This book comprises protocols describing systems biology methodologies and computational tools, offering a variety of ways to analyze different types of high-throughput cancer data. Chapters give an overview over data types available in large-scale data repositories and state-of-the-art methods used in the field of cancer systems biology. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Cancer Systems Biology : Methods and Protocols aims to ensure successful results in the further study of this vital field. The chapters "Identifying Genetic Dependencies in Cancer by Analyzing siRNA Screens in Tumor Cell Line Panels", "Perseus: A Bioinformatics Platform for Integrative Analysis of Proteomics Data in Cancer Research" and "Phosphoproteomics-based Profiling of Kinase Activities in Cancer Cells" are available open access under a CC BY 4.0 license via link.springer.com.

Biomedical research is increasingly carried out in low- and middle-income countries. International consensus has largely been achieved around the importance of valid consent and protecting research participants from harm. But what are the responsibilities of researchers and funders to share the benefits of their research with research participants and their communities? After setting out the legal, ethical and conceptual frameworks for benefit sharing, this collection analyses seven historical cases to identify the ethical and policy challenges that arise in relation to benefit sharing. A series of recommendations address possible ways forward to achieve justice for research participants in low- and middle-income countries.

"This book uses Caenorhabditis elegans as model animal to introduce the toxicity induction of toxicants at environmentally relevant concentrations under different conditions. It also discusses the systematic introduction of different molecular signaling pathways, as well as G protein coupled receptors and ion channels, in regulating the toxicity of toxicants at environmentally relevant concentrations. The intestinal, neuronal, and germline molecular networks required for the regulation of toxicity of toxicants at environmentally relevant concentrations is further introduced and discussed. This book aims at providing a systematic understanding of the knowledge system on toxicology at environmentally relevant concentrations in Caenorhabditis elegans. "

This book gathers multidisciplinary articles that present advances of our understanding of diseases and the effective treatment of patients. The authors share recent clinical and experimental research findings, highlighting poorly understood areas with uncertain treatment outcomes, such as giant-cell bone tumors and their propensity to metastasize to the lungs; subterranean rehabilitation in pulmonary disorders; male reproductive hormone regulation during physical exercise in hyperbaric, hyperoxic environments, like underwater diving; and amelioration of cognitive decline owing to increased cerebral blood transit time after internal carotid artery stenting. Other topics include new concepts and innovations in the treatment of diabetes in pregnancy, and leg ulcers in chronic venous insufficiency, as well as molecular research on the toxic effects of oxidative stress, impaired cell autophagy, and experimental conditions resembling air pollution. Featuring the latest interdisciplinary advances in biomedicine, this book is a valuable resource for medical professionals, both academics and practitioners, and all allied health-care workers.

In Wound Regeneration and Repair: Methods and Protocols, expert researchers in the field detail classical and cutting-edge methods for studying wound healing and regeneration. These techniques include cellular and molecular methods, genetic approaches, surgical procedures, clinical advances, drug discovery and delivery modalities, animal and humanized models and new applications in the treatment of pathological wounds in a variety of organs and tissues. Written in the highly successful Methods in Molecular Biology series format, chapters include an introduction to their respective topics, a detailed list of the necessary materials and reagents for each procedure, step-by-step, reproducible laboratory protocols, and a set notes, developed by the authors, for troubleshooting and avoiding known pitfalls. Authoritative and practical, Wound Regeneration and Repair: Methods and Protocols seeks to aid scientists and entrepreneurs in their further study of technologies, models, techniques, and critical new areas and approaches to clinical and commercial translation of research.

Leading scientists summarize the latest findings on signal transduction and cell cycle regulation and describe the effort to design and synthesize inhibiting molecules, as well as to evaluate their biochemical and biological activities. They review the relevant cell surface receptors, their ligands, and their downstream pathways. Also examined are the latest findings on the components of novel signaling networks controlling the activity of nuclear transcription factors and cell cycle regulatory molecules. Cutting-edge and highly suggestive, Signaling Networks and Cell Cycle Control: The Molecular Basis of Cancer and Other Diseases presents a wealth of information on the emerging principles of the field, as well as an invaluable guide for all experimental and clinical investigators of cell regulation and its rapidly emerging pharmacological opportunities today.

A must-have guide for any professional in the drug manufacturing industry

The Good Clinical Practice (GCP) audit is a tedious but necessary exercise that assures that all parties do their job properly and in compliance with the applicable FDA code. "Clinical Trials Audit Preparation" demystifies the audit process for all parties involved, including clinical research sponsors, clinical investigators, and institutional review boards.

This book provides a step-by-step explanation of the FDA audit procedures for clinical trials and of how pharmaceutical companies, clinical investigators, and institutional review boards should prepare for regulatory audits. The book emphasizes the processes and procedures that should be implemented before a clinical audit occurs, making this an imperative guide to any professional in the drug manufacturing industry, including drug manufacturing companies, regulatory affairs personnel, clinical investigators, and quality assurance professionals.

