Engineered antibodies currently represent over 30% of biopharmaceuticals in clinical trials and their total worldwide sales continue to increase significantly. The importance of antibody applications is reflected in their increasing clinical and industrial applications as well as in the progression of established and emerging production strategies. This volume provides detailed coverage of the generation, optimization, characterization, production and applications of antibody. It provides the necessary theoretical background and description of methods for the expression of antibody in microbial and animal cell cultures and in transgenic animals and plants. There is a strong focus on those issues related to the production of intrabodies, bispecific antibody and antibody fragments and also to novel applications in cancer immunotherapy.

Pancreatic cancer is the fourth leading cause of cancer death in the United States. Every year, about 33,700 people in the United States will be diagnosed with pancreatic cancer and over 32,000 patients will die from the disease. The median survival of patients with advanced pancreatic cancer is about 6-months. This dismal picture of pancreatic cancer is mainly due to the lack of early diagnosis and effective treatment for patients with advanced disease. To increase the survival rate of pancreatic cancer patients, better tumor markers for diagnosis and new molecular targets for drug development are desperately needed. A lot of effort has been made in searching for pancreatic cancer-causing genes or genes associated with progression of malignant behavior in pancreatic cancer. As a result, alterations in the expression of several cancer-related genes have been identified in pancreatic tumors. The identification and characterization of these cancer-related genes have significantly increased our understanding of pancreatic cancer development, but unfortunately the treatment of pancreatic cancer has not advanced as much in the past 20 years.

Over the past decade, tremendous advances have been made in the field of cancer drug discovery, particularly, in the area of molecular and genetic models and technologies. Many of those advanced models and technologies have been applied to the drug discovery processes for pancreatic cancer. In this book, a team of experts will describe the latest development in the application of these models and technologies in pancreatic cancer. The authors include basic researchers as well as clinicians who work in the front-line of the war against pancreatic cancer and have the first-hand experience on these cutting-edge tools and techniques. The book can be divided into two general areas: 1) model systems and 2) genomics and proteomics tools. In recent years there have been a lot of advances in the model systems for pancreatic cancer, including the further characterization of normal and cancerous pancreatic cell lines, the establishment of transgenic mouse models that recapitulate the initiation and progression of human pancreatic cancer, the development of a new xenograft model system for the evaluation of novel agents, and the establishment of a zebrafish pancreatic cancer model. The first four chapters of the book will be devoted to these models. The advances in genomics and proteomics research have made a major impact in cancer drug discovery. A number of these omics-based tools and techniques have been applied in the pancreatic cancer drug discovery. Chapters 5-9 of the book will discuss techniques for genome-wide examination of gene expression, copy number, methylation, function and regulation. Chapters 10-11 will discuss in situ techniques for studying chromosomal and gene copy number abnormalities as well protein expression changes in cancer samples. Chapters 12-14 will focus on techniques for global examination of protein expression levels in biospecimens obtained from pancreatic cancer patients. Cancer drug discovery has become more and more target-centric. "

The title "Nano Biotechnology for Biomedical and Diagnostics Research" will address research aspects related to nanomaterial in imaging and biological research, nanomaterials as a biosensing tool, DNA nanotechnology, nanomaterials for drug delivery, medicinal and therapeutic application and cytotoxicity of nanomaterials. These topics will be covered by 16 different manuscripts. Amongst the authors that will contribute to the book are major scientific leaders such as S. Weiss - UCLA, I. Willner, and G. Golomb -- HUJI, S. Esener - UCSD, E.C. Simmel - Tech. Univ. Munchen, I. Medintz -- NRL, N. Hildebrandt - Universit Paris and more. The manuscripts in the book intend to present specifically biological, diagnostics and medical problems with their potential solution by nano technology or materials. In this respect this book is unique, since it would arise from the biological problems to the nano technology possible solution and not vice versa.

