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This volume is a concise yet comprehensive resource for physicians dealing with, and interested in, the field of molecular pathology in dermatopathology. The book includes descriptions of the techniques and their application to cutaneous diseases and describes possible future techniques and their use in dermatopathology. Special emphasis is also given to the practical application of these techniques to particular situations illustrated by demonstrative cases.Written by experts in their fields, Precision Molecular Pathology of Dermatologic Diseases is of great value to pathologists, dermatologists, resident and fellows, internists, and general practitioners who deal with dermatologic diseases.

Genomic Applications in Pathology provides a state-of-the art review of the scientific principles underlying next generation genomic technologies and the required bioinformatics approaches to analyses of the daunting amount of data generated by current and emerging genomic technologies. Implementation roadmaps for various clinical assays such as single gene, gene panels, whole exome and whole genome assays are discussed together with issues related to reporting, including the pathologist's role in interpretation and clinical integration of genomic tests results. Genomic applications for site-specific solid tumors and hematologic neoplasms are detailed, as well as genomic applications in pharmacogenomics, inherited genetic diseases, and infectious diseases. The latest iteration of practice recommendations and guidelines in genomic testing, put forth by stakeholder professional organizations such as the Association for Molecular Pathology and the College of American Pathologists, are also discussed in the volume, as well as regulatory issues and laboratory accreditation related to genomic testing.Written by experts in the field, Genomic Applications in Pathology provides a comprehensive resource that is of great value to practicing molecular pathologists, hematopathologists, other subspecialized pathologists, general pathologists, pathology trainees, oncologists, and geneticists.​

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.

Having last year published “Up from Clinical Epidemiology & EBM” and also “Epidemiological Research: Terms and Concepts,” Miettinen now – this time with collaboration from his junior colleague I. Karp – brings out this further introduction into epidemiological research; and he is now working on an introduction into clinical research, for publication next year. It evidently is Miettinen's felt time to crystallize the basic understandings he has come to as the culmination of a half-century of concentrated effort to advance the theory of epidemiological and ‘meta-epidemiological clinical'research. In accord with its title, this book focuses on research to develop the knowledge-base for preventive medicine, which mainly is knowledge about the causal origin –etilogy, etiogenesis – of illness. It first illustrates how wanting this knowledge still is, despite much research; and it then aims to guide the reader to more productive etiogenetic research. This book places much emphasis on the need to assure relevance by principles-guided objects design for the studies, which now remains conspicuously absent from epidemiologists'concerns. And as for methods design, this book exposes the fallacies in the still-common ‘cohort'and ‘case-control'studies, defines the essentials of all etiogenetic studies, and then addresses the true options for design in this framework of shared essentials. A good deal of attention is also given to the still commonly-held, very major, twin fallacies that screening for an illness is a preventive intervention, to be studied by randomized trials, and that research on it can imply rational guidelines orrecommendations regarding decisions about the screening. While Miettinen already is regarded as ‘the father of modern epidemiology,'he now appears to have become the father also of post-modern epidemiology, where ‘epidemiology'still means epidemiological research.

This book provides a state-of-the-art approach to the molecular basis of hematologic diseases and its translation into improved diagnostics and novel therapeutic strategies. Several representative hemato-oncologic malignancies are analyzed in detail: acute lymphoblastic leukemia, acute myeloid leukemia, B-cell Non-Hodgkin lymphomas, multiple myeloma, chronic lymphocytic leukemia, chronic myeloid leukemia, myelodysplastic syndromes, and myeloproliferative neoplasms. Experts in the field describe the molecular methods applied for modern diagnostics and therapies, such as hematopoietic stem cell transplantation, donor recipient matching, banking of biological material, analyses of post-transplant chimerism, and minimal residual disease monitoring. The volume concludes with an extensive section comprising thorough step-by-step protocols of molecular techniques in hematology, all of them validated in the authors'own laboratories.

