view, showing that multiple molecular pathways must be affected for cancer to develop, but with different specific proteins in each pathway mutated or differentially expressed in a given tumor (The Cancer Genome Atlas Research Network 2008; Parsons et al. 2008). Different studies demonstrated that while widespread mutations exist in cancer, not all mutations drive cancer development (Lin et al. 2007). This suggests a need to target only a deleterious subset of aberrant proteins, since any tre- ment must aim to improve health to justify its potential side effects. Treatment for cancer must become highly individualized, focusing on the specific aberrant driver proteins in an individual. This drives a need for informatics in cancer far beyond the need in other diseases. For instance, routine treatment with statins has become widespread for minimizing heart disease, with most patients responding to standard doses (Wilt et al. 2004). In contrast, standard treatment for cancer must become tailored to the molecular phenotype of an individual tumor, with each patient receiving a different combination of therapeutics aimed at the specific aberrant proteins driving the cancer. Tracking the aberrations that drive cancers, identifying biomarkers unique to each individual for molecular-level di- nosis and treatment response, monitoring adverse events and complex dosing schedules, and providing annotated molecular data for ongoing research to improve treatments comprise a major biomedical informatics need.

This book provides a snapshot of the state-of-the art in the study of mammalian cell nuclear architecture, and features a diverse range of chapters written by top researchers. A key aspect is an emphasis on precise and repeatable quantitative analysis and simulation in addition to the more familiar biological perspective. The fusion of such material frames the future of the discipline. Quantitative contributions stress reproducible and robust 3D analysis, using a variety of tools ranging from point pattern analysis to shape registration methods. Biological insights include the role of nuclear subdomains in cancer, nuclear molecular motors, and a holistic view of gene transcription.

The idea that the microbial communities within the GI tract have a profound influence on general human health actually originated with Russian scientist Elie Metchnikov at the turn ofthe last century. Also known as the "fatherofimmunol- ogy", Metchnikovbelievedthat putrefactivebacteriain the gut were responsible for enhancing the aging process. He theorized that ingestion ofhealthy bacteria found in fermented foods could counteract toxic bacteria and was the key to good health. His theories concerning good bacteria and health can be found in his treatise "The ProlongationofLife: Optimistic Studies".Thesewritings promptedJapanesescientist Minoru Shirotatobegin investigationofhow fermentative bacteriaimprove health. He succeededin isolating astrainofLactobacillusthat could survive passage through the intestine, while promoting a healthy balance ofmicrobes. The "Shirota strain" is still used today in the fermented beverage Yakult.It is clear from a commercial standpoint that these ideas have inspired the development of a probiotic industry, which has expanded greatly in the U.S. over the past 5-10 years.

Kisspeptin has been shown to be both necessary and sufficient for activation of the reproductive axis, during puberty and later in adulthood. This makes kisspeptin a fundamental component of the reproductive axis. Kisspeptin has been deemed the single most potent stimulator of GnRH neurons yet known. The importance of kisspeptin has been documented in humans as well as non-human animal models, ranging from monkeys, sheep, and rodents to numerous fish species, thus signifying a highly conserved nature of its reproductive function. Importantly, kisspeptin neurons seem to mediate many of the regulatory effects of other signals, whether they are metabolic, circadian, hormonal, or stress. This places kisspeptin neurons in a unique position to be key nodal points and conduits for conveying numerous endogenous and exogenous signals to the reproductive axis.

As the first primer on the effects of exercise on human hypertension, Effects of Exercise on Hypertension: From Cells to Physiological Systems provides the state-of-the-art effects of exercise on the many possible mechanisms underlying essential hypertension in humans. The book contains chapters by distinguished experts on the effects of exercise on physiological systems known to be involved in hypertension development and maintenance as well as less well known aspects of hypertension such as 24-hour ambulatory blood pressure profile and oxidative stress. An emerging area, the effects of resistance exercise training on blood pressure is also covered. A unique aspect of the book is that it covers the effects of exercise mimetics on vascular cell adaptations in order to begin to elucidate some of the cellular mechanisms that may underlie blood pressure reductions with exercise training. Lastly, the book will end with a chapter on the interactive effects of genes and exercise on blood pressure. Chapters are grouped by physiological system or mechanism. The text begins with two overview chapters; one on the general effects of aerobic exercise training and the second on the general effects of resistance exercise training on blood pressure. Each chapter begins with a bulleted list of key points. Effects of Exercise on Hypertension: From Cells to Physiological Systems will be of great value to professional individuals in cardiovascular medicine, the cardiovascular sciences, allied health care professionals, and medical and graduate students in the cardiovascular sciences and medicine.

