This volume explores the mechanisms of resistance to targeted therapeutics. The focus is on the cancer cell signaling network, although other mechanisms of resistance including target mutation, and new areas of study such as cancer stem cells are included. Targeted Therapies: Mechanisms of Resistance highlights examples of changes in the signaling network in response to inhibition of a signaling event and underscores the importance in having a mechanistic understanding of the signaling network in cancer for developing effective targeted cancer therapies. Moreover, cutting edge tools to analyze the cell signaling network will be discussed. This includes the leading edge of techniques as well as computational biology and systems theory. This volume provides the reader with both an overview as well as a detailed perspective on the mechanisms of resistance to targeted therapeutics and will be of great value to the oncologist, the physician-scientist treating patients and the translational scientist working on any aspect of targeted therapeutics.

In this book we have taken a comprehensive look at the subject of familial and hereditary gastric tumors. In particular, the aim of this novel editorial work is to propose the correct management of hereditary diffuse gastric cancer patients, focusing in particular on E-cadherin germline mutations, clinical criteria definition, genetic screening and molecular mechanisms, pathology and microscopic features, surgical treatment and clinical approach for asymptomatic mutation carriers. We also describe other inherited predispositions involving gastric carcinoma.

The aim of this book is to return to the biomimicry and medicinal potential that inspired many of the early supramolecular chemists and to set it in the context of current advances in the field.

Following an overview of supramolecular chemistry, the first section considers the efforts made to synthesize artificial systems that mimic biological entities. The second section addresses the application of supramolecular principles to molecular diagnostics with a particular emphasis on the receptor-relayreporter motif. Many of the examples chosen have clinical importance. The third section takes the clinical diagnostic theme further and demonstrates the therapeutic applications of supramolecular chemistry through photodynamic therapy, drug delivery, and the potential for synthetic peptides to form antibiotic tubes. The short epilogue considers the potential for supramolecular solutions to be found for further challenges in biomimetic and therapeutic chemistry.

'I am blown away by the level of detail Phil Cavell brings to his work.' - Elinor Barker MBE, multiple world champion and Olympic gold medallist 'The Midlife Cyclist is a triumph' - Cycling Plus 'An amazing accomplishment... a simple-to-understand precis of your midlife as a cyclist - you won't want to put it down.' - Phil Liggett, TV cycling commentator 'Phil is eminently qualified to write The Midlife Cyclist. Well, he is certainly old enough.' - Fabian Cancellara, Tour de France rider and two-time Olympic champion Renowned cycling biomechanics pioneer, Phil Cavell, explores the growing trend of middle-aged and older cyclists seeking to achieve high-level performance. Using contributions from leading coaches, ex-professionals and pro-team doctors, he produces the ultimate manifesto for mature riders who want to stay healthy, avoid injury - and maximise their achievement levels. Time's arrow traditionally plots an incremental path into declining strength and speed for all of us. But we are different to every other generation of cyclists in human history. An ever-growing number of us are determined to scale the highest peaks of elite physical fitness into middle-age and beyond. Can the emerging medical and scientific research help us achieve the holy triumvirate of speed and health with age? The Midlife Cyclist offers a gold standard road-map for the mature cyclist who aims to train, perform and even race at the highest possible level.

The phenomenon of consciousness has always been a central question for philosophers and scientists. Emerging in the past decade are new approaches to the understanding of consciousness in a scientific light. This book presents a series of essays by leading thinkers giving an account of the current ideas prevalent in the scientific study of consciousness. The value of the book lies in the discussion of this interesting though complex subject from different points of view ranging from physics and computer science to the cognitive sciences. Reviews of controversial ideas related to the philosophy of mind from western and eastern sources including classical Indian first person methodologies provide a breadth of coverage that has seldom been attempted in a book before. Additionally, chapters relating to the new approaches in computational modeling of higher order cognitive function and consciousness are included. The book is of great value for established as well as young researchers from a wide cross-section of interdisciplinary scientific backgrounds, aiming to pursue research in this field, as well as an informed public.
* Presents the latest developments in the scientific study of consciousness
* Critically reviews different theoretical and philosophical explanations related to the subject
* An important book for both students and researchers in designing research projects on consciousness

