Presents the latest developments on the interaction of metal complexes with nucleic acids, the building blocks of life. Bioinorganic chemistry is a highly interdisciplinary area of research and is of great interest to scientists working in the fields of coordination chemistry, biochemistry, supramolecular chemistry, nanotechnology, computational chemistry, and inorganic chemistry in general. Includes the latest research in DNA recognition by supramolecular metal complexes. Describes the applications of this exciting area of research in metal-nucleic acid chemistry.

Legal in 23 states as of June 2014, medicinal Cannabis sativa is widely used, with mainstream news and scientific sources reporting success stories of people suffering from such diverse medical conditions as epilepsy, cancer and chronic pain. In states where it remains illegal, however, providers of medicinal cannabis risk arrest. While the United States government restricts medicinal cannabis research, advances have been made in Israel, Spain and Italy. One such breakthrough was the discovery of cannabinoids (compounds found in cannabis) that mimic endogenous neurotransmitters in the brain and in the immune system, and are thus likely to be able to directly affect a host of degenerative diseases. Focusing on the biochemical properties, medical benefits and psychological effects of cannabinoids, this book provides an overview of current research and clinical trials, examines the rationales behind cannabis' status as a Schedule I narcotic and discusses the uses of industrial hemp.

The new age of biologic treatment of the ACL is coming. In The ACL Handbook: Knee Biology, Mechanics, and Treatment, the authors cover the past and current state of ACL injuries and treatment, and then introduce and explain the key concepts for understanding the new biologic approach to ACL treatment. The use of factors to enhance graft healing are reviewed, as well as an in-depth review of the science of platelet-rich plasma and its cellular components (platelets, white cells, and plasma). Chapters on in vitro models for science as well as the advantages and disadvantages of animal models for ACL research are included, as are chapters on the new technique of bio-enhanced ACL repair. All are discussed in easily readable text aimed at anyone with an interest of what is coming next in ACL surgery.

Researching, Reflecting and Writing about Work provides a guide to the research skills and critical thinking required to complete a research project for professional learning courses in counselling and psychotherapy.

Written at a level easily accessible to those enrolled on a work-based qualification as well as those considering postgraduate research at master's level, this book includes:

• how we reflect on our work
• discussion on preparation and structuring of a case study
• how to present work in supervision with advice on process recording
• essay plan structures and appropriate methodologies for research
• ethical considerations and critical linking
• dilemmas and tensions involved in 'research at work'.

Key learning points and reflective exercises are included throughout and theory is supported by contributions detailing specific learning experiences from a variety of work settings, including the public sector, an organisation, in the community, and as an independent counsellor in a voluntary agency. There is also a section on how to prepare your research for consideration for publication and how to present your findings to colleagues.

Researching, Reflecting and Writing about Work will be of interest to all those on counselling courses, or training as psychotherapists, as well as people involved in professional learning linked to the helping professions, including those interested in work-based research linked to therapy in any setting.

This book is an updated reference for one of the most exciting field of biomedical researches- Stem Cell Research and its therapeutic applications. Stem cell research holds great promise for the treatment of many human diseases that currently lack effective therapies. The set of chapters in this book provide insights into both basic stem cell biology and clinical applications of stem cell-based cell replacement therapies for a variety of human diseases, including cardiovascular diseases, neurological disorders, and li ver degeneration. It also covers novel technologies for the culture and differentiation of both human embryonic stem cells and adult tissue stem cells. This book summarizes our current state of knowledge in stem cell research and integrates basic stem cell biology with regenerative medicine in an overall context. It is an essential reference for students, postdoctoral fellows, academic and industrial scientists, and clinicians. v Acknowledgements The editors would like to thank Ms. Jill Brantley, Rose Chavarin, Alina Haas, and Emily Sun for their administrative assistance and proof-reading of this book. We would also like to thank all the authors for their contributions. vii The editors wish to dedicate this book to our mentors Ron Evans, Fred Gage, and, in memory of Daniel E. Koshland, Jr. Contents Preface . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . v Acknowledgements . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Contributors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . xi 1 Retinal Pigment Epithelial Cells: Development In Vivo and Derivation from Human Embryonic Stem Cells In Vitro for Treatment of Age-Related Macular Degeneration . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Dennis O. Clegg, David Buchholz, Sherry Hikita, Teisha Rowland, Qirui Hu, and Lincoln V.