Physical implementation of the memristor at industrial scale sparked the interest from various disciplines, ranging from physics, nanotechnology, electrical engineering, neuroscience, to intelligent robotics. As any promising new technology, it has raised hopes and questions; it is an extremely challenging task to live up to the high expectations and to devise revolutionary and feasible future applications for memristive devices. The possibility of gathering prominent scientists in the heart of the Silicon Valley given by the 2011 International Joint Conference on Neural Networks held in San Jose, CA, has offered us the unique opportunity of organizing a series of special events on the present status and future perspectives in neuromorphic memristor science. This book presents a selection of the remarkable contributions given by the leaders of the field and it may serve as inspiration and future reference to all researchers that want to explore the extraordinary possibilities given bythis revolutionary concept.

Lactoferrin is an iron-binding glycoprotein belonging to the transferrin family. It acts as a defense in host animals against microbes and viruses, since it has a broad spectrum of antimicrobial and antiviral activities. Lactoferrin has been shown to regulate the growth and differentiation of many types of cells. The results of recent studies indicate that lactoferrin is a potent regulator of dermal fibroblasts, and promotes cutaneous wound healing. The collagen gel contraction, a model of wound contraction during wound healing process, and migration of human fibroblasts were enhanced by lactoferrin. LRP-1 (LDL Receptor related Protein-1) acts as a signaling receptor for lactoferrin that mediate fibroblast response to lactoferrin by activating ERK/MAPK signaling pathway. In addition, lactoferrin promotes biosynthesis of extracellular matrix (ECM) component such as type-I collagen and hyaluronan. Hyaluronan is a major component of ECM in connective tissue and promotes wound healing. The promoting effect of lactoferrin on hyaluronan production was accompanied by promotion of HAS2 (hyaluronan synthase 2) expression. These observations suggest that lactoferrin promotes the wound healing by providing an ECM that promotes fibroblast migration. Lactoferrin is also known for its anti-inflammatory and immune modulating properties. According to recent in vivo study, lactoferrin promotes wound repair by promoting the early inflammatory phase of wound healing. Based on this, recombinant human lactoferrin was subsequently tested clinically in a Phase II trial in patients with diabetic ulcers and was found to be effective. Lactoferrin should be further evaluated in patients with diabetic and other types of ulcers.

The mouse is a perfect model organism to study mammalian, and thus indirectly also human, embryology. Most scientific achievements that have had an important impact on the understanding of basic mechanisms governing embryo development in humans, originated from mouse embryology. Stem cell research, which now offers the promise of regenerative medicine, began with the isolation and culture of mouse embryonic stem cells by Martin Evans (who received the Nobel Prize in medicine in 2007 for this achievement) and Matthew Kaufman. This book provides an overview of mouse development, spanning from oocytes before fertilization to the state-of-the-art description of embryonic and adult stem cells. The chapters, written by the leading specialists in the field, deal with the most recent discoveries in this extremely fast-developing area of research.

Our recent understanding of the cellular and molecular defects and the regulation of the apoptotic signalling pathways has resulted in rationally designed anticancer strategies and the development of novel agents that regulates apoptosis. A comprehensive review of all apoptotic-related anticancer therapies is not the purpose of this book. However, in the volume of this book with 11 chapters, we have described a number of novel apoptotic regulators that have shown promising value and also great feasibility for cancer treatment. These novel agents either occur naturally or are chemically synthesized. While we are excited about the discovery and development of these novel apoptotic regulators as potential anticancer agents, a degree of caution should be always borne in mind when interpreting the success of preclinical pro-apoptotic candidates since potential problems inevitably lie ahead. These problems usually include target specificity, unanticipated toxicity, compound stability, formulation issues, pharmacokinetic and pharmacodynamic profiles. Nevertheless, we believe that this collection of 11 chapters by established leaders in the area of apoptosis will be of great interest to not only academics working in the field of cancer research and apoptosis but also pharmaceutical and pharmacological industries that. We are looking forward to the further development to push these potential agents toward clinical stage.

