Molecular epidemiology has recently broaden its focuses due to the development of molecular tools but also by incorporating advances of other fields such as mathematical epidemiology, molecular ecology, population genetics and evolution. Facing new risks of emerging and re-emerging infectious diseases that are threats for humans and their livestock, the objectives of molecular epidemiology include: - the development of molecular tools, genotyping and gene expression - the incorporation of concepts and results of population genetics of infectious diseases - the integration of recent advances in theoretical epidemiology and evolutionary ecology of diseases - a better understanding of transmission for the development of risk factors analyses. This book will demonstrate how the latest developments in molecular tools and in epidemiology can be integrated with studies of host-pathogen interactions. Besides a strong theoretical component, there will also be an emphasis on applications in the fields of epidemiology, public health, veterinary medicine, and health ecology. Students and researchers in the fields of epidemiology, animal and human health, evolutionary ecology, parasitology are the main potential readers of the book, as well as a broader audience from veterinary medicine and conservation.

Epigenetic modifications act on DNA and its packaging proteins, the histones, to regulate genome function. Manifest as the heritable methylation of DNA and as post-translational histone modifications, these molecular flags influence the architecture and integrity of the chromosome, the accessibility of DNA to gene regulatory components and the ability of chromatin to interact within nuclear complexes. While a multicellular individual has only one genome, it has multiple epigenomes reflecting the diversity of cell types and their properties at different times of life; in health and in disease. Relationships are emerging between the underlying DNA sequence and dynamic epigenetic states and their consequences,such as the role of RNA interference and non-coding RNA. These integrated approaches go hand-in-hand with studies describing the genomic locations of epigenetic modifications in different cell types at different times. The excitement and curiosity surrounding epigenomics is driven by a growing community of researchers in a burgeoning field and the development of new technologies built on the backbone of genome sequencing projects. Research has shown that the adaptability and vulnerability of epigenetic states has profound effects on natural variation, the response of the genome to its environment and on health and disease. The aim of this volume is not to describe epigenomes, but rather to explore how understanding epigenomes tells us more about how biological systems work and the challenges and approaches taken to accomplish this. These contributions have attempted to integrate epigenomics into our understanding of genomes in wider context, and to communicate some of the wonders of epigenetics illustrated through examples across the biological spectrum.

Several years ago, when the discovery of catalytic RNA was recognized in a public manner,many people asked if new ?elds of therapy would soon be available. Although some tentative positive answers were given,nobody would say with certainty that RNA of various kinds was a truly promising means of altering gene expression. In fact,over the past decade,both our knowledge of RNAs with different functions and the utility of RNA in the inhibition or enhancement of gene expression have occurred with great drama. We proceeded in terms of possible therapeutic tools from RNase P and group I introns through "hammerhead" RNA enzymes, antisense technology, and more recently, to RNAi and its derivatives. A useful practical method of RNA delivery in animals will complete the picture. The diversity of RNA and the varied role of it inside cells and in therapy should be a tremendous challenge for young molecular biologists. This volume will make their task easier. Sidney Altman Sterling Professor of Molecular,Cellular & Devel- mental Biology,Nobel Laureate Department of Molecular,Cellular and Developm- tal Biology Yale University V NGTPR 4/23/05 1:00 PM Page VI VI Foreword Delivery of nucleic acids to cells in an animal remains a challenging problem. It is the major obstacle to success of therapeutic approaches using genes and oli- nucleotides,including siRNAs. Solutions found so far by chemists are satisfactory only for transfection of cells in culture.

