Colorectal cancer has for more than two decades served as the paradigm for the multi-step concept of cancer initiation and progression. Perhaps more than any other organ site, cancer of the colon is extensively characterized at the molecular level. We are now entering a time when molecular classification, rather than histologic classification, of cancer subtypes is driving the development of clinical trials with emerging targeted therapies. The book will focus on the progression from the identification of mutations that drive colorectal cancer initiation and progression to the search for novel therapies to treat the disease.

This volume details protocols on rationale design of therapeutic siRNA molecules and its encapsulation with smart vehicles to overcome the barriers to an effective administration in vivo. 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, Design and Delivery of SiRNA Therapeutics aims to ensure successful results in the further study of this vital field.

This detailed book focuses on cutting-edge methods for Parkinson's disease (PD) research, such as the analysis of the prion-like properties of -synuclein, mitochondrial functions related to the PINK1-Parkin pathway/CHCHD2, the endolysosome pathway related to LRRK2, VPS35, and ATP13A2 using cultured cells (including patient iPS cells), deep brain stimulation therapy, classic mitochondrial toxins related to PD, and genetic associations and screenings using mammalian and invertebrate genetic models of PD. The collection intends to serve as an introductory protocol book for basic research on PD pathogenesis. Written for the highly successful Methods in Molecular Biology series, 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, Experimental Models of Parkinson's Disease is an ideal guide for researchers continuing to work toward making PD risk predictable and surmountable.

Embryonic stem cells and adult stem cells are the two major types of stem cells that have been used for experimental and clinical studies. Embryonic stem cells are totipotent cells that have the capability to differentiate into any type of cell in the body. In Cellular Cardiomyoplasty: Methods and Protocols, expert researchers in the field detail many of the methods which are now commonly used to study cellular cardiomyoplasty. Methods and techniques described in this volume use only adult stem cells or adult progenitor cells.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 key tips on troubleshooting and avoiding known pitfalls. Authoritative and Practical, Cellular Cardiomyoplasty: Methods and Protocols will benefit the cardiologist, cardiothoracic surgeons, biologist (cell, molecular, or structural), biochemist, and physiologist who are interested in understanding and treating damaged myocardium and failing heart.

Intended for students and general readers alike, this encyclopedia covers the history of human medical experimentation, for better and worse, from the time of Hippocrates to the present. Thanks to medical experiments performed on human subjects, we now have vaccines against smallpox, rabies, and polio. Yet the advances that saved lives too often involved the exploitation of vulnerable populations. Covering the history of human medical experimentation from the time of Hippocrates to today, this work will introduce readers to the topic through a mixture of essays and ready-reference materials. The book covers the experiments themselves; the people, companies, and government agencies that carried them out; the relevant medical and sociopolitical background; and the legislation and other protective measures that arose as a result. The encyclopedia is divided chronologically into six periods: pre-19th century, the 19th century, the pre-World War II 20th century, the World War II era, the Cold War era, and the post-Cold War period to today. Each period begins with an introductory essay and ends with a bibliography. Alphabetically arranged entries in each section cover pertinent people, experiments, and topics. The volume is enriched throughout with a wealth of primary sources, such as physicians' descriptions of their experiments. Medical experiments are not just a thing of the past, and readers will also learn about questions and debates related to contemporary efforts to advance medical science.

The role of free radicals and oxidative stress in neurological disorders has only recently been recognized, leaving clinical neurologists to seek in vain for information on the subject even in major textbooks. What published information there is may consist of brief reminders of the possible association of superoxidase dismutase with familial amyotrophic lateral sclerosis and nitrous oxide with migraine. With luck they may also find information on the purported role of free radicals in the pathogenesis of traumatic brain injury. Oxidative Stress and Free Radical Damage in Neurology sets the record straight, focusing on clinical and research issues regarding the interplay of free radicals and the human nervous system. Crucially, the chapters cover numerous antioxidants and their possible therapeutic role in neurological disorders. Key illnesses such as epilepsy, multiple sclerosis and Parkinson's are analyzed, and chapters also examine more general issues such as the link between free radicals and inflammation of the central nervous system. Clinicians and laboratory researchers alike will find that this book augments their understanding not only of the widespread involvement of free radicals in the central nervous system but also of some uncertainties surrounding whether free radical damage in neurology plays a primary or secondary role.

