Unique and timely volume as mRNA is a hot area of research making great strides. Covers the full-scale production systems that are needed to develop vaccines as well as elements of data needed to secure the IND approvals. Introduces a commercial-scale manufacturing process using novel techniques like the PCR, in addition to the traditional plasmid DNA. First book that offers commercial technology for developing and large-scale supply of mRNA products. Renowned author and entrepreneur in the field of drug discovery and production.

Why do some people miraculously turn around after suffering from life threatening illnesses, emotional trauma, and spiritual despair?

Dr. Ronan Kisch has documented twenty-seven bodywork/massage therapists whose clients-despite grave medical prognoses or life trauma-had unusual, if not miraculous recoveries after having bodywork with these practitioners. Who are these practitioners that have had these successes? What transpired in their sessions that allowed for such miraculous events? What is it that you could do to create these possibilities for yourself and others? Dr. Kisch, who brought to light the psycho-behavioral aspects confronting bodywork practitioners in "Beyond Technique: The Hidden Dimensions of Bodywork, " now examines the spiritual domain of bodywork.

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.

In medical and health care the scientific method is little used, and statistical software programs are experienced as black box programs producing lots of p-values, but little answers to scientific questions. The pocket calculator analyses appears to be, particularly, appreciated, because they enable medical and health professionals and students for the first time to understand the scientific methods of statistical reasoning and hypothesis testing. So much so, that it can start something like a new dimension in their professional world. In addition, a number of statistical methods like power calculations and required sample size calculations can be performed more easily on a pocket calculator, than using a software program. Also, there are some specific advantages of the pocket calculator method. You better understand what you are doing. The pocket calculator works faster, because far less steps have to be taken, averages can be used. The current nonmathematical book is complementary to the nonmathematical "SPSS for Starters and 2nd Levelers" (Springer Heidelberg Germany 2015, from the same authors), and can very well be used as its daily companion.

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.

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.

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.

This volume describes the identification of emerging organic pollutants, mainly from industrial sources, their associated toxicological threats, and the latest green methods and biotechnological solutions to abate harmful impacts on people and the environment. The chapters present reviews on current applied toxicology research, occupational health hazards and green remedial solutions for pollution control in terrestrial and aquatic environments, with the aim of raising public awareness of these issues and providing chemists, toxicologists and environmental scientists with the knowledge to combat organic pollutants through sustainable means. Readers will learn about the multi-dimensional applications of materials and processes which harvest energy out of environmental remediation technologies, as well as the roles of biotechnology and nanotechnology in addressing high pollutant load. Specific attention is paid to technologies that draw energy through wastewater remediation, as this covers the primary means by which organic pollutants are introduced into the environment from industry and other sources. The book will be of use to pollution control boards, industry regulators, and students and researchers in the fields of biotechnology, biomedical science, hydrology and water chemistry.

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.

Precision Medicine in Neurodegenerative Disorders, Part One, Volume 192 deals with the "Why" in the approach to slow the progression of those suffering from diseases of accelerated brain aging. Matching a biology-correcting therapy with those biologically suitable to benefit from such therapy represents the vision and mission of precision medicine, the highest level of personalized medicine. This first Handbook of Clinical Neurology volume is intended to provide a scholarly background on the framework, basic science, and conceptual pitfalls related to disease-modifying efforts in Parkinson, Alzheimer, and other neurodegenerative disorders. Among the topics covered are the different models of precision medicine, the lumping-versus-splitting tension in biomarker development and therapeutics, and the rationale for replacing the convergence of the prevailing autopsy-based nosology of neurodegenerative diseases with the divergence of a systems biology approach to human diseases. Specific chapters are dedicated to the promise of genetic subtypes and the lessons in disease modification offered by the fields of oncology and cystic fibrosis that can be adapted to the field of neurodegeneration.

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.

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.

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.

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.

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.

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

This book aims to comprehensively review the current cell-based strategies under investigation to achieve the regeneration of human hair follicles. The unique capacity of the human hair follicle to self-renew explains why this complex "mini-organ" has always attracted so much interest as a model for researchers to study stem cell biology and regenerative medicine. The hair follicle is considered a main reservoir of cutaneous stem cells, containing several pools of epithelial, melanocyte, and mesenchymal stem cells involved in hair follicle self-regeneration and pigmentation. In addition, while some of the different follicular cell types contribute to hair shaft growth, others participate in very important interfollicular functions such as dermal remodeling, re-epithelialization after wounding, and cutaneous stem cell homeostasis. The idea of human hair follicle regeneration either "de novo" or by activating dormant miniaturized follicles is not new, yet still continues to arouse enormous interest in the pursuit of a definitive cure for baldness. In contrast to hair follicle regeneration in mice, the attempts made with human follicles have been disappointing in terms of efficiency. However, recent advances in stem cell biology-as well as the appearance of new technologies like 3D printing-have revived expectations in this field of research. This book is divided into four sections. The first part includes an overview of the strategies used in hair follicle regeneration and a historical summary of the most important achievements to date. Parts two and three comprise the main body of the book, with detailed descriptions of the cells and tissue structures involved in hair follicle regeneration, followed by an elaboration of the different therapeutic strategies, engineering techniques, and a clinician's perspective of stem cell-based therapies in hair loss treatments. Finally, the fourth part reviews the important contribution of the hair follicle in healing cutaneous wounds through the regeneration and remodeling of the dermis and epidermis after injury, as well as wound induced hair follicle neogenesis that occurs when the skin is injured.