Among the topics discussed:

Good Clinical Practices and therapeutic product development in clinical research

The roles of the sponsor of a clinical investigation, the IRB, or independent ethics committee

The roles and responsibilities of the clinical trial investigator

The inspection preparation

The Audit Report and the Form 483

Warning letters issued to clinical investigators and clinical trial sponsors and their impact on product development

The truth is, few people know the first thing about clinical research. The public reads about a medical research project that announces unbelievable results for a miraculous drug. Some years later, another investigation completely wipes out those initial favorable findings. Hormones Cut Women's Risk of Heart Disease (San Francisco Chronicle, 1994) Hormones Don't Protect Women from Heart Disease, Study Says (Washington Post, 2001) The people are confused because we do not understand the process behind these conflicting results. Our health, and in fact, our very lives are dependent on clinical trials, but we know little about them. This book explains the issues the public needs to be aware of when it comes to clinical research. It uncovers the problems in medical investigations that can not be overcome no matter how much care and diligence medical researchers bring to a research project. The basic premise that drives the writing is that it is impossible for medical researchers to guarantee that they can get all the right answers from a single study. No matter how good the investigators are, no matter how well a study is planned, no matter how carefully the plans are executed and no matter how conscientiously the results are analyzed and interpreted - the answer may still be wrong. The deck is stacked against medical researchers and the public - you - should be skeptical of the results no matter how impressive they seem on the surface.

This book systemically presents the latest research on renal fibrosis, covering all the major topics in the field, including the possible mechanisms, biomarkers, and strategies for prevention and treatment of chronic kidney disease (CKD). Due to its high prevalence, CKD represents a huge global economic and social burden. Irrespective of the initial causes, CKD progresses to end stage kidney disease (ESKD) due to renal fibrosis, which is characterized by glomerulosclerosis, tubule atrophy and atresia, and the excessive accumulation of extracellular matrix (ECM) in the kidney. Unfortunately, an estimated 1%-2% of the adult population living with CKD will need renal replacement therapy at some point as a result of ESKD. As such, strategies for preventing or slowing CKD progression to ESKD are of utmost importance, and studies aiming to understand the mechanisms of renal fibrosis have been the focus of intensive research. Recently, novel insights into the pathophysiological processes have furthered our understanding of the pathogenesis of renal fibrosis, and more importantly, promoted studies on the early diagnosis and treatment of CKD. This book draws lessons from the extensive, state-of-the-art research in this field, elaborating the new theories and new techniques to offer readers a detailed and comprehensive understanding of renal fibrosis and as well as inspiration for future research directions.

The study of molecular events leading to cellular transformation and cancer has progressed considerably during the 1990s. It has become apparent that many genes subject to modification in cancer are, in fact, transcription factors that govern the execution of the genetic programme of the cell. Transcription factors can behave either as oncogenes or as tumor supressor genes. To date only a very limited number of transcription factors have been associated with cancer. This volume gives molecular information on several oncogenes, tumor suppressor genes or chromosomal translocations. Each chapter contains a description of the structure of such transcription factors, the nature of target genes, the regulation of their activities and an explaination of how they can deregulate cell growth and differentiation. This book should be suitable for the specialist scientist and the advanced student

The volume is comprehensively covers emerging technologies for health care, various aspects of biomedical research towards understanding of pathophysiology of the diseases, advances in improvement in diagnostic procedures and therapeutic tools, the fundamental role of biomedical research in the development of new medicinal products

Since the very early stages of life, we all experience some form of stress. Stressors can be mild to severe and can range from unsuccessfully longing for maternal milk in infancy, to recklessly wiggling on a motorbike to be on time to watch the NBA finals on TV, to breaking up a relationship. All those events that we call "stress" have the capability of perturbing a given state of psychological and physiological equilibrium and moving it to a different level. The transition from crawling to walking has to be considered a form of stress as much as losing a job. It is through a continuous cross-talk between environmental stressors and individual adaptations that we build our personalities and our ways to cope with daily hassles. External challenges should not necessarily be regarded as "bad", but instead seen as constructive forces forming our ability to navigate a changing world. What is stress good for? What is stress bad for? When and why do we need to be "stressed"? Should we worry about stress? When does stress equate to "normality"? When does it turn into pathology? We hope with this book to provide some answers to these fundamental questions.

With the advent of new technologies in big data science, the study of medical problems has made significant progress. Connecting medical studies and computational methods is crucial for the advancement of the medical industry. Big Data Analytics in HIV/AIDS Research provides emerging research on the development and implementation of computational techniques in big data analysis for biological and medical practices. While highlighting topics such as deep learning, management software, and molecular modeling, this publication explores the various applications of data analysis in clinical decision making. This book is a vital resource for medical practitioners, nurses, scientists, researchers, and students seeking current research on the connections between data analytics in the field of medicine.