This volume provides an overview on the influence of Extracellular Matrix (ECM) on tumor progression. It covers topics such as signaling induced by structural ECM proteins including collagen and fibronectin, the control of ECM deposition and the turnover in tumors. Also discussed are the migration of cells through basement membranes and the function of proteoglycans including lumican and veriscan in tumor progression. Biomaterial-based in-vitro models as well as C. elegans models of the tumor microenvironment are used to show how these models can lead to a greater understanding of the disease mechanisms that promote cancer progression. The book addresses researchers working on cancer biology or ECM, and oncologists alike.

The book "STEM CELL THERAPY FOR ORGAN FAILURES" edited by Dr. S. Indumathi demonstrates the In Vitro and In vivo therapeutic strategies and applications of pre- and post-natal stem cells for treating the failures of various organ systems of our body in a wide perspective. It explores the past, present and the futuristic approach of the exciting field of stem cells and its intriguing properties involved in tissue repair and regeneration. The prime focus of this volume is to unravel the basic, advanced, therapeutic and translational approaches put-forth so far in the field of stem cells and regenerative medicine at research, pre-clinical and clinical levels. Stem cells has ushered in widespread interest and exciting possibilities for cell based therapies, albeit failures do prevail and small uncontrolled phase I/II studies are only signals generating, rather than definite proof of concept thereby limiting its applicability in curative therapeutics. Despite certain initiatives and meticulous untiring efforts, bringing this basic bench side research into advanced transitional bedside remained a challenge. Thus, this book embarked upon the expanding researches in these areas that seem decisive in improvising regenerative medical therapeutics, thereby leading to further path-breaking studies that cure all health challenges facing mankind. Overall, this book reveals the imperativeness of various stem cell sources and its utility in curative therapeutics.

This text is a review of molecular immunohematology (MI). It draws from analyses and case studies around the world and details many techniques used in many labs. It is aimed at anyone interested in how MI is changing blood bank and transfusion medicine.

This installment in the Techniques in Life Science and Biomedicine for the Non-Expert series aims to describe ESR spectroscopy as a tool for different applications, such as Healthcare & Pharmaceutical Science, Paleontology & Geochronology and Food Science. In keeping with the series theme, this text is presented in such a manner that the amateur researcher or graduate student can absorb it, while highlighting recent advances and applications of the field. Chapters include solved examples and questions to reinforce themes and encourage readers to apply what they've learnt.

Chronic diseases are the leading cause of deaths worldwide and according to the World Economics Council and the Harvard School of Public Health, the cost of chronic diseases is expected to reach a staggering 48% of global gross domestic product by the year 2030. The urgency of the issue was demonstrated in 2011 when for only the second time in its existence, the U.N. General Assembly brought a health issue to the floor for consideration: chronic diseases.

To date, most considerations of the issue have approached the topic from the vantage point that chronic diseases are a myriad of largely unconnected diseases and conditions arising in diverse tissues, organs and physiological systems. This book, "Immunotoxicity, Immune Dysfuction, and Chronic Disease," deviates from that prior model. It considers the interconnectivity of chronic diseases with both environmental insult of the immune system and subsequent immune dysfunction and inflammatory dysregulation as the underlying basis for many, if not most, chronic diseases.

This change in the perception of environment-immune linkages to chronic disease is significant and has immediate implications both for the prevention of disease as well as for the development of more effective therapeutic approaches. Rather than considering environmental factors and types of reported immune alterations ("e.g., " depressed humoral immunity) as is common in books involving immunotoxicity, the present book approaches the environment-immune-disease triad from the standpoint of the disease. Each chapter emphasizes one or more specific immune dysfunction-based chronic disease(s) or condition(s) ("e.g., " asthma, atherosclerosis, multiple sclerosis, lupus) and describes: 1) the suggested environmental risk factors, 2) the underlying immune dysfunction(s) associated with the disease and 3) the overall health consequences of the disease.