"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.

Provides a comprehensive review of challenges and opportunities as related to the applications of big data, AI, and machine learning in the entire spectrum of drug R&D Discusses regulatory developments in leveraging big data and advanced analytics in drug review and approval Offers a balanced approach to data science organization build Presents real-world examples of AI-powered solutions to a host of issues in the lifecycle of drug development Affords sufficient context for each problem and provides detailed description of solutions suitable for practitioners with limited data science expertise

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.

Principles of Clinical Cancer Research provides comprehensive coverage of the fundamentals of clinical cancer research, including the full spectrum of methodologies used in the field. For those involved in research or considering research careers, this book offers a mix of practical advice and analytical tools for effective training in theoretical principles as well as specific, usable teaching examples. The clinical oncologist or trainee will find a high-yield, practical guide to the interpretation of the oncology literature and the application of data to real-world settings. Valuable for both researchers and clinicians who wish to sharpen their skills, this book contains all the cornerstones and explanation needed to produce and recognize quality clinical science in oncology.Written from the physician-scientist's perspective, it lays a strong foundation in pre-clinical sciences that is highly relevant to careers in translational oncology research along with coverage of population and outcomes research and clinical trials. It brings together fundamental principles in oncology with the statistical concepts one needs to know to design and interpret studies successfully. With each chapter including perspectives of both clinicians and scientists, Principles of Clinical Cancer Research provides balanced, instructive, and high-quality topic overviews and applications that are accessible and thorough for anyone in the field. Key Features: Gives real-world examples and rationales behind which research methods to use when and why Includes numerous tables featuring key statistical methods and programming commands used in everyday clinical research Contains illustrative practical examples and figures in each chapter to help the reader master the main concepts Provides tips and pointers for structuring a career, avoiding pitfalls, and achieving success in the field of clinical cancer research Access to fully downloadable ebook

This book will focus on DNA and histone methylation in epigenetics and describe how it is involved in the molecular mechanisms responsible for the development of cancer. Chapters will summarize the current knowledge of the molecular basis of DNA and histone methylation and explain how it is involved in cancer, describe the features of DNA and histone methylation associated with particular types of cancer, diagnostic/therapeutic applications, and future directions of DNA and histone methylation as cancer targets.

Survival analysis generally deals with analysis of data arising from clinical trials. Censoring, truncation, and missing data create analytical challenges and the statistical methods and inference require novel and different approaches for analysis. Statistical properties, essentially asymptotic ones, of the estimators and tests are aptly handled in the counting process framework which is drawn from the larger arm of stochastic calculus. With explosion of data generation during the past two decades, survival data has also enlarged assuming a gigantic size. Most statistical methods developed before the millennium were based on a linear approach even in the face of complex nature of survival data. Nonparametric nonlinear methods are best envisaged in the Machine Learning school. This book attempts to cover all these aspects in a concise way. Survival Analysis offers an integrated blend of statistical methods and machine learning useful in analysis of survival data. The purpose of the offering is to give an exposure to the machine learning trends for lifetime data analysis. Features: Classical survival analysis techniques for estimating statistical functional and hypotheses testing Regression methods covering the popular Cox relative risk regression model, Aalen's additive hazards model, etc. Information criteria to facilitate model selection including Akaike, Bayes, and Focused Penalized methods Survival trees and ensemble techniques of bagging, boosting, and random survival forests A brief exposure of neural networks for survival data R program illustration throughout the book

This book provides a concise yet comprehensive review of the morphological, biochemical, electrical, mechanical, and metabolic properties of vascular smooth muscle, the regulation of vascular activities and the intracellular signaling involved. It particularly focuses on newly identified vasoactive agents, enzymes and transduction mechanisms. It also discusses the latest findings in the regulation of cerebral, coronary and pulmonary circulation as well as vascular activity under hypoxia and ageing. The second edition intends to update the contents of the first edition with the latest achievements in the regulation of vascular activities from biochemical, structural, genetic, physiological, and pharmacological aspects. In addition, two new chapters related to microRNA and extracellular vesicles have been added to reflect their newly discovered important roles in vascular activities. The contraction and dilatation activities of vasculature are of fundamental importance for maintaining circulation homeostasis and adapting to physiological changes. Over the last four decades, there have been significant advances in our understanding of the biochemical, structural, genetic, physiological, and pharmacological aspects of vascular activity regulation, and these insights into the responsiveness of blood vessels under normal and pathophysiological conditions help to provide valuable weapons in the fight vascular diseases. The book is of interest to researchers and graduate students, both in basic research and in clinic settings, in the field of vascular biology.

The purpose and subject of this book is to provide a comprehensive overview of all types of phantoms used in medical imaging, therapy, nuclear medicine and health physics. For ionizing radiation, dosimetry with respect to issues of material composition, shape, and motion/position effects are all highlighted. For medical imaging, each type of technology will need specific materials and designs, and the physics and indications will be explored for each type. Health physics phantoms are concerned with some of the same issues such as material heterogeneity, but also unique issues such as organ-specific radiation dose from sources distributed in other organs. Readers will be able to use this book to select the appropriate phantom from a vendor at a clinic, to learn from as a student, to choose materials for custom phantom design, to design dynamic features, and as a reference for a variety of applications. Some of the information enclosed is found in other sources, divided especially along the three categories of imaging, therapy, and health physics. To our knowledge, even though professionally, many medical physicists need to bridge the three catagories described above.