Amyloid-forming proteins are implicated in over 30 human diseases. The proteins involved in each disease have unrelated sequences and dissimilar native structures, but they all undergo conformational alterations to form fibrillar polymers. The fibrillar assemblies accumulate progressively into disease-specific lesions in vivo. Substantial evidence suggests these lesions are the end state of aberrant protein folding whereas the actual disease-causing culprits likely are soluble, non-fibrillar assemblies preceding the aggregates. The non-fibrillar protein assemblies range from small, low-order oligomers to spherical, annular, and protofibrillar species. Oligomeric species are believed to mediate various pathogenic mechanisms that lead to cellular dysfunction, cytotoxicity, and cell loss, eventuating in disease-specific degeneration and systemic morbidity. The particular pathologies thus are determined by the afflicted cell types, organs, systems, and the proteins involved. Evidence suggests that the oligomeric species may share structural features and possibly common mechanisms of action. In many cases, the structure function interrelationships amongst the various protein assemblies described in vitro are still elusive. Deciphering these intricate structure function correlations will help understanding a complex array of pathogenic mechanisms, some of which may be common across different diseases albeit affecting different cell types and systems."

The atlas of the Light and Specular Microscopy of the Cornea, particularly of the corneal endothelium presents photographs of healthy and pathological corneas, as well as corneas prepared for grafting. Photographs are taken from donor or patient's corneas. The first part section of the atlas shows healthy corneas and its particular layers: the epithelium (superficial and basal cells, subepithelial nerve plexus), stroma and keratocytes, and the endothelium. Blood vessels or palisades of Vogt in limbus are shown as well. The second part section that shows corneas processed for grafting is focused focuses on the endothelial layer. Main causes of exclusion of corneas from grafting, such as the presence of dead cells, polymeghatism, pleomorphism, cornea guttata or stromal scars have been shown. The third part section of the atlas shows corneas before and after storage in tissue cultures or hypothermic conditions with the aim to assess its suitability of for tissue for grafting. The last final section contains photographs of pathological corneal explants

This volume provides an overview of the cytoskeleton particularly on the fundamental role the cytoskeleton plays in the regulation of cell structure and function. This book represents new trends in cytoskeletal research that go beyond the traditional approach of identifying new proteins in the cytoskeleton, but actually define how these proteins interact with signaling pathways. While the major emphasis in this volume remains on the microfilament structure, some discussion has been included in this volume to illustrate the similarities and differences between the three cytoskeletal elements namely the actin microfilament, the intermediate filaments and the microtubules.

This book provides an overview of modern sensing technologies and reflects the remarkable advances that have been made in the field of intelligent and smart sensors, environmental monitoring, health monitoring, and many other sensing and monitoring contexts in today's world. It addresses a broad range of aspects, from human health monitoring to the monitoring of environmental conditions, from wireless sensor networks and the Internet of Things to structural health monitoring. Given its breadth of scope, the book will benefit researchers, practitioners, technologists and graduate students involved in the monitoring of systems within the human body, functions and activities, healthcare technologies and services, the environment, etc.

Case-based reasoning (CBR) is an Artificial Intelligence (AI) technique to support the capability of reasoning and learning in advanced decision support systems. CBR exploits the specific knowledge collected on previously encountered and solved situations, which are known as cases. In this book, we have collected a selection of papers on very recent CBR applications. These, after an in-depth analysis of their specific application domain needs, propose proper methodological solutions and give encouraging evaluation results, which have in some cases led to the commercialization step. The collected contributions demonstrate the capability of CBR to solve or handle issues which would be too difficult to manage with other classical AI methods and techniques, such as rules or models. The heterogeneity of the involved application domains indicates the flexibility of CBR, and its applicability in all those fields where experiential knowledge is (readily) available.

This is the second of three planned volumes in the Methods in Enzymology series on the topic of stem cells. This volume is a unique anthology of stem cell techniques focusing on adult stem cells, and written by experts from the top laboratories in the world. The contributors not only have hands-on experience in the field but often have developed the original approaches that they share with great attention to detail. The chapters provide a brief review of each field followed by a "cookbook" and handy illustrations. The collection of protocols includes the isolation and maintenance of stem cells from various species using "conventional" and novel methods, such as derivation of ES cells from single blastomeres, differentiation of stem cells into specific tissue types, isolation and maintenance of somatic stem cells, stem cell-specific techniques and approaches to tissue engineering using stem cell derivatives. The reader will find that some of the topics are covered by more than one group of authors and complement each other. Comprehensive step-by-step protocols and informative illustrations can be easily followed by even the least experienced researchers in the field, and allow the setup and troubleshooting of these state-of-the-art technologies in other laboratories.
* Provides complete coverage spanning from derivation/isolation of stem cells, and including differentiation protocols, characterization and maintenance of derivatives and tissue engineering
* Presents the latest most innovative technologies
* Addresses therapeutic relevance including FDA compliance and tissue engineering