This volume comprehensively covers the multiplicity and diversity of mechanisms underlying patient resistance to currently approved anti-cancer drugs, including tyrosine kinase inhibitors and monoclonal antibodies, blockers of growth factor receptors and their downstream pathways, which play essential functions in cancer progression. Each chapter will cover a specific group of targets and the cognate drugs, along with molecular modes of innate and evolving resistance.

This volume gives a general summary of the current understanding of lymphatic metastasis and the possibilities of more specific detection of lymph node metastasis. It describes in detail the procedure of sentinel lymph node detection in urogenital tumors, neck and thyroid tumors, malignant melanoma, gastric and colorectal cancer and tumors of the breast. The potential and limitations of this new method are discussed. This book provides comprehensive insight into a both clinically and scientifically important new field which is bringing about a marked improvement in the treatment of malignant tumors.

This volume will consider one of ICH's major categories, Safety i.e. topics relating to in vitro and in vivo pre-clinical studies (Carcinogenicity Testing, Genotoxicity Testing, etc.). Since the start of the ICH process, many guidelines have been written, but even after ICH6 no explanations have been given during a formal Congress about the background of the ICH Guidance documents. Even more important than what has been written, might have been those thoughts of the experts that are not included in the Guidance documents. Why has the guideline been written as it is written, and why have some aspects been deleted. These and other related questions are the contents of this book, written by experts who were involved in the ICH process. Furthermore, the chapters will contain discussions on the "lessons learnt" and "future developments".

Required reading in many medical and healthcare institutions, How to Read a Paper is a clear and wide-ranging introduction to evidence-based medicine and healthcare, helping readers to understand its central principles, critically evaluate published data, and implement the results in practical settings. Author Trisha Greenhalgh guides readers through each fundamental step of inquiry, from searching the literature to assessing methodological quality and appraising statistics. How to Read a Paper addresses the common criticisms of evidence-based healthcare, dispelling many of its myths and misconceptions, while providing a pragmatic framework for testing the validity of healthcare literature. Now in its sixth edition, this informative text includes new and expanded discussions of study bias, political interference in published reports, medical statistics, big data and more. Offers user-friendly guidance on evidence-based healthcare that is applicable to both experienced and novice readers Authored by an internationally recognised practitioner and researcher in evidence-based healthcare and primary care Includes updated references, additional figures, improved checklists and more How to Read a Paper is an ideal resource for healthcare students, practitioners and anyone seeking an accessible introduction to evidence-based healthcare.

Antibiotics are truly miracle drugs. As a class, they are one of the only ones that actually cure disease as opposed to most drugs that only help relieve symptoms or control disease. Since bacteria that cause serious disease in humans are becoming more and more resistant to the antibiotics we have today, and because they will ultimately become resistant to any antibiotic that we use for treatment or for anything else, we need a steady supply of new antibiotics active against any resistant bacteria that arise. However, the antibiotics marketplace is no longer attractive for large pharmaceutical companies, the costs of development are skyrocketing because of ever more stringent requirements by the regulatory agencies, and finding new antibiotics active against resistant strains is getting harder and harder. These forces are all combining to deny us these miracle drugs when we need them the most. I provide a number of possible paths to shelter from this perfect storm.

The Endoplasmic Reticulum (ER) is an organelle with extraordinary signaling and homeostatic functions. It is the organelle responsible for protein folding, maturation, quality control and trafficking of proteins destined for the plasma membrane or for secretion into the extracellular environment. Failure, overloading or malfunctioning of any of the signaling or quality control mechanisms occurring in the ER may provoke a stress condition known as ER stress . Accumulating evidence indicates that ER stress may dramatically perturb interactions between the cell and its environment, and contribute to the development of human diseases, ranging from metabolic diseases and cancer to neurodegenerative diseases, or impact therapeutic outcome. This book primarily focuses on the pathophysiology of ER stress. It introduces the molecular bases of ER stress, the emerging relevance of the ER-mitochondria cross-talk, the signaling pathways engaged and cellular responses to ER stress, including the adaptive Unfolded Protein Response (UPR), autophagy as well as cell death. Next the book addresses the role of ER stress in physiology and in the etiology of relevant pathological conditions, like carcinogenesis and inflammation, neurodegeneration and metabolic disease. The last chapter describes how ER stress pathways can be targeted for therapeutic benefit. Altogether, this book will provide the reader with an exhaustive view of ER stress biology and the latest insights in the role of ER stress in relevant human diseases."

