Transporters in Drug Development examines how membrane transporters can be dealt with in academic-industrial drug discovery and pharmaceutical development as well as from a regulatory perspective. The book describes methods and examples of in vitro characterization of single transporters in the intestines, liver and kidneys as well as characterization of substrate overlap between various transporters. Furthermore, probes and biomarkers are suggested for studies of the transporters' impact on the pharmacokinetics of drug substrates/candidates interacting on transporters. The challenges of translating in vitro observed interaction of transporters into in vivo relevance are explored, and the book highlights perspectives of applying targeted proteomics and mechanistic modeling in this process.

Initially believed to be inactive molecules, glycans are now considered essential for life, both under normal and pathological conditions.

This volume of the series "Biology of Extracellular Matrix " reviews the most recent findings on the role of glycans in the development of diseases and the possible therapeutic use of this class of molecules. It shows how the interaction of glycans with growth factors, growth factor binding proteins, extracellular proteases, protease inhibitors, chemokines, morphogens, and adhesive proteins regulates inflammation, infection, cancer, atherosclerosis, thrombosis and embryonic stem cell biology. Furthermore, an extensive survey about the structure and pharmacological effects of unique marine glycosaminoglycans is discussed as well as the possibility of using these glycans as therapeutic agents.

Give your patrons access to the digital content they need Electronic Resources in Medical Libraries is an essential guide to the challenges of acquiring, licensing, and managing the electronic access and use of books and journals. Medical librarians working in a variety of settings, including academic health centers, hospital libraries, and government health associations, provide entry-level, mid-career, and experienced librarians with comprehensive information and advice on dealing with electronic resources. This invaluable resource examines a wide range of issues, including collection development, pricing, open access, licensing, remote access, statistics, publisher liability, and the Semantic Web. As healthcare professionals, researchers, educators, and students rely more and more on digital content, medical libraries spend more and more time dealing with the complexities surrounding the use of e-resources. Electronic Resources in Medical Libraries examines the issues they face everyday, including the shift from print to electronic materials, off-campus and cross-campus access, usage statistics, journal pricing, open-access publishing, licensing, collection development, and much more. Topics addressed in Electronic Resources in Medical Libraries include: how to negotiate consortial packages how to use an electronic resource management (ERM) system how to create a portal to share electronic resources how to consolidate costs and provide wide access how open access affects pricing how to establish and maintain access to licensed e-resources how to develop a combined e-journal Web page how off-campus students interact with a full-service document delivery option for electronic journals how to integrate e-resources into an online catalog how to apply emerging Semantic Web technologies to digital libraries and much more Electronic Resources in Medical Libraries is an invaluable professional guide for medical and academic librarians, and a helpful classroom resource for faculty and students in library schools.

The Hippo signaling pathway is rapidly gaining recognition as an important player in organ size control and tumorigenesis, and many leading scientists are showing increased interest in this growing field and it's relation to cancer. The chapters in this volume cover virtually all aspects of tumor biology, because members of the Hippo Pathway have been associated with numerous well-established cell signaling pathways, just to name a few; Ras, Wnt, TGFbeta and p53. Moreover, Hippo signaling is not solely involved in regulating "classic" tumor characteristics such as cell proliferation, survival and growth, but is also diversely involved in cell-autonomous and non-cell-autonomous differentiation, migration and organ size control. The primary audience are researchers interested in basic science in the areas of tumor suppression, cell cycle and size regulation, development and differentiation.

"Kinetics and Dynamics" on molecular modeling of dynamic processes opens with an introductory overview before discussing approaches to reactivity of small systems in the gas phase. Then it examines studies of systems of increasing complexity up to the dynamics of DNA. This title has interdisciplinary character presenting wherever possible an interplay between the theory and the experiment. It provides basic information as well as the details of theory and examples of its application to experimentalists and theoreticians interested in modeling of dynamic processes in chemical and biochemical systems. All contributing authors are renowned experts in their fields and topics covered in this volume represent the forefront of today s science."

