of hematologic diseases has been translated into diagnostic and prognostic applications. Hematopathology and laboratory hematology were among the first disciplines to embrace molecular diagnostics. Hematological Malignancies:Methods and Protocols, explores molecular-based assays frequently used in the routine diagnostic hematopathology and laboratory hematology. Many of these protocols were initially developed as research applications and were further refined as they transitioned to the diagnostic laboratory. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Hematological Malignancies: Methods and Protocols aids scientist in the continuing study of tests essential for contemporary laboratory diagnostics of hematological neoplasms.

Apoptosis: Involvement of Oxidative Stress and Intracellular Ca2+ Homeostasis, presents a concise synthesis of the current knowledge and recent advances in the mechanisms of apoptosis in different cells and the role of oxidative stress and Ca2+ signalling. Particular attention is given to the different features of apoptosis in distinct cell types, ranging from hepatocytes to cardiovascular and blood cells, nervous cells or spermatozoa.

Cutting-edge and user-friendly, this volume serves as a comprehensive resource for those interested in the fascinating biological processes associated to programmed cell death or apoptosis. The book is divided in two major chapter sections: general mechanisms of the apoptotic pathways and the role of oxidative stress and intracellular Ca2+ homeostasis and a more specific section dedicated to the specificities of apoptosis in a number of excitable and non-excitable cells.

All of the contributions are from specialists in the field and the reviews presented, systemically examine the most exciting and innovative aspects of the apoptotic pathways in their particular areas of expertise.

This book introduces the reader to drug delivery with specific emphasis on the use of nanoparticles. It covers properties, characterization, and preparation of different types of nanoparticles and discusses recent advances in their structural design and biomedical application, as well as the issues and challenges associated with their design and use. Some of the topics covered include the potential application of nanoparticles in biomedical fields, hazards associated with use of nanoparticles for drug delivery, size-dependent factors in drug delivery applications, different organic, inorganic and their hybrid systems used in drug delivery, etc. It also highlights use of nanoparticles in controlled and targeted drug delivery, and their application in stimuli-responsive, especially pH-responsive, drug release. Additionally, it also focuses on biomimetic nanoparticles, challenges faced in the designing of nanoparticles for drug delivery in cancer, viral and bacterial diseases. The contents of this volume will be useful to researchers and professionals working on advances in targeted drug delivery systems.

Store-operated Ca2+ entry (SOCE) serves to control essential functions throughout the human body and represents a novel and attractive target for therapeutic intervention. This book provides an extensive overview of the role of SOCE pathways in Molecular Physiology and Cell Biology, as well as their clinical significance. (Patho)physiological principles and emerging therapeutic strategies are delineated in a way that is valuable both for the education of graduate students in advanced Cell Biology/Molecular Physiology and for the promotion of innovative research and developments in the clinical/therapeutic fields. A comprehensive, clear and elaborate representation of current concepts is provided, including a pathophysiological section arranged in a tissue/organ/system-oriented manner. The book is intended for basic researchers specializing in cell signaling, ion transport, or pharmacology, as well as biomedical scientists and clinicians with a focus on immunology, neurology or cardiology.

This volume illustrates the functional properties of NAbs. Authors from pioneering groups report in their chapters on the tissue homeostatic, tissue regenerating and regulatory properties of NAbs and NAbs in pooled human IgG. Scientists interested in the regulation and modulation of components of the immune system found a whole variety of NAbs to cytokines with regulatory and protective functions and NAbs that modulate, e.g., dendritic cells, regulatory T cells, B cells and granulocytes. Considering the large plasma pools and initial difficulties in preparing IVIG that does not induce adverse effects upon infusion into recipients, this volume ends with a historical chapter on how pooled human plasma was fractionated and the IgG component pretreated for a safe intravenous application.

The advancements of medical technology, improvements in medical care, and increased patients' life span make pain research and related drug development high priorities for both the research community and pharmaceutical companies. Rapid development of basic science research tools, such as techniques of flurometric labeling, genomic and proteomic high throughput screening, and genetically modified animals, promotes the swift acceleration of pain research to a stage allowing integrated investigations of pain processing mechanisms at the single cell and/or molecule level, and in a spatially and temporally controlled manner. Using multidisciplinary approaches, we can dissect the complicity of the sensory circuits connecting peripheral stimulation to maladaptive changes in the sensory pathways as well as pain perceptions at the central nervous system. Pain Research: Methods and Protocols, Second Edition provides advanced techniques and animal models that are critical for integrated pain research. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and accessible, Pain Research: Methods and Protocols, Second Edition serves as an ideal guide to novice pain researchers who may not have extensive experiences in the field, or to experienced pain researchers who would like to expand their research in new directions and/or to new mechanisms in different models.

Principles of Research Methodology: A Guide for Clinical Investigators is the definitive, comprehensive guide to understanding and performing clinical research. Designed for medical students, physicians, basic scientists involved in translational research, and other health professionals, this indispensable reference also addresses the unique challenges and demands of clinical research and offers clear guidance in becoming a more successful member of a medical research team and critical reader of the medical research literature. The book covers the entire research process, beginning with the conception of the research problem to publication of findings. Principles of Research Methodology: A Guide for Clinical Investigators comprehensively and concisely presents concepts in a manner that is relevant and engaging to read. The text combines theory and practical application to familiarize the reader with the logic of research design and hypothesis construction, the importance of research planning, the ethical basis of human subjects research, the basics of writing a clinical research protocol and scientific paper, the logic and techniques of data generation and management, and the fundamentals and implications of various sampling techniques and alternative statistical methodologies. Organized in thirteen easy to read chapters, the text emphasizes the importance of clearly-defined research questions and well-constructed hypothesis (reinforced throughout the various chapters) for informing methods and in guiding data interpretation. Written by prominent medical scientists and methodologists who have extensive personal experience in biomedical investigation and in teaching key aspects of research methodology to medical students, physicians and other health professionals, the authors expertly integrate theory with examples and employ language that is clear and useful for a general medical audience. A major contribution to the methodology literature, Principles of Research Methodology: A Guide for Clinical Investigators is an authoritative resource for all individuals who perform research, plan to perform it, or wish to understand it better.