The book aims to introduce the reader to the emerging field of Evolutionary Systems Biology, which approaches classical systems biology questions within an evolutionary framework. An evolutionary approach might allow understanding the significance of observed diversity, uncover “evolutionary design principles” and extend predictions made in model organisms to others. In addition, evolutionary systems biology can generate new insights into the adaptive landscape by combining molecular systems biology models and evolutionary simulations. This insight can enable the development of more detailed mechanistic evolutionary hypotheses.

Medical research involving human subjects has contributed to considerable advancements in our knowledge, and to medical benefits. At the same time the development of new technologies as well as further globalisation of medical research raises questions that require the attention of researchers from a range of disciplines. This book gathers the contributions of researchers from nine different countries, who analyse recent developments in medical research from ethical, historical, legal and socio-cultural perspectives. In addition to reflections on innovations in science such as genetic databases and the concept of “targeted therapy” the book also includes analyses regarding the ethico-legal regulation of new technologies such as human tissue banking or the handling of genetic information potentially relevant for participants in medical research. Country and culture-specific aspects that are relevant to human medical research from a global perspective also play a part. The value of multi- and interdisciplinary analysis that includes the perspectives of scholars from normative and empirical disciplines is a shared premise of each contribution.

Mitochondria are far more than the “powerhouse” of the cell as they have classically been described. In fact, mitochondria biological activities have progressively expanded to include not only various bioenergetic processes but also important biosynthetic pathways, calcium homeostasis and thermogenesis, cell death by apoptosis, several different signal transduction pathways mainly related to redox control of gene expression and so on. This functional and structural complexity may undergo important derangements so to justify the definition of ‘mitochondrial medicine', which should include all the clinical consequences of congenital or acquired mitochondrial dysfunctions. There are actually a growing number of studies which assign a significant pathogenic role to damaged mitochondria in different diseases: ischemia/reperfusion injury, neurodegenerative diseases, cancer with its dramatic sequelae (i.e, metastasis), metabolic syndrome, hyperlipidemias, just to mention a few of the most important pathologies. In this context, a further aspect that should not be disregarded is the interaction of pharmacological agents with mitochondria, not only in regard of the toxicological aspects but, above all, of the potential therapeutic applications. In fact, it is interesting to note that, while the properties of different so-called “mitoxicants” are well-known, the subtle linkages between drugs and mitochondria is still in need of a real pharmacological and therapeutic control at the clinical level. This lack of consideration can often lead to an underestimation of unwanted toxic effects but also of desirable therapeutic activities. A reevaluation of the potential clinical role of mitochondria could give a new light on some yet obscure aspects of human pathophysiology.

This atlas will illustrate the distribution and morphological features of interstitial cells of Cajal (ICC) which are the key cells to understanding of the regulatory mechanism of gastrointestinal motility, since ICC act as both pacemaker and as intermediates in neural transmission, and since ICC show specific distribution patterns depending on their anatomical positions. All subtypes of ICC located in the different tissue layers and different levels of the gastrointestinal tract will be revealed by immunohistochemistry for Kit receptors and nerves by using mainly whole-mount stretch preparation of the guinea-pig tissues. Three-dimensional reconstruction of confocal images will particularly help the readers to understand the peculiar arrangement of ICC networks in situ and the correlation between ICC and nerves. Electron micrographs will help illustrate the characteristic features of ICC and their ultrastructural differences from fibroblasts, smooth muscles and other interstitial cells.

It is generally accepted that neuropsychiatric disorders have a biological basis. Pathological changes leading to illness have been confirmed for Alzheimer's (amyloid plaques) and Parkinson's disease (loss of dopaminergic transmission) and are the foundation for studies on the molecular biology of these disorders. For other neuropsychiatric disorders, in particular for schizophrenic and affective disorders, molecular causes appear to be more complex and therefore remain hypothetical, despite decades of research. Changes in a number of neuronal pathways and structures have been reported to be associated with these disorders and are currently under extensive investigation. The present volume reviews recent knowledge with emphasis on ongoing research findings. Current hypotheses based on these findings are described and discussed.