Extracellular purines and pyrimidines (ATP, ADP, UTP and adenosine) are released into the extracellular milieu in response to a variety of stress conditions and act as important regulators of vascular homeostasis. This new book is uniquely focused on the signaling actions of extracellular purines in endothelial cells and the crucial role of extracellular purines in regulation of angiogenesis, vascular tone, cell permeability, wound healing, inflammation and cell-to-cell communication. This book examines the responses of endothelial cells, originating from various tissues (such as cornea, pancreas and uterus), to extracellular nucleotides and adenosine under physiological and pathological conditions, i.e. pregnancy, hypoxia, hypertension, inflammation and diabetes. In the book's 12 chapters, the role of purinergic signaling in endothelium-dependent tissue perfusion, regulation of endothelial barrier function, and angiogenesis are discussed. The mechanisms of ATP release and its role in intercellular communication are also presented. In addition, the book provides the most up to date mechanisms of extracellular nucleotide metabolism by purine-converting ecto-enzymes and their contribution to purinergic signaling in endothelial cells originating from various vascular beds. This book is a valuable resource for biomedical research scientists, clinical scientists, graduate students and health science professionals interested in the mechanisms of extracellular purine function in endothelial cells under physiologic and pathologic conditions.

* Discusses the emerging concepts in mast cell biology * Investigates development, homeostasis, activation of mast cells and their roles in maintaining health * Investigate mast cells' participation in disease The editors of Mast Cell Biology, Drs. Gilfillan and Metcalfe, have enlisted an outstanding group of investigators to discuss the emerging concepts in mast cell biology with respect to development of these cells, their homeostasis, their activation, as well as their roles in maintaining health on the one hand and on the other, their participation in disease.

This volume examines all facets of the complex biology of Immunoglobulin E (IgE) antibodies, which play an essential role in the pathophysiology of allergic diseases and immunity to parasites. It highlights the unique mechanisms involved in the regulation of IgE production at both the molecular and cellular level. Furthermore, it discusses in detail novel findings on how the affinity, specificity and cross-reactivity of IgE can fine-tune mast cell responses to allergens. The book also explores the beneficial roles of IgE antibodies in immunity to helminthes and protection against tumors, and how the properties of IgE-mediated immunity are employed in the development of IgE therapeutic antibodies. All chapters were written by respected experts in their fields and will appeal to scientists and clinicians alike.

The rapidly developing field of systems biology is influencing many aspects of biological research and is expected to transform biomedicine. Some emerging offshoots and specialized branches in systems biology are receiving particular attention and are becoming highly active areas of research. This collection of invited reviews describes some of the latest cutting-edge experimental and computational advances in these emerging sub-fields of systems biology. In particular, this collection focuses on the study of mammalian embryonic stem cells; new technologies involving mass-spectrometry proteomics; single cell measurements; methods for modeling complex stochastic systems; network-based classification algorithms; and the revolutionary emerging field of systems pharmacology.

The three keywords, Orthodontics, Europe and Quality represent the important issues in this book, describing the EURO-QUAL, BIOMED 1 Programme. In this Programme, individuals and representatives of institutions have been asked to contribute to the discussion on the development of a quality system for orthodontic care. The philosophy of Total Quality Management was adopted and specific emphasis was given to patient quality. When considering how the structure and quality of European orthodontic care continuously can be improved, there are certain conditions which are difficult to modify. From the start this has been realised and respected and therefore the guidelines for the quality are flexible and can be adapted to different conditions. Available knowledge has been bundled and an attempt has been made to understand the reality of orthodontic care in Europe: the product and the process.

This third volume in the series Tumor Dormancy, Quiescence, and Senescence discusses the role of tumor dormancy and senescence in a number of diseases, including breast cancer, ovarian cancer and leukemia. The contents are organized under five subheadings: General Applications, Role in Breast Cancer, Role in Ovarian Cancer, Role in Leukemia and Role in Cardiovascular Disease. The first section includes basic information on the definition of dormancy, how cells become senescent and what they do, along with an appraisal of the current state of research on dormancy. Section Two explores dormancy in breast cancer, including the progression of hormone-dependent mammary tumors after dormancy. Section Three details the resistance of Type II ovarian tumors, in which the resistant tumor cell population persists after chemotherapy in a state of dormancy, with recurrent tumors arising upon transformation of such dormant cells back to malignant growth. This section explains how lineage, histological subtypes and grade influence the differential response of ovarian cancer resistance to platinum drugs. The fourth section explores leukemia, discussing regulation of the promyelocytic leukemia protein and its role in premature senescence. The final section explores the role of senescence and autophagy in age-related cardiovascular diseases and the observation that autophagy seems to retard cardiac senescence. Like the two preceding volumes in the series, Volume 3 stands out for its comprehensive approach, its roster of some 26 expert contributors representing seven different countries and its up-to-date review of leading-edge technology and methods.