Protein conversion from a water-soluble native conformation to the insoluble aggregates and fibrils, which can deposit in amyloid plaques, underlies more than 20 human diseases, representing a major public health problem and a scientific challenge. Such a conversion is called protein misfolding. Protein misfolding can also involve errors in the topology of the folded proteins and their assembly in lipid membranes. Lipids are found in nearly all amyloid deposits in vivo, and can critically influence protein misfolding in vitro and in vivo in many different ways. This book focuses on recent advances in our understanding of the role of lipids in modulating the misfolding of various proteins. The main emphasis is on the basic biophysical studies that address molecular basis of protein misfolding and amyloid formation, and the role of lipids in this complex process.

Clinical Mycology offers a comprehensive review of this discipline. Organized by types of fungi, this volume covers microbiologic, epidemiologic and demographic aspects of fungal infections as well as diagnostic, clinical, therapeutic, and preventive approaches. Special patient populations are also detailed.

Stem cells are fascinating cell types. They can replicate themselves forever while retaining the potential to generate progeny with speci?c functions. Because of these special properties, stem cells have been subjects of intensive investigation, from understanding basic mechanisms underlying tissue generation, to modeling human diseases, to application for cell replacement therapy. Stem cells come in different forms. For example, mouse embryonic stem cells can general all cell types in a body, either in a dish or when put back into mouse embryos. On the other hand, neural stem cells in the adult brain generate neurons and glia cells that contribute to the brain's plasticity. Rapid progress has been made in the stem cell ?eld with discov- ies published in a record speed. A quick Pubmed search has returned 2789 hits for "embryonic stem cells" and 815 hits for "adult neural stem cells/neurogenesis" in the year 2008 alone. It remains a taunting task for all who are interested in stem cells to keep up with rapidly accumulating literatures. The "Perspectives of Stem Cells" by a truly international team of experts provides a timely and invaluable highlight of the stem cell ?eld gearing toward future therapeutic applications in the nervous system. Stem cells with neural potentials have attracted a lot of attention because of their promise for cell replacement therapy, ranging from degenerative neurological dis- ders to spinal cord injuries.

Sustainable Biotechnology; Sources of Renewable Energy draws on the vast body of knowledge about renewable resources for biofuel research, with the aim to bridge the technology gap and focus on critical aspects of lignocellulosic biomolecules and the respective mechanisms regulating their bioconversion to liquid fuels and other value-added products. This book is a collection of outstanding research reports and reviews elucidating several broad-ranging areas of progress and challenges in the utilization of sustainable resources of renewable energy, especially in biofuels.

Folding for the Synapse addresses the current view on how protein folding and misfolding, controlled by molecular chaperones, contribute to synapse function and dysfunction. Molecular chaperones have been studied in relation to de novo protein folding, but there is increasing awareness that chaperone function is required for the regulation of protein dynamics when functioning physiologically as an isolated moiety or part of a protein complex. This book will introduce both important concepts of folding machineries and give examples of the biological relevance of further chaperone functions.

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.

Extremophiles are known to thrive under harsh environmental conditions. Many extremophilic bio-products are already used as life-saving drugs. Recent technological advancements of systems biology have opened the door to explore these organisms anew as sources of products that might prove useful in clinical, environmental and drug development.

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.