This book is an early entry for a new Toxicology book series for Springer titled: Molecular and Integrative Toxicology (MaIT). The series will feature detailed research information, but in the context of a more integrative or holistic framework. As part of this framework, the chapters will contain a section on Key Points as well as Recommendations where appropriate. The goal is to cover the most timely, state-of-the-art issues in toxicology as well as to ensure that the information is maximally accessible for research scientists, teachers, physicians and students. We are particularly grateful to the numerous chapter authors for providing comprehensive and expert disease-oriented contributions. We are also appreciative of their willingness to consider their material not as disparate pieces of what has become a major health crisis, but rather as key pieces in a network of apparently interconnected health challenges."

This volume details a collection of laboratory protocols to study asthma in mice and humans. Chapters cover animal models of asthma, methods to measure asthma-related molecules, protocols to detect, isolate, culture and stimulate cells that contribute to asthma in mice and humans, methods to deplete these cells in vivo and study responses of intact airway tissues ex vivo. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Asthma: Methods and Protocols aims to be a foundation for future studies and to be a source of inspiration for new investigations in the field.

Navigating research careers is often highly challenging for early career researchers (ECRs) in the social sciences. The ability to thrive in research careers is complex and requires "soft" people and management skills and resilience that often cannot be formally taught through university coursework. Written from a peer perspective, this book provides guidance and establishes emotional rapport on topical issues relevant for ECRs in academia and industry. The authors are ECRs who have been successful in navigating their careers, and they seek to connect with readers in a supportive and collegial manner. Each chapter includes elements of story-telling and scientific thinking and is organized into three parts: (1) a personal story that is relevant to the topic; (2) key content on professional and personal effectiveness based on evidence in the psychological, sociological, and/or management sciences; and (3) action points and practical recommendations. The topics covered are specifically curated for people considering undertaking research careers or already working in research, including: Work Hard, Snore Hard: Recovery from Work for Early Career Researchers Networking and Collaborating in Academia: Increasing Your Scientific Impact and Having Fun in the Process Accelerating Your Research Career with Open Science Engaging with the Press and Media Make Your Science Go Viral: How to Maximize the Impact of Your Research Exploring the Horizon: Navigating Research Careers Outside of Academia Thinking like an Implementation Scientist and Applying Your Research in Practice Survival Guide for Early Career Researchers summarizes relevant evidence-based research to offer advice in strategic but also supportive ways to ECRs. It is an essential go-to practical resource for PhD students, postdoctoral fellows, and junior faculty. This book will also benefit senior researchers who are serving as mentors or delivering professional development programs, administrators and educators in institutions of higher learning, and anyone with an interest in building a successful research career.

This volume details the history of Retinitis Pigmentosa and current treatment options. Chapters guide readers through CRISPR, gene therapy, stem cell therapy, next-generation sequencing methods, gene editing, and translational applications of other therapies to the treatment of Retinitis Pigmentosa. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Retinitis Pigmentosa aims to be a useful practical guide to researches to help further their study in this field.

This book describes in 13 chapters mechanisms of P450 used to monooxygenate substrates via the NAD(P)H/O2 pathway using its peroxidase and peroxygenase functions. P450 also utilizes peroxides, peracids, periodate and iodosobenzene to oxygenate substrates via the shunt pathway. Also described are mechanisms used in the oxidation of pharmaceuticals by CYP3A4; acyl- carbon cleavage by CYP17A1, CYP19A1 and CYP51A1; metabolism of tetrabromodiphenyl ethers and bile acids by CYP2B6 and CYP3A4; metabolism of -6 and -3 polyunsaturated fatty acids; H2O2-mediated peroxygenation of substrates using substrate misrecognition; P450 oxidative reactions using electrochemical methods; electron transfer to P450 by redox proteins; hydroxylation of 1,8-cineole by P450cin; and peroxygenation by unspecific peroxygenases using H2O2. The topics covered are relevant to P450 researchers, professors and students from a variety of disciplines ranging from pharmacology, toxicology and microbiology to chemistry.