v(D)J recombination: for the community of immunologists and developmental biologists, the molecular route by which B and T lymphocytes acquire their unique function of affording adaptive immunity. Yet, for many-from experienced scientists to trainees-it represents a (rather too) sophisticated process whose true insight is excessively demanding. However, when not simplyconsidered as a private ground for a few aficionados, it can be seen as a way of understanding how maturelympho cytes carry on their basic functions. For the group of aficionados-which includes this editor-it is an elegant paradigm featuring many fascinating evolutionary achievements of which the biological world alone has the secret. These include a subtle biochemical principle most likelyhijacked some 470 million years ago from an ancestral gene invader and since then cleverly adapted by jawed vertebrates to precisely cleave and rearrange their antigen receptor (Ig andTCR)loci. This invader would itself have assigned the services of the nonhomologous end joining (NHEJ) DNArepair machinery as well as various DNApolymerases or transferases to work in concert with developmental clues in lymphoid cell lineages to generate an immune repertoire and efficient host surveillance while avoiding autoimmunity. Recently, important new refinements in these systems have emerged, continuing to challenge ourknowledge andbeliefs. These arejust thetopics covered by the senior authors-all established leaders in this field-and their colleagues, whilst writing the various chapters in V(D)J Recombination.

Current molecular understanding of estrogen action has greatly profited from advances in molecular cell biology. These advances, and their implications for clinical use, were discussed by leading researchers from industry and academia during an international symposium held in Berlin, 1-3 March 2006 and are featured in this volume.

Single Subject Designs in Biomedicine draws upon the rich history of single case research within the educational and behavioral research settings and extends the application to the field of biomedicine. Biomedical illustrations are used to demonstrate the processes of designing, implementing, and evaluating a single subject design. Strengths and limitations of various methodologies are presented, along with specific clinical areas of application in which these applications would be appropriate. Statistical and visual techniques for data analysis are also discussed. The breadth and depth of information provided is suitable for medical students in research oriented courses, primary care practitioners and medical specialists seeking to apply methods of evidence practice to improve patient care, and medical researchers who are expanding their methodological expertise to include single subject designs. Increasing awareness of the utility in the single subject design could enhance treatment approach and evaluation both in biomedical research and medical care settings.

This comprehensive volume will serve as a complete guide to the clinical application of computer assisted systems in monitoring central nervous functions both in the OR and ICU. It presents practical guidelines and therapeutic indications for computerized EEG and Somatosensory Evoked Potential (SSEP) monitoring for the experienced user as well as the novice, leading the newcomer step-by-step to a level of advanced monitoring. Basic procedures and data handling are explained in a user-friendly and practical way. The book also describes what cerebral monitoring can do and what its limitations are. In addition, proper selection of the available monitoring devices, set-up procedures, the technique of electrode placement, trouble shooting and data interpretation are fully covered. Various typical cases underline how EEG power spectra and evoked potential changes are interpreted, how they are used in the light of other variables being measured how they can serve to get a deeper insight into the underlying clinical situation. In this respect representative and color illustrated examples further emphasize the link between this book and clinical practice.

The CCN family of genes currently comprises six secreted proteins (designated CCN16 i.e., Cyr61/CCN1; ctgf/CCN2; Nov/CCN3; WISP1/CCN4; WISP2/CCN5, and WISP3/CCN6) showing a strikingly conserved primary structure, with four modules sharing partial identity with IGF binding proteins, Von Willebrand protein, thrombospondin and several matricellular proteins and growth factors. The current view is that CCN proteins modulate signaling pathways that involve regulatory components of the extracellular matrix. As such, they likely act as a central hub in the regulation of mitosis, adhesion, apoptosis, extracellular matrix production, growth arrest and migration of multiple cell types. The 5th international workshop on the CCN family of genes, that was held in Toronto in 2008 brought together scientists from around the world who have an interest in the biological roles of this emerging family of proteins. On an educational point of view, the workshop was a unique place for an efficient diffusion of scientific information. The present book comprises a series of selected manuscripts that are based on the original communications that were presented at the meeting by worldwide leaders in the field of CCN biology. All major aspects of CCN proteins biology in both normal and pathological conditions are covered in this volume, from structure-functions analysis up to the involvement of CCN proteins in complex physiological functions. In addition to reports that support the Yin-Yang concept of CCN proteins driving opposite effects on the same biological process, this book also comprises several contributions that point to CCN proteins as amenable targets for therapeutic manipulation of disease processes. Together with the special issue of Journal of Cell Communication and Signaling in which authors have extended on the original data presented at the meeting, the present Proceedings provide an instant picture and unique update of the state of the art in the CCN field.