A Practical Guide to Managing Clinical Trials is a basic, comprehensive guide to conducting clinical trials. Designed for individuals working in research site operations, this user-friendly reference guides the reader through each step of the clinical trial process from site selection, to site set-up, subject recruitment, study visits, and to study close-out. Topics include staff roles/responsibilities/training, budget and contract review and management, subject study visits, data and document management, event reporting, research ethics, audits and inspections, consent processes, IRB, FDA regulations, and good clinical practices. Each chapter concludes with a review of key points and knowledge application. Unique to this book is "A View from India," a chapter-by-chapter comparison of clinical trial practices in India versus the U.S. Throughout the book and in Chapter 10, readers will glimpse some of the challenges and opportunities in the emerging and growing market of Indian clinical trials.

The objective of this CTMI volume is to provide readers with a foundation for understanding what ADARs are and how they act to affect gene expression and function. Because A-to-I editing may affect base-pairing and RNA structure, processes including translation, splicing, RNA replication, and miR and siRNA silencing may be affected. It also is becoming increasingly apparent that ADARs may possess roles not only as enzymes that deaminate adenosine to produce inosine in RNA substrates with double-stranded character, but also as proteins independent of their catalytic property. Future studies of ADARs no doubt will provide us with additional surprises and new insights into the modulation of biological processes by the ADAR family of proteins.

Thin layer chromatography (TLC) is well suited for performing enantioseparations for research as well as larger-scale applications. A fast, inexpensive, and versatile separation technique, there are many practical considerations that contribute to its effectiveness. Thin Layer Chromatography in Chiral Separations and Analysis is the first book to focus solely on the theory, capabilities, and applications of TLC for direct and indirect enantioseparations. The first part of the book examines the fundamental principles of chirality and TLC. It describes the necessary materials, laboratory equipment, procedures, and strategies for the separation, quantification, isolation, and analysis of chiral compounds. The second part evaluates the real-world enantioseparations and densitometric analyses. Emphasizing pharmaceutical applications, the book discusses chiral separation mechanisms and methods for analyzing the chiral purity of diastereoisomers, amino acids, beta-blockers, and NSAIDS. Topics also include commercial stationary phases and chiral modifiers of mobile phases. Thin Layer Chromatography in Chiral Separations and Analysis presents a unified perspective of theory and experimental details underlying the collective developments in the field. The book offers scientists in a variety of disciplines and levels of expertise a complete guide to understanding the current and potential applications of chiral TLC.

Since the last major compendium dedicated to cyclic nucleotide phosphodiesterases (PDEs) was published over 15 years ago, an enormous amount of progress has occurred in the field. There is great need for a centralized source for key information in this burgeoning and therapeutically important area of medical research. Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an integrated volume covering PDE biology from genes to organisms. It examines phosphodiesterases as pharmacological targets as well as the development of specific PDE inhibitors as therapeutic agents. With contributions from pioneers in the field, individual chapters describe one of the 11 known mammalian PDE families including the molecular characteristics, structure, function, and traits unique to each. Characteristics of PDEs from lower organisms are also the subject of other chapters since they provide key insights into PDE functions and are also pharmacological targets for treatment of a variety of diseases in humans and domestic animals. Chapters on the current biomedical and therapeutic research on PDEs include studies on gene-targeted knockout strategies and compartmentation in cyclic nucleotide signaling. By unraveling the unique cellular roles for different PDEs, scientists are beginning to open the door to the therapeutic use of PDE inhibitors for the treatment of a number of pathological conditions including asthma and inflammation, pulmonary hypertension, erectile dysfunction, and stroke. By collating current information into a coherent and coordinated perspective, Cyclic Nucleotide Phosphodiesterases in Health and Disease provides an invaluable reference for industry and clinical scientists and points toward future directions of research and therapeutic advancements in developing selective inhibitors for these various enzymes.