This volume details experimental protocols to study structure and function of hepatocytes in vivo and in vitro, and for characterizing heterogeneity and plasticity of hepatocytes in healthy and in injured liver. Chapters guide readers through separating hepatocyte subfractions, characterizing the heterogeneity, novel culture systems, hepatocyte-like cells from human pluripotent stem cells, analyzing drug metabolism, monitoring protein sorting, manipulating gene expression, and methods for expanding primary hepatoblastoma and identifying hepatocellular carcinoma subtypes. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and cutting-edge, Hepatocytes: Methods and Protocols aims to provide techniques to further understand molecular mechanisms involved in the regulating hepatocyte functions and underlying liver diseases.

This book provides a comprehensive overview of the latest advances in a wide range of biomaterials for the development of smart and advanced functional materials. It discusses the fundamentals of bio-interfacial interactions and the surface engineering of emerging biomaterials like metals and alloys, polymers, ceramics, and composites/nanocomposites. In turn, the book addresses the latest techniques and approaches to engineering material surfaces/interfaces in, e.g., implants, tissue engineering, drug delivery, antifouling, and dentistry. Lastly, it summarizes various challenges in the design and development of novel biomaterials. Given its scope, it offers a valuable source of information for students, academics, physicians and particularly researchers from diverse disciplines such as material science and engineering, polymer engineering, biotechnology, bioengineering, chemistry, chemical engineering, nanotechnology, and biomedical engineering for various commercial and scientific applications.

Two decades have passed since trinucleotide repeat expansion was first discovered in genes responsible for certain neurological diseases. Since then, new technologies have developed and innovative concepts have emerged, which may prove useful in devising therapeutic approaches to neurological diseases. Divided into six convenient sections, Trinucleotide Repeat Protocols, Second Edition covers a wide range of topics such as an overview of trinucleotide repeat diseases, synaptic plasticity, embryonic stem (ES) cell-related protocols with a focus on HD, RNA-related protocols, and analysis of epigenetic modification in fragile X syndrome. This edition focuses not only on direct analysis of trinucleotide repeat diseases but also on alternative approaches for the analysis of trinucleotide repeat diseases, with the hope that this will result in a better understanding of the mechanisms and future therapeutic prospects for treatment of these diseases. Written in the 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 protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Trinucleotide Repeat Protocols, Second Edition seeks to serve researchers with its thorough methodologies on this expanding field.

This book examines the sequence of events and methodology in the industrial clinical research process; a reference for multidisciplinary personnel. It is the conceptual framework involving the philosophical, economic, political, historical, regulatory, planning, and marketing aspects of the process.

Combining the latest thinking in the field with practical, step-by-step guidance, the Third Edition of John W. Creswell and Vicki L. Plano Clark's Designing and Conducting Mixed Methods Research now covers seven mixed methods designs with accompanying journal articles illustrating each design. The authors walk readers through the entire research process, and present updated examples from published mixed methods studies drawn from multiple disciplines. In addition, this new edition includes information about the dynamic and evolving nature of the field of mixed methods research, four additional methodological approaches, and coverage of new directions in mixed methods.

Data Monitoring in Clinical Trial: A Practical Perspective ist die erweiterte 2. Auflage des weit verbreiteten und viel beachteten Fachbuchs, das erstmals im Jahr 2002 erschienen ist. Es bietet einen fundierten und aktuellen UEberblick uber Datenkontrollkomitees, deren Einrichtung, Zweck und Zustandigkeiten. - Enthalt direkt umsetzbare Handreichungen fur alle, die klinische Studien verwalten und durchfuhren, sowie fur Mitglieder von Datenkontrollkomitees. - Liefert Mitgliedern von Behoerden- und Ethikkommissionen Einblicke in die Kontrolle klinischer Daten. - Diskutiert Themen mit Relevanz fur diejenigen, die in den USA und in Europa an klinischen Studien arbeiten. Die praktischen Handlungsansatze in diesem Buch sind fur Experten aus dem akademischen Bereich, bei Regierungsstellen und aus der Industrie, vor allem fur Medizinstatistiker, Kliniker, Koordinatoren von klinischen Studien von Nutzen, ob sie Studien durchfuhren und/oder begleiten. Ebenso relevant ist dieses Praktikerbuch fur Mitarbeiter bei Regulierungsstellen und im Bereich der Bioethik.