How many citizens take part in moral and political decisions concerning the results obtained by the contemporary life sciences? Should they blindly follow skilled demagogues or false and deceptive leaders? Should they adhere to the voice of the majority, or should they take a different decisional path? Deliberative democracy answers these questions, but what is deliberative democracy? Can we really deliberate if we are completely ignorant of the relevant issue? What about ethical or political expertise, is it strictly necessary? Finally, and most significantly, can a deliberative process take place if we ignore the techniques governing it; that is, the techniques required to be minimally skilled in rational argumentation? Giovanni Boniolo goes back to the historical and theoretical foundations of deliberation showing us, with some irony, that deliberation is a matter of competence, and not just a matter of a right to decide. His conclusion might not delight everyone: "anyone who is not sufficiently acquainted with the subject matter or lacks the sufficient deliberative competence ought not be admitted to deliberative discussions. This restriction makes both good deliberation and a proper deliberative democracy possible, otherwise debate degenerates into demagogy and hypocrisy".

Synthetic Biology (SB) is a revolutionary discipline with a vast range of practical applications, but is SB research really based on engineering principles? Does it contributing to the artificial synthesis of life or does it utilise approaches sufficiently advanced to fall outside the scope of biotechnology or metabolic engineering? This volume reviews the development of SB and includes the major milestones of the discipline, the 'top-down' and 'bottom-up' approaches towards the construction of an artificial cell and the development of the "iGEM" competition. We conclude that SB is an emerging field with extraordinary technological potential, but that most research projects actually are an extension of metabolic engineering since the complexity of living organisms, their tight dependence on evolution and our limited knowledge of the interactions between the molecules, actually make life difficult to engineer.

This book covers the complete spectrum of deformable models, its evolution as an imagery field and its use in many biomedical engineering and clinical application disciplines. It includes level sets, PDEs, curve and surface evolution and their applications in biomedical fields covering both static and motion imagery.

High-fidelity chromosomal DNA replication underpins all life on the planet. In humans, there are clear links between chromosome replication defects and genome instability, genetic disease and cancer, making a detailed understanding of the molecular mechanisms of genome duplication vital for future advances in diagnosis and treatment. Building on recent exciting advances in protein structure determination, the book will take the reader on a guided journey through the intricate molecular machinery of eukaryotic chromosome replication and provide an invaluable source of information, ideas and inspiration for all those with an interest in chromosome replication, whether from a basic science, translational biology and medical research perspective.

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.

The growing knowledge on tumor-immune response interactions and on the tumor microenvironment did not translate so far into better control of cancer by anti-tumor vaccination. The percentage of patients who benefited from vaccination strategies is still too small to justify their general use. It is the aim of this book to present an alternative to the conventional approach of developing injected tumor vaccines to activate anti-tumor immunity, which will fight cancer. It is argued that in situ tumor ablation (destruction) that involves tumor antigen release; cross presentation and the release of danger associated molecular patterns (DAMPs) can make the tumor its own cellular vaccine. Tumor ablation methods using chemicals, radiation, photodynamic therapy, cryoablation, high-temperature, radiofrequency, high intensity focused ultrasound, and electric-based ablation have been developed for focal tumors. In this book experts will deal with two main topics: I. What are the principles of the various ablation modalities, and II. How each method affects the tumor cells and their microenvironment, and how these effects are responsible for the induction of specific anti-tumor immunity. The aims of this book are thus: 1. Familiarize the readers with various methods of in situ tumor ablation. 2. Review the literature and stimulate comparisons on the efficacy of different ablation methods for the treatment of tumors of different histotypes. 3. Review the literature on the effects of various ablation methods on systemic and local anti tumor immunity and on other manifestations of the interactions of tumors with their microenvironment. 4. Stimulate comparative studies on the immunostimulatory effects of different ablation modalities.

blends materials, fabrication, and structure issues of developing nanobio devices in a single volume. treats major nanobio application areas such as drug delivery, molecular diagnostics, and imaging. chapters written by the leading researchers in the field.