SocialBonding,aProductofEvolution: anIntroductiontotheVolume Mechanisms underlying reproductive and maternal functions or coping represent the initialstructuringforcebehindmanysocialbehaviors.Theyareaccompaniedbysel- tivehormonalenvironmentsaimedatfacilitatingor stabilizingthem.Sexandadrenal steroids are major players in the regulation of reproductive functions and coping challenges, but other hormones also participate in a variety of social behaviors (in particular,oxytocinandvasopressin,twophylogeneticallyveryoldmoietiesoriginally associated with maternal care and water balance) and are receiving increasing att- tion. Their role is highlighted in the present volume, which gathers contributions to theColloqueMedicineetRecherche"HormonesandSocialBehavior"organizedbythe FondationIPSENinDecember 2007. Whatisthekeytounderstandingtherationaleofhormonalsubstratesofbehavior? Evolution, of course. Higher manifestations of social behavior have evolved from - productivebehavior,characterizedbyErnstMayras"theleadingedgeofevolutionary change." As formulated by one contributor to thisvolume, however, "the evolutionary increase in neocortex seen in primates has induced a signi?cant emancipation of - havior from hormonal determinants, and in parallel, an increasing role for intelligent socialstrategies"(Keverne 2008). In so-called "lower" mammalian animals, many social behaviors are closely - pendent upon the olfactory system, a component of autonomous regulation of such importancethatitexpressesalargeproportionofallreceptorgenespresentinthebrain. Whenonelooksat"higher"mammalssuchasprimates,olfactorycontrolbecomesless stringent. Olfactory structures exhibit the same number of receptor genes, but a large number are transformed into non-coding "pseudogenes." In parallel, hormones i- tially targeted on physiological functions become increasingly associated with more diversi?edcognitivefunctions.

Psychoneuroimmunology (PNI) has developed rapidly in the last four decades. As a multidisciplinary area, PNI may provide a scientific basis for mind-body relationships toward the development of personalized and systems medicine. In Psychoneuroimmunology:Methods and Protocols, expert researchers in the field detail methods and protocols geared toward the development of integrative and individualized therapeutics in multiple dimensions from drugs to behaviors. Written in the highly successful Methods in Molecular Biology (TM) series format, the chapters include the kind of detailed description and implementation advice that is crucial for getting optimal results in the laboratory. Thorough and intuitive, Psychoneuroimmunology:Methods and Protocols aids scientists in continuing to study holistic views for the translation of psychoneuroimmunology into better preventive and personalized medical practice.

This book is a collection of articles presented by researchers and practitioners, including engineers, biologists, health professionals and informatics/computer scientists, interested in both theoretical advances and applications of information systems, artificial intelligence, signal processing, electronics and other engineering tools in areas related to biology and medicine in the All India Seminar on Biomedical Engineering 2012 (AISOBE 2012), organized by The Institution of Engineers (India), Jabalpur Local Centre, Jabalpur, India during November 3-4, 2012. The content of the book is useful to doctors, engineers, researchers and academicians as well as industry professionals.

Over the past 10 years, work on acute promyelocytic leukemia (APL) has become the paradigm of translational research that began with the discovery of a recurrent chromosomal translocation, followed by the identification of the genes and proteins involved, finding their molecular functions in transcriptional control, establishing mouse models and culminating in the development of targeted therapy.

This cutting-edge book explores recent progress in the microelectronics arena. It examines the resultant miniaturization of component device features to nanometer size particles, and the ensuing growth in the development and use of microchip-based techniques in leading laboratories around the world. In the sixteen chapters of this volume, leading scientists present technically precise microchip-based assays for a variety of applications.

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.

History, Wild Mice, and Genetics, the first volume in the four volume set, The Mouse in Biomedical Research, provides information about the history, biology and genomics of the laboratory mouse (Mus musculus), as well as basic information on maintenance and use of mouse stocks. Mouse origins and relationships are covered in chapters on history, evolutionary taxonomy and wild mice. Genetics and genomics of the mouse are covered in chapters on genetic nomenclature, gene mapping, cytogenetics and the molecular organization of the mouse genome. Maintenance of laboratory mice is described in chapters on breeding systems for various types of strains and stocks and genetic monitoring. Use of the mouse as a model system for basic biomedical research is described in chapters on chemical mutagenesis, gene trapping, pharmacogenetics and embryo manipulation. The information in Volume 1 serves as a primer for scientists new to the field of mouse research.