Tamoxifen Tales: Suggestions for Scientific Survival presents a case study describing the academic journey of teams behind major advances in medical sciences, highlighting lessons learned that are applicable to the next generation of scientists. This book provides a manual on the successful mentoring of young scientists, including stories describing how training experience shaped careers to become leaders in academia and the pharmaceutical industry. The book documents Professor V. Craig Jordan's 50-year career in medical sciences that led to the discovery and development of Selective Estrogen Receptor Modulators (SERMs), which became the standard of women's healthcare around the world. Additionally, it illustrates the versatility of a scientist with a commitment to serving societies. This important resource will be a useful and interesting book for established medical scientists, research mentors and advanced students wanting to chart a successful and impactful research career.

Upon completion of the human genome project over 800 G protein-coupled receptor 1 (GPCR) genes, subdivided into five categories, were identified. These receptors sense a diverse array of stimuli, including peptides, ions, lipid analogues, light and odour, in a discriminating fashion. Subsequently, they transduce a signal from the ligand-receptor complex into numerous cellular responses. The importance of GPCRs is further reflected in the fact that they constitute the most common target for therapeutic drugs across a 2 wide range of human disorders. Phylogenetic analysis of GPCRs produced the GRAFS classification system, which subdivides GPCRs into five discrete families: glutamate, rhodopsin, adhesion, frizzled/taste2 and secretin receptors. The adhesion-GPCR family 2 can be further subdivided into eight groups. The field of adhesion-GPCR biology has indeed become large enough to require a volume dedicated solely to this field. The contributors to this book have made a courageous effort to address the key concepts of adhesion-GPCR biology, including the evolution and biochemistry of adhesion-GPCRs; there are extensive discussions on the functional nature of these receptors during development, the immune response and tumourgenesis. Finally, there are chapters dedicated to adhesion-GPCR signalling, an area of intense investigation.

This volume provides methodologies for ES and iPS cell technology on the study of cardiovascular diseases. Chapters guide readers through protocols on cardiomyocyte generation from pluripotent stem cells, physiological measurements, bioinformatic analysis, gene editing technology, and cell transplantation studies. 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, Pluripotent Stem-Cell Derived Cardiomyocytes aims to help researchers set up experiments using pluripotent stem cell-derived cardiac cells.

The current textbook has been written as a help to medical / health professionals and students for the study of modern Bayesian statistics, where posterior and prior odds have been replaced with posterior and prior likelihood distributions. Why may likelihood distributions better than normal distributions estimate uncertainties of statistical test results? Nobody knows for sure, and the use of likelihood distributions instead of normal distributions for the purpose has only just begun, but already everybody is trying and using them. SPSS statistical software version 25 (2017) has started to provide a combined module entitled Bayesian Statistics including almost all of the modern Bayesian tests (Bayesian t-tests, analysis of variance (anova), linear regression, crosstabs etc.). Modern Bayesian statistics is based on biological likelihoods, and may better fit clinical data than traditional tests based normal distributions do. This is the first edition to systematically imply modern Bayesian statistics in traditional clinical data analysis. This edition also demonstrates that Markov Chain Monte Carlo procedures laid out as Bayesian tests provide more robust correlation coefficients than traditional tests do. It also shows that traditional path statistics are both textually and conceptionally like Bayes theorems, and that structural equations models computed from them are the basis of multistep regressions, as used with causal Bayesian networks.