Drug-related problems in the elderly is intended to serve as a source of information and clinical support in geriatric pharmacotherapy for students as well as all health care professionals, e.g. physicians, nurses and pharmacists. Pharmacotherapy is of great importance to all mankind. Drugs are however powerful and must be handled appropriately. This is especially important for elderly patients. Drug-related problem is not a major subject in most university programmes in medicine or pharmacy. When there is no speci c course, there is often no book covering the topic. In our view, as teachers at various university courses, there has been a shortage of literature that re ects the most important aspects of drug-related problems in the elderly. Medical practitioners, nurses and pharmacists, need to have this knowledge to be able to serve their patients in the best way. This book covers most aspects of drug-related problems in the elderly. With b- ter knowledge of drug-related dif culties and risks we hope that elderly will have fewer drug-related problems and bene t more from their pharmacotherapy.

This volume provides a transdisciplinary and translational review of many of the leading murine models used to study the mechanisms, mediators and biomarkers linking energy balance to cancer. It provides a review of murine models that should be of interest to basic, clinical and applied research investigators as well as nutrition scientists and students that work in cancer prevention, cancer control and treatment. The worldwide obesity pandemic has been extensively studied by epidemiologic and observational studies and even, in some cases, by randomized controlled trials. However, the development and control of obesity, its comorbidities and its impact on cancer usually occurs over such long periods that it is difficult, if not impossible to conduct randomized controlled trials in humans to investigate environmental contributions to obesity, energy balance and their impact on cancer. In contrast, model organisms, especially mice and rats, provide valuable assets for performing these studies under rigorously controlled conditions and in sufficient numbers to provide statistically significant results. In this volume, many of the leading and new murine models used to study the mechanisms and mediators linking cancer with obesity, sleep, exercise, their modification by environment and how they may continue to be used to further elucidate these relations as well as to explore preclinical aspects of prevention and/or therapeutic intervention are considered. This volume provides an important compilation and analysis of major experimental systems and principles for further preclinical research with translational impact on energy balance and cancer.

The aim of molecular diagnostics is preferentially to detect a developing disease before any symptoms appear. There has been a significant increase, fueled by technologies from the human genome project, in the availability of nucleic acid sequence information for all living organisms including bacteria and viruses. When combined with a different type of instrumentation applied, the resulting diagnostics is specific and sensitive. Nucleic acid-based medical diagnosis detects specific DNAs or RNAs from the infecting organism or virus and a specific gene or the expression of a gene associated with a disease. Nucleic acid approaches also stimulate a basic science by opening lines of inquiry that will lead to greater understanding of the molecules at the center of life. One can follow Richard Feynman's famous statement "What I cannot create, I do not understand."

This comprehensive volume explores the latest research on the mechanisms of resistance in cancer cells to CTL-mediated immunotherapy. Chapter topics discuss cell-mediated immunity as the result of cytotoxic T-lymphocytes (CTL) directed specifically against cancer cells. In addition, the volume reviews how CTL mediate the cytotoxic activity, in large part, by the indication of apoptosis; hence, tumor cells develop anti-apoptotic mechanisms and thereby, resist CTL-induced apoptosis. In order for CTL-mediated antitumor immunotherapy to be effective, it is essential that agents directed against the resistant tumor cells sensitized cancer cells for CTL-mediated apoptosis. Examples of such agents discussed in the volume include are HDAC inhibitors, proteasome inhibitors, Bcl-2 family inhibitors, PARP, antibodies, and more.

New Frontiers in Angiogenesis starts with a comprehensive overview of the field and continues with topics that have been minimally explored. The topics deal with dynamics of vasculogenesis using imaging techniques, bone marrow-derived endothelial cell precursors as potential therapeutic tools, regulation of post-angiogenic vessel regression, vascular mimicry, design and construction of artificial vessels, bioengineering of angiogenesis, and lymphangiogenesis recapitulating angiogenesis in health and disease states. Each chapter is written by leading experts of the subjects. It is hoped that this volume will challenge all of us interested in the field of angiogenesis and cardiovascular biology, in particular those in academia and industries, to think "outside the box" and explore angiogenesis from a fresh angle. It is hoped that New Frontiers in Angiogenesis is thought provoking and serve as a road map for discovering new findings to help betterments of human health.