The field of clinical proteomics has rapidly evolved during the past few years and is continuously growing as new methodologies and technologies emerge. In Clinical Proteomics, a select group of leading researchers has contributed their state-of-the-art methodologies on protein profiling and identification of disease biomarkers in tissues, microdissected cells and body fluids. Experimental approaches involving the application of two-dimensional electrophoresis, multi-dimensional liquid chromatography, SELDI/MALDI mass spectrometry and protein arrays, as well as the bioinformatic and statistical tools pertinent to the analysis of proteomics data, are thoroughly detailed in these readily reproducible methods and protocols, explained through the step-by-step instructional format of the highly successful Methods in Molecular Biology series.

This book is devoted to the graphics of patient data: good graphs enabling straight-forward and intuitive interpretation, efficient creation, and straightforward interpretation. We focus on easy access to graphics of patient data: the intention is to show a large variety of graphs for different phases of drug development, together with a description of what the graph shows, what type of data it uses, and what options there are. The main aim is to provide inspiration in form of a graphics cookbook. Many graphs provide creative ideas about what can be done. The book is not intended to be technical. It introduces general principles of good visualization to make readers understand the concepts, but the main focus is on the creativity and usefulness: readers are enabled to browse through the book to get ideas of how their own data can be analyzed graphically.

For additional information visit Editor s companion website: http: //www.elmo.ch/doc/life-science-graphics/

Sleep has recently been recognized as a critical determinant of energy balance regulating, restoration and repair of many of the physiologic and psychologic processes involved in modulating energy intake and utilization. In addition to having an impact on obesity, sleep abnormalities, both quantitative and qualitative, have now been shown to have significant effects on obesity associated comorbidities, including metabolic syndrome, premalignant lesions and cancer. Sleep problems and fatigue also constitute a significant challenge for the ever expanding group of cancer survivors. Moreover, circadian misalignment, such as that experienced by "shift workers" has been shown to be associated with an increased incidence of several malignancies including, breast, colorectal and prostate cancer, consistent with the increasing recognition of the role of clock genes in the metabolic processes. Of increasing concern is the accelerating incidence of sleep disorders in childhood, their association with childhood obesity and associated abnormalities of circulating cytokines, adipokines and metabolic factors, many of which are implicated as etiologic mediators of the connection between obesity and cancer. Extensive studies have now been initiated to investigate the mechanisms by which disturbances in sleep duration, sleep continuity and sleep related breathing affect circadian rhythm, central and peripheral tissue oxygenation and metabolism, quality and quantity of dietary intake and circulating inflammatory cytokines and regulatory hormones. This volume aims to present the latest research on sleep, sleep disturbance and its correlation to obesity and cancer.

In vitro utilization of liposomes is now recognized as a powerful tool in many bioscience investigations and their associated clinical studies, e.g., liposomes in drug targeting; liposomes in gene transport across plasma and nuclear membranes; liposomes in enzyme therapy in patients with genetic disorders. However, before these areas can be effectively explored, many basic areas in liposome research require elucidation, including: (a) attachment of liposomes to cell surfaces; (b) permeation of liposomes through the plasma membranes; and (c) stability of liposomes in cell or nuclear matrices. None of these areas have been exhaustively explored and liposome researchers have ample opportunities to contribute to our knowledge. The aim of Liposome Methods and Protocols is to bring together a wide range of detailed laboratory protocols covering different aspects of liposome biology in order to assist researchers in those rapidly advancing medical fields mentioned earlier. With this goal in mind, in each protocol chapter we have detailed the materials to be used, followed by a step-by-step protocol. The Notes section of each protocol is also certain to prove particularly useful, since the authors include troubleshooting tips straight from their benchtops, valuable information that is seldom given in restricted methods sections of standard research journals. For this reason we feel that the book will prove especially useful for all researchers in the liposome field.

The health of the proteome depends upon protein quality control to regulate the proper synthesis, folding, translocation, and clearance of proteins. The cell is challenged constantly by environmental and physiological stress, aging, and the chronic expressions of disease associated misfolded proteins. Substantial evidence supports the hypothesis that the expression of damaged proteins initiates a cascade of molecular events that leads to Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and other diseases of protein conformation.

