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.

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.

The reader will soon find that this is more than a "how-to-do-it" book. It describes a philosophical approach to the use of statistics in the analysis of clinical trials. I have come gradually to the position described here, but I have not come that way alone. This approach is heavily influenced by my reading the papers of R.A. Fisher, F.S. Anscombe, F. Mosteller, and J. Neyman. But the most important influences have been those of my medical colleagues, who had important real-life medical questions that needed to be answered. Statistical methods depend on abstract mathematical theorems and often complicated algorithms on the computer. But these are only a means to an end, because in the end the statistical techniques we apply to clinical studies have to provide useful answers. When I was studying martingales and symbolic logic in graduate school, my wife, Fran, had to be left out of the intellectual excitement. But, as she looked on, she kept asking me how is this knowledge useful. That question, what can you do with this? haunted my studies. When I began working in bio statistics, she continued asking me where it was all going, and I had to explain what I was doing in terms of the practical problems that were being ad dressed."

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.

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.

The discovery of microRNAs and its role as gene expression regulators in human carcinogenesis represents one of the most important scientific achievements of the last decade. More recently, other non-coding RNAs have been discovered and its implications in cancer are emerging as well, suggesting a broader than anticipated involvement of the non-coding genome in cancer. Moreover, completely new and unexpected functions for microRNAs are being revealed, leading to the identification of new anticancer molecular targets. This book represents a comprehensive guide on non-coding RNAs and cancer, spanning from its role as cancer biomarkers, to providing the most useful bioinformatic tools, to presenting some of the most relevant discoveries, which indicates how these fascinating molecules act as fine orchestrators of cancer biology.

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.

Leland H. Hartwell Director, Fred Hutchinson Cancer Research Center, Nobel Laureate for Medicine, 2001 Yeast has proved to be the most useful single-celled organism for studying the fundamental aspects of cell biology. Resources are now available for yeast that greatly simplify and empower new investigations, like the presence of strains with each gene deleted, each protein tagged and databases on protein-protein interactions, gene regulation, and subcellular protein location. A powerful combination of genetics, cell biology, and biochemistry employed by thousands of yeast researchers has unraveled the complexities of numerous cellular processes from mitosis to secretion and even uncovered new insights into prion diseases and the role of prions in normal biology. These insights have proven, time and again, to foretell the roles of proteins and pathways in human cells. The collection of articles in this volume explores the use of yeast in pathway analysis and drug discovery. Yeast has, of course, supplied mankind's most ubiquitous drug for thousands of years. In one aspect, the role of yeast in drug discovery is much like the role of yeast in other areas of biology. Yeast offers the power of genetics and a repetoire of resources available in no other organism. Using yeast in the study of drug targets and metabolism can help to make a science of what has been largely an empirical activity. A science of drug discovery would permit rigorous answers to important questions.

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.

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.

This thesis presents a method for reliably and robustly producing samples of amyloid- (A ) by capturing them at various stages of aggregation, as well as the results of subsequent imaging with various atomic force microscopy (AFM) methods, all of which add value to the data gathered by collecting information on the peptide's nanomechanical, elastic, thermal or spectroscopical properties. Amyloid- (A ) undergoes a hierarchy of aggregation following a structural transition, making it an ideal subject of study using scanning probe microscopy (SPM), dynamic light scattering (DLS) and other physical techniques. By imaging samples of A with Ultrasonic Force Microscopy, a detailed substructure to the morphology is revealed, which correlates well with the most advanced cryo-EM work. Early stage work in the area of thermal and spectroscopical AFM is also presented, and indicates the promise these techniques may hold for imaging sensitive and complex biological materials. This thesis demonstrates that physical techniques can be highly complementary when studying the aggregation of amyloid peptides, and allow the detection of subtle differences in their aggregation processes.

That precursors of adult coronary artery disease, hypertension, and type II diabetes begin in childhood have been clearly established by the Bogalusa Heart Study. This unique research program has been able to follow a biracial (black/white) population over 35 years from childhood through mid-adulthood to provide perspectives on the natural history of adult heart diseases. Not only do these observations describe trajectories of cardio-metabolic risk variables leading to these diseases but provide a rationale for the need to begin prevention beginning in childhood. The trajectories of the burden of cardio-metabolic risk variables in the context of their fetal origin and chromosome telomere dynamics provide some insight into the metabolic imprinting in utero and aging process. The observed racial contrasts on cardio-metabolic risk variables implicate various biologic pathways interacting with environment contributing to the high morbidity and mortality from related diseases in our population. To address the seriousness of the onset of cardiovascular disease in youth, approaches to primordial prevention are described focussing on childhood health education as an important aspect of Preventive Cardiology.