Nanotechnology is a collective term describing a broad range of relatively novel topics. Scale is the main unifying theme, with nanotechnology being concerned with matter on the nanometer scale. A quintessential tenet of nanotechnology is the precise self-assembly of nanometer-sized components into ordered devices. Nanotechnology seeks to mimic what nature has achieved, with precision at the nanometer level down to the atomic level. Nanobiotechnology, a division of nanotechnology, involves the exploitation of biomaterials, devices or methodologies in the nanoscale. In recent years a set of b- molecules has been studied and utilized. Virus particles are natural nanomaterials and have recently received attention for their tremendous potential in this field. The extensive study of viruses as pathogens has yielded detailed knowledge about their biological, genetic, and physical properties. Bacterial viruses (bacte- ophages), plant and animal eukaryotic viruses, and viruses of archaea have all been characterized in this manner. The knowledge of their replicative cycles allows manipulation and tailoring of particles, relying on the principles of self-assembly in infected hosts to build the base materials. The atomic resolution of the virion structure reveals ways in which to tailor particles for higher-order functions and assemblies.

This fascinating book encourages many microbiologists and students to enter the new world of signal transduction in microbiology. Over the past decade, a vast amount of exciting new information on the signal transduction pathway in bacteria has been unearthed.

influence on the conclusions that result. A very “conservative” statistic requires very strong proof to demonstrate significant differences, whereas a “liberal” one requires less. “Yuck,” you say already, “I just want to know the answer. ” To this, I respond, when in doubt, use a conventional statistical method, one that can be agreed on and accepted by most authorities. These conventional kinds of methods will be presented in this book. As you gain experience, choosing statistical methods will become almost an intuitive process. For example, for problems in which you have little experience, you will be very cautious and conservative. By analogy, this is similar to rafting a river for the first time. If you see rapids in the river, you will be more conservative as you approach them – wearing a life jacket and helmet, and using your paddle to avoid rocks – at least until you have expe- enced them and developed confidence. You will tend to be more liberal when near a sandy shore in clear, calm, shallow water. For experiments in microbiology in which you have much experience, your microbiological knowledge enables you to be more statistically liberal, as you will know whether the result of statistical analysis is microbiologically rational. Finally, statistics is not an end-all to finding answers. It is an aid in research, quality control, or diagnostic processes to support critical thinking and decisi- making.

Recent advances in the biosciences have led to a range of powerful new technologies, particularly nucleic acid, protein and cell-based methodologies. The most recent insights have come to affect how scientists investigate and define cellular processes at the molecular level. Molecular Biomethods Handbook, 2nd Edition expands upon the techniques included in the first edition, providing theory, outlines of practical procedures, and applications for a range of techniques. Part A of the book describes nucleic acid methods, such as gene expression profiling, microarray analysis and quantitative PCR. In Part B, protein and cell-based methods are outlined, in subjects ranging from protein engineering to high throughput screening. Written by a well-established panel of research scientists, Molecular Biomethods Handbook, 2nd Edition provides an up to date collection of methods used regularly in the authors'own research programs. This book will prove to be an invaluable reference for those engaged in or entering the field of molecular biology, and will provide the necessary background for those interested in setting up and using the latest molecular techniques.