This is an important and timely volume. The history of research in homocysteine metabolism can be divided into three periods. The first phase was the exploration of the individual reactions and metabolites that characterize the transmethylation and transsulfuration sequences. The former originated with his description of the biosynthesis of methylpyridine and culminated in the work of Cantoni and Axelrod. Similarly the finding that insulin contained cystine was a potent catalyst for the metabolic and nutritional studies of Rose and du Vigneaud. The description and the definition of homocystinuria, a rare inherited meta bolic disorder, marked the beginning of the second historical period. Where previously there had been few laboratories located largely in the United States soon there were numerous research groups representing many nationalities. The more intense focus led to major advances, both in the laboratory and in the clinics. Studies of afflicted individuals, when combined with investigations in experimental animals, provided the basis for a concept of methionine metabo lism that encompassed both transmethylation and transsulfuration. The central role of homocysteine was apparent."

Jurgen Schulte and Christian Endler met in 1990 at an international conference on the Structure of Water held in the Lecture Halls of the University of Graz (Austria). Disappointed by the lack of a systematic strategy of research into the physics of homoeopathy Jurgen Schulte started to work on the establishment of scientifically acceptable research standards in physics of homoeopathy and encouraged academic researchers to establish a coordinated and focused research strategy. In 1994, with the help of major representatives of the international research community, they edited one of the fIrst academic interdisciplinary books on Ultra High Dilution and homoeopathy that underwent a rigorous scientific international referee process before publishing. Due to the dedicated help of the prominent referees (BD Josephson, Nobel Laureate, Cavendish Lab. , Cambridge; M Bastide, Fac de Pharmacy, University Montpellier; RG Jahn, Aerospace Science, Princeton University), the book 1994 was quickly considered a mile stone and turning point for the scientific approach of research into Ultra High Dilution and homoeopathy. Since then the academic research community has grown considerably and many international conferences have been held. Today, research into homoeopathy is to be accepted by the European Union as part of the academic sciences, worthy to be funded at European Union level; an effort that took many years of research coordination and research strategy development. Excerpts of the Research Strategy of the European Committee for Homoeopathy (ECH) have been included in this book.

This book is about Nutraceuticals in cancer therapy, specifically targeted and Adjuvant therapy. It shows several approaches for possibly reducing systemic toxicity. This book illustrates the role of several dietary agents, collectively called nutraceuticals or natural agents in the prevention and/or treatment of human malignancies known to be mediated through alterations in multiple molecular targets. This book contains sixteen chapters which begin with historical perspective on the value of natural agents in the prevention of human malignancies followed by a series of current topics on multiple nutraceuticals targeting multiple cancers. This collection would likely be useful for bringing newer generations with broader perspectives in launching cutting-edge innovative molecular research, which would certainly help in designing targeted clinical trials in order to realize the dream of customize strategies for the prevention and/or treatment of human malignancies without causing any systemic toxicity. Moreover, the knowledge gained would allow novel utilization of nutraceuticals as adjunct to both conventional chemotherapy and radiation therapy in order to improve the overall quality of life and survival of patients diagnosed with cancers.

There has been a dramatic increase in knowledge of tight junctions in the past decade. The molecular structure of tight junctions, cellular functions and the pathophysiological roles of tight junctions are becoming clear. Of the most important functions, the role of the cellular structure in cancer spread and drug delivery are increasingly realised. It is now clear that there are fundamental changes to tight junctions during the process of cancer development. Tight junctions are also critical to the metastatic process of cancer cells. The cellular structure is also crucial in drug therapies, namely, the permeability and bioavailability of the drugs, penetration of barriers such as the blood brain barrier. This current volume aims to summarise the current knowledge of tight junctions, their role in cancer and cancer metastasis and is of interest to scientists and clinicians.