Exercise Genomics encompasses the translation of exercise genomics into preventive medicine by presenting a broad overview of the rapidly expanding research examining the role of genetics and genomics within the areas of exercise performance and health-related physical activity. Leading researchers from a number of the key exercise genomics research groups around the world have been brought together to provide updates and analysis on the key discoveries of the past decade, as well as lend insights and opinion about the future of exercise genomics, especially within the contexts of translational and personalized medicine. Clinicians, researchers and health/fitness professionals will gain up-to-date background on the key findings and critical unanswered questions across several areas of exercise genomics, including performance, body composition, metabolism, and cardiovascular disease risk factors. Importantly, basic information on genomics, research methods, and statistics are presented within the context of exercise science to provide students and professionals with the foundation from which to fully engage with the more detailed chapters covering specific traits.

Exercise Genomics will be of great value to health/fitness professionals and graduate students in kinesiology, public health and sports medicine desiring to learn more about the translation of exercise genomics into preventive medicine.

Over the last decade the development of new molecular biology tools, advanced microscopy, live imaging and systems biology approaches have revolutionized our conception of how embryonic development proceeds. One fundamental aspect of development biology is the concept of morphogenesis: understanding how a group of multipotent cells organize and differentiate into a complex organ. In Kidney Development: Methods and Protocols, expert researchers in the field detail different approaches to tackle kidney development. These approaches include culture and live imaging aspects of kidney development, analyzing the 3-dimensional aspects of branching morphogenesis as well as nephrogenesis, manipulation of the gene/protein expression during kidney development as well as in the adult kidney, and how to assess kidney malformation and disease. 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, Kidney Development: Methods and Protocols seeks to aid scientists in the further study of the process of morphogenesis which is fundamental important not only for studying developmental biology but also for regenerative medicine.

The year 2010 marks the centennial for the identification of histamine and the first glimpse of its many physiological functions. From these initial findings a rich tapestry of research has uncovered roles for histamine in almost every physiological process with new findings emerging every year. These diverse roles of histamine have made for fertile ground for the discovery of novel therapeutics, and these drugs have been so successful that the term "antihistamine" has entered the common lexicon. This volume is an attempt to give a snapshot in time as to the current understanding of the role of histamine in just one important therapeutic area-inflammation. The first three chapters provide some background context for the rest of the book starting out with a historical perspective by Figueroa and Shankley. Bongers et al provide an overview of the pharmacology of the four histamine receptors and the chapter by Hiroshi Ohtsu describes how histamine is synthesized as well as the insights derived from mice where this synthesis is disrupted. The next several chapters discuss disease areas where histamine is known to be involved. Chapter 4 by Thomas Taylor-Clark outlines the role of histamine in allergic rhinitis, an area were antihistamines are commonly used. This is also true for ocular allergy as discussed by Ohbayashi et al. Both of these chapters highlight aspects of these conditions that are still not well-controlled and suggest the utility of new antihistamines targeting other histamine receptors.

This book provides in-depth information on the applications of cannabis products as a legitimate medicine in treating a variety of diseases and disorders in domestic animals. Pharmacology and toxicology of cannabinoids and their effects on the endocannabinoid system, which is involved in the regulation of diverse physiological and cognitive processes, are discussed in detail. Furthermore, the book reviews development and testing of cannabis based medical products and introduces the nutritional components of cannabis plants. Cannabis as a therapeutic in veterinary medicine is gaining interest among owners and practitioners. Numerous studies have been completed or are currently underway that analyze the potential of clinical application of cannabinoid and terpenoid molecules. In this book the authors take a comprehensive look at previous studies in animal and human models and discuss translational applications based on these scientific data. This seminal text serves as a go-to resource for veterinary practitioners on cannabinoid therapy. It will also serve as a foundation for clinicians and researchers interested in this emerging field of veterinary medicine.