This is an annual research series devoted to the examination of occupational stress, health and well being, with particular emphasis on the multi-disciplinary nature of occupational stress. The intent is to pull together the various streams of research from a variety of disciplines to better capture the significant bodies of work in occupational stress and well being. It provides a multidisciplinary and international perspective that gives a thorough and critical assessment of issues in occupational stress and well being. The theme for this volume, "Historical and Current Perspectives on Stress and Health" focuses on two main concerns: historical as well as current perspectives to occupational stress research and an emphasis on the healthy individual and organization.

The approach taken in this book is, to studies monitored over time, what the Central Limit Theorem is to studies with only one analysis. Just as the Central Limit Theorem shows that test statistics involving very different types of clinical trial outcomes are asymptotically normal, this book shows that the joint distribution of the test statistics at different analysis times is asymptotically multivariate normal with the correlation structure of Brownian motion ("the B-value") - irrespective of the test statistic. Thus, this book offers statisticians an accessible, incremental approach to understanding Brownian motion as related to clinical trials.

Many advances have been made in the field of thermoregulation in the past few years. These include our understanding of Fever, which is now considered not simply a rise in deep body temperature foHowing infection, but just one aspect, though perhaps the most easily measured, of the Acute Phase of the Immune Response. Classification and identification of the Cytokines and the availability of recombinant material has greatly aided this research. Similarly, our understanding of the Hypothalamo-Pituitary Adrenal Axis has altered our way of thinking about temperature regulation. Of importance are the problems associated with adverse climatic conditions and survival, and the problems encountered by the neonate and the hibernator. At the biochemical level, our knowledge of the control of heat production and the role of brown adipose tissue is rapidly advancing. All these issues and many others were discussed at a Symposium 'Thermal Physiology 1993' held in Aberdeen, Scotland in August 1993 under the auspices of the Thermal Physiology Commission of the International Union of Physiological Sciences. Six main aspects of the subject of temperature regulation are included in this book, namely, Fever (including the Acute Phase of the Immune Response and Thermoregulatory Peptides), Neurophysiology of Thermoregulation, Neonatal Thermoregulation, Mechanisms of Heat Production, Ecological and Behavioural Thermoregulation, and Emerging Themes in Thermoregulation.

Epigenetic modification of cellular genomes is a fascinating means of regulating tissue- and cell type-specific gene expression in all developmental stages of the life of an organism. Carefully orchestrated processes, such as DNA methylation and a plenitude of specific histone modifications secure the faithful transmission of gene expression patterns to progeny cells. Upon chronic infection, the epigenetic cellular balance can become disrupted and, in the long run, through the epigenetic reprogramming of host cell genomes, contribute to the malignant conversion of formerly healthy cells, in many cases preceded by the establishment of an epigenetic field of cancerization. The present volume undertakes to highlight the interactions of infectious pathogens and their effector molecules with the epigenetic regulatory machinery of the cell. Clearly, the recent take-off of epigenetics research did not leave Research on Infectious Diseases and Infection-Associated Cancer untouched. This resulted in a great many of clinically relevant data on understanding the molecular mechanisms of chronic infectious disease. Infectious pathogen- and disease-specific epigenetic alterations are already being used for the early detection of malignant disease and for the prediction of chemotherapy resistance or response to treatment.

This book, written for pulmonary and family doctors, general practitioners, allergologists, and neuropsychologists, presents cutting-edge clinical research and therapy-oriented knowledge in the field of respiratory medicine. Clinical knowledge is undergoing dramatic improvement. Respiration is one such prominent field. A better understanding of the pathogenesis of respiratory ailments and the regulation of lung ventilation is essential for advances in pharmacotherapy and the patient's quality of life. The book discusses a wide scope of topics, notably, innovations in detection and management of chronic inflammatory conditions such as COPD or asthma, acute infections of the respiratory tract, airway allergies and hyper-responsiveness, lung cancer, interstitial lung diseases, pulmonary function in health, disease and aging, sleep disordered breathing, interaction between the respiratory system and other bodily functions, and psychosomatic aspects of disease. After all, respiration is generated and integrated by the brain; therefore brain function is influential in respiratory regulation. The book is a platform that fosters the exchange of new clinical data between clinicians and academic neuroscientists, bringing a unique blend of medical diagnosis and practice to the leadership in respiratory medicine.