The concept of 'biomineralization' signifies mineralization processes that take place in close association with organic molecules or matrices. The awareness that mineral formation can be guided by organic molecules notably contributed to the understanding of the formation of the inorganic skeletons of living organisms. Modern electron microscopic and spectroscopic analyses have successfully demonstrated the participation of biological systems in several mineralization processes, and prominent examples include the formation of bio-silica in diatoms and sponges. This insight has already made the application of recombinant technology for the production of valuable inorganic polymers, such as bio-silica, possible. This polymer can be formed by silicatein under conditions that cannot be matched by chemical means. Similarly, the efforts described in this book have elucidated that certain organisms, bacteria in deep-sea polymetallic nodules and coccoliths in seamount crusts, are involved in the deposition of marine minerals. Strategies have already been developed to utilize such microorganisms for the biosynthesis and bioleaching of marine deposits. Moreover, studies reveal that bio-polymers enhance the hydroxyapatite formation of bone-forming cells and alter the expression of important regulators of bone resorption, suggesting a potential for bone regeneration and treatment / prevention of osteoporosis.

Laboratory Animal Anaesthesia and Analgesia, Fifth Edition provides a basic guide to anesthesia for a very diverse audience involved in animal testing. This has been the go-to resource for current, clear and evidence-based information for over 30 years. The book is divided into four parts that deal with preparation for anesthesia, including definitions, equipment, preparations, anesthetic and analgesic agents, the management and monitoring of anesthesia, including pre-procedural preparations, monitoring and problems and emergencies through the procedure, advanced and specialized techniques, and analgesia and post-operative care, including recovery and the prevention and management of post-operative pain. Final sections cover anesthesia in common laboratory species, specifically: rodents, rabbits, cats, dogs, ferrets, pigs, sheep and goats, primates, reptiles, amphibians and new specific chapters on birds, fish and cephalopods. This edition keeps up with the tradition of bringing a balanced dose of practical advice, foundational content, and current, updated references, drugs and procedures to veterinarians, technicians, researchers and ethics committee personnel.

Precision Medicine in Neurodegenerative Disorders, Part Two, Volume 193 deals with the "How" in the reconfiguration of our approach to slow the progression of those suffering from diseases of accelerated brain aging. This second Handbook of Clinical Neurology volume offers a rethinking of the animal models on which therapies are tested; outlines the progress and expected changes in biological subtyping efforts using lysosomal, endosomal, mitochondrial, immune dysregulation, and inflammatory mechanisms of disease pathophysiology; and the growing role of microbiome in shaping disease and as a future target of therapeutic efforts. The volume separates the potentially disease-modifying neurorescue and neurorestoration, (e.g., gene therapy and cell replacement therapy) from true precision medicine -matching the biology of those affected with the mechanism of the intervention of interest. Specific chapters are dedicated to the promise and challenges of extracellular vesicles for both diagnosis and treatment, the growing application of digital measures and other evaluations of clinical response, the nuts and bolts of novel adaptive clinical trial designs, and the regulatory changes needed to facilitate drug development for disease-modification purposes.

The increasing importance of sickness and disability data across health-related disciplines is the focus of this concise but comprehensive resource. It reviews the basics of morbidity at the population level by defining core concepts, analyzing why morbidity has overtaken mortality as central to demographic study, and surveying ways these data are generated, accessed, and measured. Subsequent chapters demonstrate how this knowledge can be used to better understand-and potentially solve-critical public health issues, benefitting not only populations served, but also areas such as health services planning, resource allocation, and health policy-setting. To make this material useful to the most readers, this reference: Explains why and how morbidity data are categorized by health professionals and other data users. Examines various methods of identifying and measuring morbidity data. Identifies demographic and non-demographic factors associated with morbidity. Describes and evaluates sources of U.S. morbidity data. Reviews the current state of morbidity in the U.S., and what it means for healthcare and society in general. Suggests future uses of morbidity data in reducing health disparities and improving population health. In Sickness and In Health is uniquely relevant to demographers and demography students, public health professionals, and epidemiologists. Its presentation of concepts and applications makes the book a valuable classroom text and a useful guide for those addressing challenges facing U.S. healthcare.

This, the first of two volumes on personalized medicine in lung cancer, touches on the core issues related to the understanding of lung cancer-statistics and epidemiology of lung cancer-along with the incidence of lung cancer in non-smokers. A major focus of this volume is the state of current therapies against lung cancer-immune, targeted therapies against EGFR TKIs, KRAS, ALK, angiogenesis; the associated challenges, especially resistance mechanisms; and recent progress in targeted drug development based on metal chemistry. Chapters are written by some of the leading experts in the field, who provide a better understanding of lung cancer, the factors that make it lethal, and current research focused on developing personalized treatment plans. With a unique mix of topics, this volume summarizes the current state-of-knowledge on lung cancer and the available therapies.