The book focuses on the aqueous interface of biomolecules, a vital yet overlooked area of biophysical research. Most biological phenomena cannot be fully understood at the molecular level without considering interfacial behavior. The author presents conceptual advances in molecular biophysics that herald the advent of a new discipline, epistructural biology, centered on the interactions of water and bio molecular structures across the interface. The author introduces powerful theoretical and computational resources in order to address fundamental topics such as protein folding, the physico-chemical basis of enzyme catalysis and protein associations. On the basis of this information, a multi-disciplinary approach is used to engineer therapeutic drugs and to allow substantive advances in targeted molecular medicine. This book will be of interest to scientists, students and practitioners in the fields of chemistry, biophysics and biomedical engineering.

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.

Accelerated Path to Cures provides a transformative perspective on the power of combining advanced computational technologies, modeling, bioinformatics and machine learning approaches with nonclinical and clinical experimentation to accelerate drug development. This book discusses the application of advanced modeling technologies, from target identification and validation to nonclinical studies in animals to Phase 1-3 human clinical trials and post-approval monitoring, as alternative models of drug development. As a case of successful integration of computational modeling and drug development, we discuss the development of oral small molecule therapeutics for inflammatory bowel disease, from the application of docking studies to screening new chemical entities to the development of next-generation in silico human clinical trials from large-scale clinical data. Additionally, this book illustrates how modeling techniques, machine learning, and informatics can be utilized effectively at each stage of drug development to advance the progress towards predictive, preventive, personalized, precision medicine, and thus provide a successful framework for Path to Cures.

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 introduces a new cyberphysical system that combines clinical and basic neuroscience research with advanced data analysis and medical management tools for developing novel applications for the management of epilepsy. The authors describe the algorithms and architectures needed to provide ambulatory, diagnostic and long-term monitoring services, through multi parametric data collection. Readers will see how to achieve in-hospital quality standards, addressing conventional "routine" clinic-based service purposes, at reduced cost, enhanced capability and increased geographical availability. The cyberphysical system described in this book is flexible, can be optimized for each patient and is demonstrated in several case studies.

This book explores Dental Stem Cell (DSC) biology, from a review of basic concepts for cell culture, to isolation, self-renewal, multipotency and differentiation, regulation by molecular medicine, and prospective research areas for regenerative medicine. The first seven chapters delve into basic DSC properties, vital signaling pathways involved in differentiation, pluripotency, iPS cell development from DSCs, and genetic engineering approaches of DSCs in accordance with the current literature. A comprehensive review of possible clinical applications and in vitro/in vivo studies follows, illustrating the future of DSC research for in the tissue engineering field. The text also discusses the political, ethical, social, and legal ramifications of the use of dental stem cells. Expertly authored and drawing from a multitude of international perspectives, Dental Stem Cells is an invaluable addition to Springer's Stem Cell Biology and Regenerative Medicine series. It is essential reading for advanced graduate students, basic researchers, and clinical investigators in the fields of stem cell therapy, biological sciences of dentistry, and regenerative medicine.

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.

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.

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 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.

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.

From bandage to the bioreactor, this book looks at five different device technologies from inception to healthcare practice, drawing on medical sociology, science and technology studies and political science. It examines "evidence," regulation and governance processes, and diverse stakeholders in innovating the technologies that shape health care.

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.

How to identify optimal phase II trial designs Providing a practical guide containing the information needed to make crucial decisions regarding phase II trial designs, A Practical Guide to Designing Phase II Trials in Oncology sets forth specific points for consideration between the statistician and clinician when designing a phase II trial, including issues such as how the treatment works, choice of outcome measure and randomization, and considering both academic and industry perspectives. A comprehensive and systematic library of available phase II trial designs is included, saving time otherwise spent considering multiple manuscripts, and real-life practical examples of using this approach to design phase II trials in cancer are given. A Practical Guide to Designing Phase II Trials in Oncology: * Offers a structured and practical approach to phase II trial design. * Considers trial design from both an academic and industry perspective. * Includes a structured library of available phase II trial designs. * Is relevant to both clinical and statistical researchers at all levels * Includes real life examples of applying this approach. * For those new to trial design, A Practical Guide to Designing Phase II Trials in Oncology will be a unique and practical learning tool, providing an introduction to the concepts behind informed decision making in phase II trials. For more experienced practitioners, the book will offer an overview of new, less familiar approaches to phase II trial design, providing alternative options to those which they may have previously used.

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.

Phototherapy exemplifies scientific medicine. The major advances have resulted from effective collaborations between basic researchers and clinicians. This book is directed to clinicians and basic researchers who are interested in current and emerging implementations of phototherapy. It can serve as an introductory reference and a textbook for advanced undergraduate and graduate courses in medical physics and biomedical engineering. The emphasis is on the science underlying the various phototherapy procedures, which encompasses aspects of classical and molecular photophysics, biological photochemistry, photobiology and biophotonics. Topics that do not usually appear in other general sources include the theory and applications of tissue optics, Monte Carlo simulation, light dosimetry, and analytical modeling of laser surgery. Many illustrative problems with answers are provided to exemplify the more quantitative aspects of each topic.

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.

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 book highlights the responsibility of medical device designers and engineers to eliminate sites of failure and to test devices to demonstrate their ultimate safety and efficacy. It also evaluates biomaterials and their properties as related to the design and reliability of medical devices. The principles that are described are readily applicable to the biomaterial scaffolds used for generating tissue-engineered constructs.

Analytical chemists and materials scientists will find this a useful addition to their armory. The contributors have sought to highlight the present state of affairs in the validation and quality assurance of fluorescence measurements, as well as the need for future standards. Methods included range from steady-state fluorometry and microfluorometry, microscopy, and micro-array technology, to time-resolved fluorescence and fluorescence depolarization imaging techniques.

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 covers the molecular and cellular aspects of cancer metastasis, and discusses the clinical aspect of micro- and macro-metastases, which result in the death of the majority of patients with cancer. The current edition attempts to examine the current status of the basic scientific and clinical research in the area, and is a very useful reference for clinicians, oncologists, and biologists. It is intended for undergraduates as well as postgraduates in the area of medicine, oncology, and cancer biology.