The aim of this book is to present a unique compilation of lectures given by international speakers at the Hammersmith Hospital during the recent Meetings in Hepato-Pancreato-Biliary and Transplantation. New therapeutical approaches, advances in oncology and in diagnostic imaging, which reduce the need for invasive techniques and reach an improvement in survival and quality of life in cancer, are considered in this book. Modern literature has been reviewed with special reference to articles of general interest. In the clinical management of patients with liver, bile duct and pancreas diseases, it is important to assess the degree of disturbance and to diagnose the causative insult, and therefore clinical and laboratory methods of assessing each of these pathologies are of high interest. This version is an up-to-date account of diseases of the liver, biliary tract and pancreas, including transplantation, which we trust will be of value for surgeons, physicians and pathologists and also a reference book for medical students.

Myelodysplastic syndromes (MDS) are the most common hematological malignancies involving mostly the elderly population. The major morbidity relates to patients' symptomatic cytopenias.MDS was previously named as "preleukemia " or " smoldering leukemia" as the lack of terminal cells in MDS and because about 25% of all cases progresses into acute myeloid leukemia. According to various reports the annual incidence of MDS ranges widely from 2-12 per 100.000, increasing to 30-50 cases per 100.000 among persons aged 70 or older. It is believed that the true incidence of MDS have been underestimated however it seems to be comparable to that for multiple myeloma and chronic lymphocytic leukemia. In the past decade much progress had been made; we know more on the disease pathology, there is more emphasis on the care and more targeted therapy had been invested. Athors provide updated knowledge in this book on all clinically important aspects of the disease. Hot topics of our days are discussed in chapters by outstanding and well known scientists from all over the world. We would offer this product both for medical students and postgraduates as well as for all who are interested in this very exciting and fast progressing field of hematology. With this work authors should call attention on the disease for decision makers in healt care systems as well.

The potential of stem cells for healing and disease prevention in all fields of medicine is tremendous and has revolutionized the high-tech biomedical research. In this book, many of the most prominent researchers discuss the challenging topics of stem cell engineering, for example: Ethical issues of stem cell research; technological challenges, stem cell growth and differentiation, therapeutic applications, bioreactors and bioprocesses, high throughput and microfluidic screening platforms, stem cell identification and sorting, intercellular signaling and engineered niches, novel approaches for embryonic and adult stem cell growth and differentiation, stem cells and drug discovery, screening platforms. Stem Cell Engineering offers valuable background and reference for both the public and professionals including industrial staffers, faculty, researchers, engineers, students and scientific journalists.

In the last ten years there has been a considerable increase of interest on the notion of the minimal cell. With this term we usually mean a cell-like structure containing the minimal and sufficient number of components to be defined as alive, or at least capable of displaying some of the fundamental functions of a living cell. In fact, when we look at extant living cells we realize that thousands of molecules are organized spatially and functionally in order to realize what we call cellular life. This fact elicits the question whether such huge complexity is a necessary condition for life, or a simpler molecular system can also be defined as alive. Obviously, the concept of minimal cell encompasses entire families of cells, from totally synthetic cells, to semi-synthetic ones, to primitive cell models, to simple biomimetic cellular systems. Typically, in the experimental approach to the construction of minimal the main ingredient is the compartment. Lipid vesicles (liposomes) are used to host simple and complex molecular transformations, from single or multiple enzymic reactions, to polymerase chain reactions, to gene expression. Today this research is seen as part of the broader scenario of synthetic biology but it is rooted in origins of life studies, because the construction of a minimal cell might provide biophysical insights into the origins of primitive cells, and the emergence of life on earth. The volume provides an overview of physical, biochemical and functional studies on minimal cells, with emphasis to experimental approaches. 15 International experts report on their innovative contributions to the construction of minimal cells.