The complexarchitectureofneuronal networks togetherwith the extraordinary associated functions make the nervous system a fascinating biological structure. The considerable work performed to explore this cellular machinery is nowadays successfulbecause the mysteryofnervous system developmentisbeing unravelled. As described in their outstanding review published 10 years ago in Science.'Marc Tessier-Lavigne and Corey Goodman-the pioneers of the molecular era of axon guidance-summarized the assembly of nervous system connections as a subtle game of attraction and repulsion of neuronal growth cones. The cellular ballet ensuring the formation of billions of synapses, which ultimately gives rise to the highest cognitive functions, is primarily orchestrated by a step-by-step mechanism of growth driven by multiple molecular cues. While our general concept of axon guidance remains identical, a profound evolution ofour knowledge ofthe molecular identityofthe guidance cues together with their interactions and signalling pathways occurred over the past ten years. This book proposes an exhaustive and updated view ofthe current knowledge ofthe molecular and cellular mechanisms ensuring axon growth and guidance. An introductory chapterby C. Bouquetand F.Nothias will remind the readers ofall the features ofa growth cone and the mechanisms controlling its growth. From there, one enters a fabulous journey with a growth cone, a Tom Thumb story filled with molecular encounters and complex interactions leading to one ofthe most fantastic developmental achievements: the nervous system wiring.

One of the most challenging issues for clinical trial investigators, sponsors, and regulatory officials is the interpretation of experimental results that are composed of the results of multiple statistical analyses. These analyses may include the effect of therapy on multiple endpoints, the assessment of a subgroup analysis, and the evaluation of a dose-response relationship in complex mixtures. Multiple Analyses in Clinical Trials: Fundamentals for Clinical Investigators is an essentially nonmathematical discussion of the problems posed by the execution of multiple analyses in clinical trials. It concentrates on the rationale for the analyses, the difficulties posed by their interpretation, easily understood solutions, and useful problem sets. This text will help clinical investigators understand multiple analysis procedures and the key issues when designing their own work or reviewing the research of others. This book is written for advanced medical students, clinical investigators at all levels, research groups within the pharmaceutical industry, regulators at the local, state, and federal level, and biostatisticians. Only a basic background in health care and introductory statistics is required. Dr. Lemuel A. Moyé, M.D., Ph.D. is a physician and Professor of Biometry at the University of Texas School of Public Health. He has been Co-Principal Investigator of two multinational clinical trials examining the role of innovative therapy in post myocardial infarction survival (SAVE) and the use of cholesterol reducing agents in post myocardial infarction survival in patients with normal cholesterol levels (CARE). He has authored over one hundred articles in journals such as the Journal of the American Medical Association, the New England Journal of Medicine, Statistics in Medicine, and Controlled Clinical Trials. From the reviews: From the reviews:'A quick scan of the book indicates that it is not a typical statistics book…You can jumpin almost anywhere and just start reading…I like the book's organization. There is a chapter on clinical trials. Then there are several chapters that explain the situations that arise from the occurrence of multiple analyses. Particular emphasis is given to multiple endpoints, situations where one continues a study to follow up on unanticipated results, and to subgroup analyses, interventions that impact only a fraction of the subjects in a study. The author is equally adept at describing clinical trials for the statistician as at explaining statistics to the clinical investigator. I enjoyed leafing through this book and would certainly enjoy have the opportunity to sit down and read it.'Technometrics, August 2004'Moyé's background as a statistician and MD makes him especially qualified to write this book…The clinical trial examples are a major strength of the book…His medical background and extensive clinical trials experience shine through.'Statistics in Medicine, 2004, 23:3551-3559'The many examples from well known clinical trials are clearly one of the strengths of this book. It is also fascinating to share the author's experience with the FDA where he attended many meetings of Advisory Committees.'Biometrics, December 2005'According to the preface, this book is written for clinical investigators and research groups within the pharmaceutical industry, medical students and regulators. … I admire the eloquency of the author. … The author does a remarkable job …. Without any doubt, the book is a valuable source of ideas for the intended audience. For statisticians it is an interesting source of experimental setups, that are actually used in practice and that consequently are worth while to be studied.'(dr H. W. M. Hendriks, Kwantitatieve Methoden, Issue 72B41, 2005)'The book is entertaining and informative, sufficiently informal to recruit and retain the intended non-statisticalreadership, but sufficiently for