This book offers a comprehensive but highly readable compilation of papers on the role of dopamine in sleep and sleep disorders. Leading experts in sleep medicine, psychiatry and neuroendocrinology provide a broad perspective on the field, from established theories to the latest research advances. Accordingly, it represents an interdisciplinary, cutting-edge guide for sleep disorder specialists, sleep researchers, psychiatrists, neurologists, pulmonologists, psychologists, and behavioral sleep medicine specialists.

This unique book is the proceedings of The Future of Life and the Future of our Civilization symposium, which was held in May of 2005 in Germany. It is unique since it contains articles of the Future in all aspects of our life. Besides, until now such publications are absent. In this book we can find articles about the spread of life trough out the cosmos and about solar evolution, about origin of life and about cardiology in XXIst century, about structural regularities of encoding in DNA chromosomes, about preservation of biodiversity in marine systems and about defeat of aging, about life-time of technological civilization and about the future of the poor, marginalized populations, about the early cancer diagnositcs of skin, about human clonius and about transition to the next level civilization."

Dr. Gordon Meiklejohn was a world renowned physician, and Chairman of the Department of Medicine at the University of Colorado. He is best known for being a catalyst in researching, diagnosing, and inoculating for the flu virus, and was instrumental in the eradication of Smallpox.Dr. Meiklejohn was the son of Alexander Meiklejohn. He excelled in academics and sports, especially ice hockey, and was twice invited to participate on the U.S. Olympic Hockey teams.

This book, written by one of the leaders in the field of the neurosciences, will give an explanation of the symptoms and eventual untimely suicide of one of literatures greatest authors; Virginia Woolf. The sources used are letters and statements from Woolf herself, the literature she wrote and comments, letters and any other documentation that referred to her mental state and her medical status. The author will use current insight into depression, the mental consequences of child abuse and drug interactions/effects to illustrate this case study. The book should appeal to researchers in the neurosciences, psychology and psychiatry as well as to a broader audience, mainly individuals who are interested in the (external and internal) forces that drove Woolf to write her material.

This book, an international collaborative effort in the area of molecular respiratory research, showcases a broad range of multidisciplinary approaches to unravel and analyze the underlying mechanisms of a spectrum of respiratory ailments. It discusses immunological and genetic respiratory disorders, cancer, respiratory allergies and cough, sleep disordered breathing and many others. Exciting new results and up-to-date critical overviews of widely debated topics pertaining to respiratory disorders are presented. The contributions provide evidence for the growing interest of the international community of researchers in the field of respiration. The book incorporates modern molecular approaches to diagnostic and treatment solutions, underscoring the need for rational, evidence-based treatment methods. Combining cutting edge basic and clinical research with expert knowledge and experience this book is essential reading for medical students, research scientists and practicing specialists in pulmonology, immunology and allergology.

This book is unique in covering a wide range of design and analysis issues in genetic studies of rare variants, taking advantage of collaboration of the editors with many experts in the field through large-scale international consortia including the UK10K Project, GO-T2D and T2D-GENES. Chapters provide details of state-of-the-art methodology for rare variant detection and calling, imputation and analysis in samples of unrelated individuals and families. The book also covers analytical issues associated with the study of rare variants, such as the impact of fine-scale population structure, and with combining information on rare variants across studies in a meta-analysis framework. Genetic association studies have in the last few years substantially enhanced our understanding of factors underlying traits of high medical importance, such as body mass index, lipid levels, blood pressure and many others. There is growing empirical evidence that low-frequency and rare variants play an important role in complex human phenotypes. This book covers multiple aspects of study design, analysis and interpretation for complex trait studies focusing on rare sequence variation. In many areas of genomic research, including complex trait association studies, technology is in danger of outstripping our capacity to analyse and interpret the vast amounts of data generated. The field of statistical genetics in the whole-genome sequencing era is still in its infancy, but powerful methods to analyse the aggregation of low-frequency and rare variants are now starting to emerge. The chapter Functional Annotation of Rare Genetic Variants is available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