The term hormesis is de?ned as "a process in which exposure to a low dose of a chemical agent or environmental factor that is damaging at higher doses induces an adaptive bene?cial effect on the cell or organism" (Calabrese et al., 2007; Mattson, 2008). To survive and reproduce in harsh competitive environments, organisms and their cellular components have, through evolution, developed molecular mec- nisms to respond adaptively to various hazards or "stressors" that they encounter. Examples of such stressors include chemicals ingested in food and water (metals, phytochemicals, etc.), increased energy expenditure (running, ?ghting, cognitive challenges, etc.), and reduced energy availability (food scarcity), among others. In most cases, the response of the cell or organism to the stressor exhibits a biphasic dose response, with bene?cial/adaptive responses at low doses (improved fu- tion, increased resistance to damage and disease) and adverse/destructive effects (dysfunction, molecular damage, or even death) at high doses. The prevalence of the biphasic (hormetic) dose response characteristic of biological systems merits consideration of hormesis as a fundamental principle of biology.

The term "heavy metals" is used as a group name of toxic metals and metalloids (semimetals) causing contaminations and ecotoxicity. In strict chemical sense the density of heavy metals is higher than 5 g/cm3. From biological point of view as microelements they can be divided into two major groups. a. For their physiological function organisms and cells require essential microelements such as iron, chromium (III), cobalt, copper, manganese, molidenium, zinc. b. The other group of heavy metals is toxic to the health or environment. Of highest concern are the emissions of As, Cd, Co, Cu, Hg, Mn, Ni, Pb, Sn, Tl. The toxicity of heavy metals is well known at organizational level, while less attention has been paid to their cellular effects. This book describes the toxicity of heavy metals on microorganisms, yeast, plant and animal cells. Other chapters of the book deal with their genotoxic, mutagenic and carcinogenic effects. The toxicity of several metals touch upon the aspects of environmental hazard, ecosystems and human health. Among the cellular responses of heavy metals irregularities in cellular mechanisms such as gene expression, protein folding, stress signaling pathways are among the most important ones. The final chapters deal with biosensors and removal of heavy metals. As everybody is eating, drinking and exposed to heavy metals on a daily basis, the spirit of the book will attract a wide audience.

Proteomics is a multifaceted, interdisciplinary field which studies the complexity and dynamics of proteins in biological systems. It combines powerful separation and analytical technology with advanced informatics to understand the function of proteins in the cell and in the body. This book provides a clear conceptual description of each facet of proteomics, describes recent advances in technology and thinking in each area, and provides details of how these have been applied to a variety of biological problems. It is written by expert practitioners in the field, from industry, research institutions, and the clinic. It provides junior and experienced researchers with an invaluable proteomic reference, and gives fascinating glimpses of the future of this dynamic field.

This book is the first to present the mechanism which explains why light is an effective treatment for so many illnesses and diseases. The book not only explains this mechanism, but describes uses for the mechanism, as well as what new work is planned and what changes will be seen in FDA regulations. Extensive papers and coverage on many interesting topics are included.

This book encompasses the exciting developments and challenges in the fast-moving and rapidly expanding research field of single-molecule kinetic analysis of cell signaling that promises to be one of the most significant and exciting areas of biological research for the foreseeable future. Cell signaling is carried out by complicated reaction networks of macromolecules, and single-molecule analyses has already demonstrated its power to unravel complex reaction dynamics in purified systems. To date, most of the published research in the field of single-molecule processes in cells, focus on the dynamic properties (translational movements of the centre of mass) of biological molecules. However, we hope that this book presents as many kinetic analyses of cell signaling as possible. Although single-molecule kinetic analysis of cellular systems is a relatively young field when compared with the analysis of single-molecule movements in cells, this type of analysis is highly important because it directly relates to the molecular functions that control cellular behavior and in the future, single-molecule kinetic analysis will be largely directed towards cellular systems. Thus, we hope that this book will be of interest to all those working in the fields of molecular and cell biology, as well as biophysics and biochemistry.