Rabies is the deadliest zoonotic disease that threatens humans and animals on all continents except Antarctica. Asia and Africa are worst affected as more than 95 per cent of rabies associated human deaths occur in these regions. India alone bears about 36 per cent of the global human rabies burden. Dogs are the main transmitters of rabies that potentially threaten over 3 billion people in Asia and Africa. Many developed nations have been able to successfully control dog rabies but continue to face the risk from wildlife including bats. Bat rabies is responsible for most human rabies deaths in the United States of America and Canada but has emerged as a public health threat in Australia, Latin America and Western Europe as well. Despite being vaccine preventable, rabies continues to haunt the mankind. Poor resources is a major constraint but the factors like low priority attributed to rabies, misconceptions in the community about the disease and unsystematic approach for its prevention and control are also responsible for the grim situation. Targets have been set for elimination of human and dog rabies in all Latin American countries by 2015 and of human rabies transmitted by dogs in South-East Asia by 2020. However, the myths prevailing among the people together with inadequate knowledge of the health professionals, veterinarians, and the civic body staff about the rabies prevention and control strategies might make the task very difficult. This book comprising eight chapters elaborates the causation of rabies in man and animals, its global epidemiology, risk analysis and effective strategies for the management of exposures. Proven methods of rabies prevention and control have been discussed in length along with the challenges and ways to overcome the constraints through intersectoral coordination. The inclusion of 200 frequently asked questions is a unique feature of the book which may help not only the common people and pet lovers in clearing their doubts about rabies in man and animals also be equally instrumental in updating the knowledge and skills of the public health personnel, veterinarians and other professionals. Apt illustrations and simple language make the contents of the book easily comprehensible and a reading pleasure.

This volume describes important methods, protocols, and techniques used for studying urinary biomarkers. Chapters detail different alterations use to studied different types of cancers and physiological conditions. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Urinary Biomarkers: Methods and Protocols aims to be a useful practical guide to researches to help further their study in this field.

Pregnancy and the Pharmaceutical Industry: The Movement towards Evidence-Based Care for Pregnant Women explores the issues surrounding the decision to undertake clinical trials with pregnant women. There is currently a lack of data on the safety and effectiveness of medications used during pregnancy as it is impossible to extrapolate that information from drug studies on men and non-pregnant women. As a majority of pregnant women confront a medical condition during their pregnancy, from simple pain, to ongoing or new medical issues, this book quantifies the current absence of pregnant women in drug studies and identifies ethical issues, barriers, litigation fears and opportunities. Those in the pharmaceutical industry, IRB members who approve or deny drug study plans, doctors, nurses and midwives working in obstetrics or involved in conducting studies at their institutions will find this book an essential resource.

The ubiquitin system has two major functions in eukaryotic cells: it r- ulates protein degradation, which is essential for normal cellular fu- tion and for the removal of potentially harmful, damaged, or misfolded proteins, and it controls protein activity by regulating protein-protein interactions and subcellullar localization. The ubiquitin system is thus involved in processes as diverse as cell cycle progression, signal tra- duction, gene transcription, and DNA repair. Not surprisingly, defects in the ubiquitin system have been linked with numerous diseases such as cancer, in?ammation, central nervous system disorders, and metabolic dysfunction. Ubiquitin is a highly conserved 76-amino acid protein which is transferred to its target protein in an ATP-dependent manner. This post-translational modi?cation takes place in a hierarchical, three-step fashion involving an E1 ubiquitin-activating enzyme, an E2 ubiquit- conjugating enzyme, and an E3 ubiquitin ligase. Substrate speci?city is predominantly controlled by members of a large family of E3 - zymes, which form complexes with the proteins that will be modi?ed. This ultimately leads to the covalent attachment of the C-terminus of ubiquitin to usually an?-amino group of a lysine residue in the targeted protein. Additional ubiquitin transfer to lysine-48 of ubiquitin itself will form a polyubiquitin chain, which usually targets the conjugate for degradation by the proteasome. By contrast, mono- or polyubiquityla- VI Preface tion involving lysine-63 is normally involved in the control of protein activity. Ubiquitylation can be reverted by deubiquitylating enzymes, of which approximately 95 exist in mammals.

This volume provides in-depth descriptions and discussion of clinical trial designs based on novel data analysis of high-quality trials for 11 different neurological conditions in order to ultimately improve the quality of care in neurology. Some of the conditions discussed in this book are stroke, traumatic brain injury, Alzheimer's disease, epilepsy, and tumors of the central nervous system. In Neuromethods series style, chapters include the kind of detail and key advice from the specialists needed to get successful results in your research center and clinical investigation. Thorough and comprehensive, Clinical Trials in Neurology is a valuable guide for individuals in the research, education, and clinical practice fields, specifically in the fields of medicine, physical therapy, occupational therapy, nursing, and public health. This volume is also an important resource for clinicians aiming to improve their understanding in methodology of clinical trials.