This book describes important developments and emerging trends in experimental and clinical cancer gene therapy. It reflects the tremendous advances made over recent years with respect to immunogenes, suicide genes and gene correction therapies, as well as in gene suppression and miRNA therapies. Many of the described strategies focus on the generation of more efficient and specific means of attack at known and novel cellular targets associated with tumor development and progression. The book also details parallel improvements in vector design, vector delivery, and therapeutic efficacy. It offers readers a stimulating, broad overview of advances in the field, linking experimental strategies to their clinical applications.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

In recent years, there have been major advances in the concepts and methodologies used in the study of retinal development at both cellular and molecular levels. These advanced methodologies have allowed and will continue to allow researchers to gain new insights into the molecular mechanisms underlying retinal development. In Retinal Development: Methods and Protocols, expert researchers in the field detail many of the protocols used for a wide range of experiments. These include protocols and techniques for manipulating gene expression in vivo, tracing cell fates with modernized classic blastomere manipulation in Xenopus and with Cre-based technique in mouse and in zebrafish, retinal regeneration and stem cell-based replacement, and ERG (function) recording and non-invasive imaging. 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, Retinal Development: Methods and Protocols provides methodologies crucial to the success of increasingly more complex and often challenging investigations in the fields of retinal development and other biological and biomedical research.

This unique reference work offers a diverse and interesting view of the remarkable history of treating disease and understanding human health. More than 500 entries, written in an A-Z format, cover the amazing changes that have taken place in the world of health and medicine. While other volumes may overwhelm readers with extraneous information, "Milestones in Health and Medicine" offers relevant and succinct entries. Each entry includes a definition of the topic, its history, and its current place in medicine today. This book also includes a preface, illustrations, helpful cross-references, sources for additional reading, and a list of entries by subject.

Diverse molecular, cellular, and environmental events must all come together to allow the successful formation of secondary cancers, metastases. The second edition of Metastasis Research Protocols, brings together updated versions of the seminal technique that were presented in the first edition and also includes new techniques that have recently been shown to be important in illuminating the processes underlying this important area of biology. Volume 2 presents techniques applicable at the level of living cells and tissues, and presents methodologies applicable to cell behaviour in vitro, in animal models and in mathematical constructs. The aim is the study of the interaction between cancer cells and their host/environment. The focus throughout is on the tools that have been shown to be helpful in unravelling the processes important in cancer metastasis. 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, Metastasis Research Protocols, Second Edition seeks to aid scientists in the further study of new methods in the area of metastasis research.

Computational methodologies and modeling play a growing role for investigating mechanisms, and for the diagnosis and therapy of human diseases. This progress gave rise to computational medicine, an interdisciplinary field at the interface of computer science and medicine. The main focus of computational medicine lies in the development of data analysis methods and mathematical modeling as well as computational simulation techniques specifically addressing medical problems. In this book, we present a number of computational medicine topics at several scales: from molecules to cells, organs, and organisms. At the molecular level, tools for the analysis of genome variations as well as cloud computing resources for medical genetics are reviewed. Then, an analysis of gene expression data and the application to the characterization of microbial communities are highlighted. At the protein level, two types of analyses for mass spectrometry data are reviewed: labeled quantitative proteomics and lipidomics, followed by protein sequence analysis and a 3D structure and drug design chapter. Finally, three chapters on clinical applications focus on the integration of biomolecular and clinical data for cancer research, biomarker discovery, and network-based methods for computational diagnostics.