Quantitative ultrasound (QUS) of bone is a relatively recent research field. The research community is steadily growing, with interdisciplinary branches in acoustics, medical imaging, biomechanics, biomedical engineering, applied mathematics, bone biology and clinical sciences, resulting in significant achievements in new ultrasound technologies to measure bone, as well as models to elucidate the interaction and the propagation of ultrasonic wave in complex bone structures. Hundreds of articles published in specialists journals are accessible from the Web and from electronic libraries. However, no compilation and synthesis of the most recent and significant research exist. The only book on QUS of bone has been published in 1999 at a time when the propagation mechanisms of ultrasound in bone were still largely unknown and the technology was immature. The research community has now reached a critical size, special sessions are organized in major international meetings (e.g., at the World Congress of Biomechanics, the annual meetings of the Acoustical Society of America, International Bone Densitometry Workshop, etc...). Consequently, the time has come for a completely up to date, comprehensive review of the topic. The book will offer the most recent experimental results and theoretical concepts developed so far and is intended for researchers, graduate or undergraduate students, engineers, and clinicians who are involved in the field. The central part of the book covers the physics of ultrasound propagation in bone. Our goal is to give the reader an extensive view of the mathematical and numerical models as an aid to understand the QUS potential and the types of variables that can be determined by QUS in order to characterize bone strength. The propagation of sound in bone is still subject of intensive research. Different models have been proposed (for example, the Biot theory of poroelasticity and the theory of scattering have been used to describe wave propagation in cancellous bone, whereas propagation in cortical bone falls in the scope of guided waves theories). An extensive review of the models has not been published so far. We intend in this book to present in details the models that are used to solve the direct problem and strategies that are currently developed to address the inverse problem. This will include analytical theories and numerical approaches that have grown exponentially in recent years. Most recent experimental findings and technological developments will also be comprehensively reviewed.

Finally - a book that covers all aspects of the illicit use of cocaine, amphetamines, ecstasy and/or designer drugs such as GHB, written by two experts in their field. The use of these drugs remains a continuous threat in health and medical care delivery, and this book will be an essential asset to the physician who may have to face the evaluation of patients whose use of these drugs compromises an effective treatment plan for other health issues. The book has been conceived to fill the void in existing physician reference materials, and provides a comprehensive review of the theoretical knowledge and scope of pharmacotherapy in individuals who are hooked on a psychoactive substance. While detailed scientific information is obtainable in other major articles, the book's straightforward format and style, along with its illustrations, will make for easy reading as emphasis is put on information specifically related to drugs that occur most abused in today's society. The information provided is based on clinical practice rather than pure experimental data, which will give the physician more effective tools useful in their daily practice. Many mechanisms of action of abuse are described in detail and references are provided to direct the reader to further sources for additional information. As a special feature, the book incorporates uncluttered tables and charts, which result in immediate clarification of the mode of action on the central nervous system and the reason for misuse, thus avoiding usual long and fatiguing text in common reference books. The book aims to give the reader a clear and concise plan on what to do when being faced with an overdose situation. A well-organized Table of Contents rapidly leads the reader from general pharmacological issues to the specific overdose syndrome and its management. Additionally, significant emphasis is placed on the practical do's and don'ts for physicians, with special reference to the predictive signs of aberrant drug-related behavior and the identification of the drug diverter by using urine drug screening.