This volume is based on the Workshop on Systems Biology of Tumor Dormancy meeting, held July 25th to July 28th, 2011. The first annual CCSB workshop brought together biologists, clinicians, mathematicians, and computer scientists to discuss various aspects of tumor dormancy and develop novel mathematical/computational models with the keynote speakers. Specific topics included the angiogenic switch, immune system interactions, cancer stem cells and signaling.

Cell culture based research is important for our understanding of biological processes at the cellular and molecular level. Using this approach, the previous decades have produced a wealth of mechanistic information in all areas of biomedical research. Such in vitro research, however, lacks the complexity of in vivo investigations, where many different cell types interact with each other in a normal, three-dimensional environment, with normal levels of cytokines and growth factors. Furthermore, complex human diseases, such as cancer, diabetes or chronic inflammation, can only be modeled in vivo. Due to its small size, its short reproduction time, and the possibility to introduce specific gene mutations, the mouse has become the favourite mammalian model organism to study in vivo function of genes during development and in disease. This book combines review articles on selected subjects presented at the symposium "Mouse as a Model Organism - From Animals to Cells", held in Rovaniemi, Finland, 2009. Among other topics, high-throughput phenotyping of mouse mutants, mouse phenotypes dependent on nature and nuture, and a spectrum of in vivo, ex vivo and in vitro methods to study cancer in mice are described. This book will give an excellent introduction to scientists interested in the use of mice as a model to understand complex biological questions in the post-genomic era. It will highlight the possibilities, but also discuss the current problems and shortcomings, to give a realistic view of the current state-of-art in this fascinating field of biomedical research.

Twenty years have elapsed since cytoplasmic proteins exhibiting high-affinity binding of long-chain fatty acids were first identified (Ockner et al., Science 177:56-58, 1972). These cellular fatty acid-binding proteins (FABPs) are now well established to comprise a ligand-defined group of macromolecules belonging to a family of cytoplasmic lipid binding proteins. Unique features of the FABPs are the existence of distinct types of FABP and that these are found in a variety of tissues in remarkable abundance, with some cells expressing more than one type. The physiological significance of the FABPs has only partly been elucidated. By increasing the cytoplasmic solubilization of fatty acids, the cellular FABPs are considered to function primarily in intracellular fatty acid transport, but may also be assigned important regulatory roles in cellular lipid homeostasis as well as in the modulation of cell growth and differentiation. The broad interests in cellular FABPs has led to the organization of the 1st International Workshop on Fatty Acid-Binding Protein, held in Maastricht, the Netherlands, in 1989. Prompted by the success of the first meeting, the 2nd International Workshop on Fatty-Acid-Binding Proteins, which was held again in Maastricht, on August 31 and September 1, 1992, brought together scientific scpecialists in the field of FABP research for two days of intensive and fruitful discussion. This volume is a collection of selected papers from this conference, and thus provides the state-of-the-art knowledge of cellular FABPs. The contributors to this issue represent pioneering as well as new investigators, and also reflect the multidisciplinary nature of research in this exciting and rapidly progressing field.

Cardiovascular disease is the major cause of morbidity and mortality worldwide. While the past 40 years have brought major progress in cardiac valve repair and replacement, there remain large patient populations that do not receive such therapies. This, in turn, implies a great need for future basic, applied, and clinical research and, ultimately, therapeutic developments. Heart Valves is a state-of-the-art handbook dedicated to: 1) cardiac valve anatomy, 2) models for testing and research methods; 3) clinical trials; and 4) clinical needs and applications.

"Molecular Pharmacognosy" discusses the application of molecular biology in resource science and authentication of traditional Chinese medicine (TCM). This book reviews the latest developments in pharmacognosy, introduces a series of new views and insights, presents the hotspots and focus of the field of study on molecular pharmacognosy, and predicts a new direction of study on the resource science of TCM. Furthermore, the book also provides an open communications platform for the development of molecular pharmacognosy. This book is intended for biomedical scientists and researchers in the fields of molecular biology, traditional medicine and natural pharmaceutics.

Professor Lu-qi Huang is Director of the Collaborating Centre of the World Health Organization for Traditional Medicine (Chinese Materia Medica) and Vice-Chairman of the Australia Chinese Association for Biomedical Sciences Inc.

Computational modeling is emerging as a powerful new approach to study and manipulate biological systems. Multiple methods have been developed to model, visualize, and rationally alter systems at various length scales, starting from molecular modeling and design at atomic resolution to cellular pathways modeling and analysis. Higher time and length scale processes, such as molecular evolution, have also greatly benefited from new breeds of computational approaches. This book provides an overview of the established computational methods used for modeling biologically and medically relevant systems.