This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.

This book provides the first comprehensive overview of a new scientific discipline termed Geroscience. Geroscience examines the molecular and cellular mechanisms that might explain why aging is the main risk factor for most chronic diseases affecting the elderly population. Over the past few decades, researchers have made impressive progress in understanding the genetics, biology and physiology of aging. This book presents vital research that can help readers to better understand how aging is a critical malleable risk factor in most chronic diseases, which, in turn, could lead to interventions that can help increase a healthy lifespan, or 'healthspan.' The book begins with an analysis of the Geroscience hypothesis, as well as the epidemiological underpinnings that define aging as a candidate main risk factor for most chronic diseases. Next, each chapter focuses on one particular disease, or group of diseases, with an emphasis on how basic molecular and cellular biology might explain why aging is a major risk factor for it. Coverage in the book includes: cancer, cardiovascular disease, dementias, stroke, Parkinson's and Alzheimer's diseases, osteoporosis, arthritis, diabetes asthma, emphysema, kidney disease, vision impairment, and AIDS/HIV. It finishes with a chapter on pain in the elderly and an overview of future steps needed to bring the newly acquired knowledge into the clinic and the public at large.

This book presents the timeline of immunodiagnostics evolution, including advancements in immunological/nucleic acid probes, assay design, labelling techniques, and devices for signal transduction and acquisition. In the past few years, enzyme and nanocatalyst-based immune assays have undergone numerous modifications to enhance their sensitivity and potential for automation. Further, to reduce production costs and the use of laboratory animals, engineering small antibodies and nucleic acid probes (aptamers) has become increasingly popular in the development of novel and powerful bioassays. In light of the notable advancements in immunodiagnostics, this book highlights the combined efforts of clinicians, biotechnologists, material scientists, nanotechnologists and basic scientists in a coherent and highly structured way. The book takes readers on the journey of immunodiagnostic technologies, from their introduction to the present.

Although phosphorylation of proteins on tyrosine is relatively rare compared to phosphorylation on serine or threonine residues, the past two decades of research into PTP function have led to a great appreciation of the critical role PTPs have in regulating basic cellular processes. Among these important roles is the regulation of cellular signaling pathways related to metabolism. This volume contains chapters which highlight many aspects of PTP function in the context of metabolism. Given the growing obesity and diabetes epidemics in the United States and throughout the world, the desire to identify possible therapeutic targets for treatment of these diseases is a high priority. In many ways, PTPs may be attractive drug targets since they are amenable to targeting with small molecules; however many challenges abound in making PTP inhibitors.

This third edition of the classic "how-to" guide incorporates recent changes in policies and procedures of the NIH, with particular emphasis on the role of the Internet in the research proposal process. Completely revised and updated, it reveals the secrets of success used by seasoned investigators, and directs the reader through the maze of NIH bureaucracies. In addition to providing a detailed overview of the entire review process, the book also includes hundreds of tips on how to enhance proposals, excerpts from real proposals, and extensive Internet references. This book is essential to all scientists involved in the grant writing process.
Key Features:
* Considers the reviewer's perspective
* Detailed presentation of the review process
* All sections of the R01 proposal are reviewed
* Hundreds of tips to enhance proposals
* Includes the many recent changes in NIH policies
* Includes many excerpts from real proposals
* Provides extensive Internet references
Benefits:
* Increased competitiveness
* Better priority scores
* Less chance of triage
* Increased award rates
* Uses the system to advantage
* Reveals strategies used by the "old pros"

This book contains a wealth of practical guidance about what doing research actually involves for the often hard-pressed and isolated researcher. It bridges the gap and provides 'real-life' insight into undertaking research in nursing. It focuses on the practicality of research and identifies the pitfalls that can so easily undermine even the most carefully planned project.Practical check lists Case studies Latest information on searching on the Web Include good clinical practice for ethical research - to educate nurses on research - so that they will speak up for patients. Latest information on R & D strategy in the NHS The chapter on a career in research will be expanded and given priority.

This book highlights electromagnetic actuation (EMA) and sensing systems for a broad range of applications including targeted drug delivery, drug-release-rate control, catheterization, intravitreal needleless injections, wireless magnetic capsule endoscopy, and micromanipulations. It also reviews the state-of-the-art magnetic actuation and sensing technologies with remotely controlled targets used in biomedicine.

Although cell fusion is an omnipresent process in life, to date considerably less is still known about the mechanisms and the molecules being involved in this biological phenomenon in higher organisms. In Cell Fusion in Health and Disease Vol 1 & Vol 2 leading experts will present up-to-date overviews about cell fusion in physiological and patho-physiological processes, which further covers the current knowledge about cell fusion-mediating molecules. Volume 1 deals with Cell Fusion in Health and will cover aspects of cell fusion in fertilization, placentation, in C. elegans, in skeletal muscle development and tissue repair, and the use of cell fusion for cellular reprogramming and cancer vaccine development. Volume 2 focuses on Cell Fusion in Disease with a particular emphasis on the role of cell fusion in cancer development and progression. Thus, Cell Fusion in Health and Disease Vol 1 & Vol 2 represents a state-of-the-art work for researchers, physicians or professionals being interested in the biological phenomenon of cell fusion and beyond.