Synthetic biology is becoming one of the most dynamic new fields of biology, with the potential to revolutionize the way we do biotechnology today. By applying the toolbox of engineering disciplines to biology, a whole set of potential applications become possible ranging very widely across scientific and engineering disciplines. Some of the potential benefits of synthetic biology, such as the development of low-cost drugs or the production of chemicals and energy by engineered bacteria are enormous. There are, however, also potential and perceived risks due to deliberate or accidental damage. Also, ethical issues of synthetic biology just start being explored, with hardly any ethicists specifically focusing on the area of synthetic biology. This book will be the first of its kind focusing particularly on the safety, security and ethical concerns and other relevant societal aspects of this new emerging field. The foreseen impact of this book will be to stimulate a debate on these societal issues at an early stage. Past experiences, especially in the field of GM-crops and stem cells, have shown the importance of an early societal debate. The community and informed stakeholders recognize this need, but up to now discussions are fragmentary. This book will be the first comprehensive overview on relevant societal issues of synthetic biology, setting the scene for further important discussions within the scientific community and with civil society.

In Fragile X-Associated Tremor Ataxia Syndrome (FXTAS), the editors present information on all aspects of FXTAS, including clinical features and current supportive management, radiological, psychological, and pathological findings, genotype-phenotype relationships, animal models and basic molecular mechanisms. Genetic counseling issues are also discussed. The book should serve as a resource for professionals in all fields regarding diagnosis, management, and counseling of patients with FXTAS and their families, as well as presenting the molecular basis for disease that may lead to the identification of new markers to predict disease risk and eventually lead to target treatments.

The text features experimental investigations which use a variety of modern methods and theoretical modeling of surface structures and physicochemical processes which occur at solid surfaces. Nanomaterials and Supramolecular Structures: Physics, Chemistry, and Applications is intended for specialists experienced in the fields of Nanochemistry, Nanophysics, Surface Chemistry (and Physics), synthesis of new nanostructural functional materials and their practical applications. It will also prove useful to students, post-graduates, researchers, and lecturers.

Omics is an emerging and exciting area in the field of science and medicine. Numerous promising developments have been elucidated using omics (including genomics, transcriptomics, epigenomics, proteomics, metabolomics, interactomics, cytomics and bioinformatics) in cancer research. The development of high-throughput technologies that permit the solution of deciphering cancer from higher dimensionality will provide a knowledge base which changes the face of cancer understanding and therapeutics. This is the first book to provide such a comprehensive coverage of a rapidly evolving area written by leading experts in the field of omics. It complies and details cutting-edge cancer research that covers the broad advances in the field and its application from cancer-associated gene discovery to drug target validation. It also highlights the potential of using integration approach for cancer research. This unique and timely book provides a thorough overview of developing omics, which will appeal to anyone involved in cancer research. It will be a useful reference book for graduate students of different subjects (medicine, biology, engineering, etc) and senior scientists interested in the fascinating area of advanced technologies in cancer research. Readership: This is a precious book for all types of readers - cancer researchers, oncologists, pathologists, biologists, clinical chemists, pharmacologists, pharmaceutical specialists, biostatisticians, and bioinformaticists who want to expand their knowledge in cancer research.

Pattern Formation in Morphogenesis is a rich source of interesting and challenging mathematical problems. The volume aims at showing how a combination of new discoveries in developmental biology and associated modelling and computational techniques has stimulated or may stimulate relevant advances in the field. Finally it aims at facilitating the process of unfolding a mutual recognition between Biologists and Mathematicians of their complementary skills, to the point where the resulting synergy generates new and novel discoveries. It offers an interdisciplinary interaction space between biologists from embryology, genetics and molecular biology who present their own work in the perspective of the advancement of their specific fields, and mathematicians who propose solutions based on the knowledge grasped from biologists.

The enormous potential of siRNA as a therapeutic has led to an explosion of interest from the scientific community. There has been intense interest from Big Pharma to capitalise on this new technology but the fact remains that delivery is a key determinant in realizing the full clinical potential of RNA interference. There is an urgent need for better delivery methods to take this technology forward. This book addresses the role of different RNAi molecules in cellular processes as rational for diagnostic and therapeutic approaches. This book will cover RNAi therapeutic design to optimize siRNA potency and reduce off-target effects and current delivery technologies to overcome both intracellular and extracellular barriers. The reader will gain an insight into RNA interference from the cellular mechanisms to screening to siRNA design right through to diagnostic and therapeutic applications.