With data from the United States and Europe, Jon Miller and Linda Kimmel examine the public's understanding of and attitude toward biotechnology and biomedicine while they present methods of introducing cutting edge science to the
nonscientist. Biomedical Communications illustrates how vital it is for researchers, journalists, and policy makers to clearly communicate their findings in a way that avoids general misconception or confusion. The authors explore how to acquire information about biomedical policy, discuss strategies for informing consumers, and present tactics for improving biomedical communication with the public.
TOPICS COVERED:
* Using Research to Improve Biomedical Communications
* The Public Understanding of Biomedical Science
* Strategies for Communications to Consumers
* Public Attitudes Toward Biotechnology Issues

This book summarizes the main surface analysis techniques that are being used to study biological specimens/systems. The compilation of chapters in this book highlight the benefits that surface analysis provides.

The outer layer of bulk solid or liquid samples is referred to as the surface of the sample/material. At the surface, the composition, microstructure, phase, chemical bonding, electronic states, and/or texture is often different than that of the bulk material. The outer surface is where many material interactions/reactions take place. This is especially true biomaterials which may be fabricated into bio-devices and in turn implanted into tissues and organs. Surfaces of biomaterials (synthetic or modified natural materials) are of critical importance since the surface is typically the only part of the biomaterial/bio-device that comes in contact with the biological system.

Analytical techniques are required to characterize the surface of biomaterials and quantify their impact in real-world biological systems. Surface analysis of biological materials started in the 1960 s and the number of researchers working in this area have increased very rapidly since then, a number of advances have been made to standard surface analytical instrumentation, and a number of new instruments have been introduced.

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Presenting topics from the basic application of molecular genetics to more complex gene expression analysis using different models of study, this detailed volume explores asthma through the lens of genetics, considered to play an essential role in the etiopathogenesis of the disease. Since asthma is a complex disease, this book is designed to provide a review of the most useful techniques with examples of their applications in specific laboratory protocols. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and practical, Molecular Genetics of Asthma serves as an ideal guide to researchers investigating this vital field of study.

The Advances in Cancer Research series provides invaluable information on the exciting and fast-moving field of cancer research. This volume stands as the first ever thematic volume in the series, focusing on the topic of genomics in cancer drug development. The chapters included in this book represent the cutting-edge information in the field and span such topics as Mass Spectrometry: Uncovering the Cancer Proteome for Diagnostics; Biomarker Discovery in Epithelial Ovarian Cancer by Genomic Approaches; The Application of siRNA Technology to Cancer Biology Discovery; Ribozyme Technology for Cancer Gene Target Identification and Validation; Cancer Cell-Based Genomic and Small Molecule Screens; Tumour Antigens as Surrogate Markers and Targets for Therapy and Vaccines; Practices and Pitfalls of Mouse Cancer Models in Drug Discovery; Biomarker Assay Translation from Discovery to Clinical Studies in Cancer Drug Development - Quantification of Emerging Protein Biomarkers; Molecular Optical Imaging of Therapeutic Targets of Cancer; Cancer Drug Approval in the United States, Europe and Japan.

This second edition expands upon the previous volume with additional emphasis on recent innovation in basic renal research and has a more holistic approach on associated disorders such as complications associated with peritoneal dialysis, ischemic acute kidney injury, the sympathetic nervous system, and vascular calcification. The book is divided into five parts: Part I provides a number of in vitro, in vivo, and ex vivo models of kidney disease and associated complications; Part II looks at recent advances in imaging techniques; Part III covers recent developments in studying metabolism in renal ischemia and reperfusion; Part IV addresses study and measurement of vascular calcification; and Part V explores analytical techniques that are both topical and of widespread relevance to the study of experimental renal disease. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Kidney Research: Experimental Protocols, Second Edition is a valuable collection of protocols useful to new and experienced researchers who are interested in the field of Nephrology.

Normative Biology, Husbandry, and Models, the third volume in the four volume set, The Mouse in Biomedical Research, encompasses 23 chapters whose contents provide a broad overview on the laboratory mouse's normative biology, husbandry, and its use as a model in biomedical research. This consists of chapters on behavior, physiology, reproductive physiology, anatomy, endocrinology, hematology, and clinical chemistry. Other chapters cover management, as well as nutrition, gnotobiotics and disease surveillance. There are also individual chapters describing the mouse as a model for the study of aging, eye research, neurodegenerative diseases, convulsive disorders, diabetes, and cardiovascular and skin diseases. Chapters on imaging techniques and the use of the mouse in assays of biological products are also included.