This handbook provides an in-depth review of information across the developmental spectrum of gene and cell therapy products. From introductory information to state-of-the-art technologies and concepts, the book provides insights into upstream processes such as vector design and construction, purification, formulation and fill/finish as well as delivery options. Planning steps for compliance with current good manufacturing practice (CGMP) to readiness for chemistry, manufacturing, and controls (CMC) are also discussed.This book wraps up with examples of successes and pitfalls addressed by experts who have navigated the multiple challenges that are part of any innovative endeavor. Features Intended as a one-stop resource for availability of state-of-the-art information related to cell and gene therapy products for researchers, scientists, management and other academic and research institutions. Provides the most up to date information on the development of gene therapy, from the technology involved to gene correction and genome editing. Discusses siRNA, mRNA, and plasmid manufacturing. Describes the importance of supplier-sponsor synergies on the path to commercialization. Diverse audience with a large number of individuals in the core technologies and supportive practices.

Hundreds of eponyms are used within the field of immunology-Petri dish, Crohn's disease, Bence Jones protein, Kupffer cells, Freund's adjuvant, Ouchterlony immunodiffusion, to name just a few-but most of us don't know much about the individuals who gave their names to these terms. Where were they born and educated, what other accomplishments are they credited with, why has history chosen to remember them, or not? This book presents the first comprehensive collection of immunologic eponyms, and through them tells the story of this fascinating field, from its earliest beginnings to present day. Organized by surname and meticulously cross-referenced and indexed, this book offers historical anecdotes and little-known facts which scientists, clinicians, students, and general readers will find captivating and memorable. A one-of-a-kind introduction to immunology that serves as both a history lesson and current reference on the diseases, treatments, and individuals who have been crucial to this field.

Key Features: 1. Describes the development of the randomized, controlled trial as the gold standard of proof. 2. Unravels the meaning of "randomized," "double-blind" and "p-values" in a simplified manner for students and clinicians. 3. Contains timeless information on how medical evidence can be understood.

The volume is comprehensively covers emerging technologies for health care, various aspects of biomedical research towards understanding of pathophysiology of the diseases, advances in improvement in diagnostic procedures and therapeutic tools, the fundamental role of biomedical research in the development of new medicinal products

"Heart Failure: From Research to Clinical Practice" contains chapters that describe the current views on the biological mechanisms, clinical assessment, diagnosis and evidence-based treatments of the condition. Topics in this volume range from basic research at cell and molecular level to patient care in everyday clinical practice and provide essential background information and analyses of recent advances for a deeper understanding of the issues involved. With contributions from international experts in their specified fields and are suitable for both beginners and more advanced readers. This volume includes not only the essential information for clinical practice but also the latest information from the contemporary guidelines and the recommendations from leading societies. It also covers ongoing research and puts forward new hypotheses that can be tested in future research. This comprehensive volume will provide a valuable resource for both research students and expert clinicians.

Real-world evidence (RWE) has been at the forefront of pharmaceutical innovations. It plays an important role in transforming drug development from a process aimed at meeting regulatory expectations to an operating model that leverages data from disparate sources to aid business, regulatory, and healthcare decision making. Despite its many benefits, there is no single book systematically covering the latest development in the field. Written specifically for pharmaceutical practitioners, Real-World Evidence in Drug Development and Evaluation, presents a wide range of RWE applications throughout the lifecycle of drug product development. With contributions from experienced researchers in the pharmaceutical industry, the book discusses at length RWE opportunities, challenges, and solutions. Features Provides the first book and a single source of information on RWE in drug development Covers a broad array of topics on outcomes- and value-based RWE assessments Demonstrates proper Bayesian application and causal inference for real-world data (RWD) Presents real-world use cases to illustrate the use of advanced analytics and statistical methods to generate insights Offers a balanced discussion of practical RWE issues at hand and technical solutions suitable for practitioners with limited data science expertise

This book, which is the third volume of Biomedical translational research, focuses on the fundamental role of biomedical research in developing new medicinal products. It emphasizes the importance of understanding biological and pathophysiological mechanisms underlying the disease to discover and develop new biological agents. The book uniquely explores the genomic computational integrative approach for drug repositioning. Further, it discusses the health benefits of nutraceuticals and their application in human diseases. Further, the book comprehensively reviews different computational approaches that employ GWAS data to guide drug repositioning. Finally, it summarizes the major challenges in drug development and the strategies for the rational design of the next generation more effective but less toxic therapeutic agents.