Monoclonal antibodies have had their impact on biomedical research for more than a decade. Beside their exuberant use as reagents, quite a number of diagnostic and therapeutic approaches have been followed and an impressive number of technological improvements, e.g., humanization, recombinant miniantibodies, have been elaborated to strengthen the principle. With respect to clinical applications, the first generation of antibody 'drugs' is yielding promising results while second and third generation antibody constructs are already underway. The book reviews the status of technological development and brings this into the perspective of clinical results. A rapidly growing amount of clinical data is collected in an expanding number of indications. Hence, the review of clinical study results has been grouped according to the fields of oncology and of chronic and acute inflammation. This book will be of interest to scientists working in the fields of oncology, immunology, internal medicine and clinical chemistry.

The EuroQol Group first met in Rotterdam in May 1987 determined to develop a standardised non-disease-specific instrument for valuing health-related quality of life. The book traces the activities of the Group over the next 25 years. The instrument constructed, eventually named the EQ-5D, was translated into many languages and used in a wide range of countries and settings. The book describes how the instrument's descriptive system was determined, how translation and language issues were handled, and how valuations were provided. Recent developments, in particular a 5-level version (EQ-5D-5L), and a youth version (EQ-5D-Y) are covered. The history of the institutional and administrative framework within which the Group operated is also treated.

Gives a convenient summary of trials in Gynecologic Oncology Supplies an invaluable revision primer for those undertaking certification Provides a uniquely up-to-date resource

This volume describes important medical discoveries, from the introduction of the first antibiotic to the present, where serendipity, intuition, coincidence, or laboratory accident played an important role in bringing a discovery to light. Although chance is the principal determinant, the book emphasizes other factors, such as economic and political exigencies and being in the right place at the right time.

It is estimated that 80 to 90% of drugs under development never make it to the marketplace due to insufficient clinical activity, unacceptable toxicity, rapid appearance of drug resistance, or other factors that should be, at least partially, predictable from preclinical testing. This new text asks the question, "How can we use computational methods to improve the success rate in drug development?" Computer Techniques in Preclinical and Clinical Drug Development shows how modeling makes it possible to extract the maximum amount of information and predictive value from preclinical data. Computer modeling methods from the areas of pharmacokinetics, pharmacodynamics, cytokinetics, and inhibition kinetics of multi-enzyme pathways are all discussed in this unique reference source.

A comprehensive guide for physicians conducting clinical research, this second edition addresses a broader research perspective. It includes information on the implications of the ICH Guidelines, current FDA regulations, and an Internet address directory. Everything the clinical trial manager, planner, monitor, and investigator need to know about the design, establishment, monitoring, and close-out of a trial is in this book. The chapters address the elements of clinical research, professional interactions, FDA regulations and good clinical practices guidelines, investigational agent management, designing a study and protocol development, conducting the study, and more.

This open access book is the first published guide about how to analyse data produced by the EQ-5D, one of the most widely used Patient Reported Outcomes questionnaires world wide. The authors provide practical, clear and comprehensive guidance in five concise chapters. Following an overview of the EQ-5D and its analysis, we describe how the questionnaire data - the EQ-5D profile and EQ VAS - can be analysed in different ways to generate important insights into peoples' health. We then show how the value sets which accompany the EQ-5D can be applied to summarise patients' data. The final chapter deals with advanced topics, including the use of Minimally Important Differences, case-mix adjustment, mapping, and more. This book is essential for those new to analyzing EQ-5D data and will be also be valuable for those with more experience. The methods can be applied to any EQ-5D instrument (for example, the three- and five-level and Youth versions) and many of the methods described will be equally relevant to other Patient Reported Outcomes instruments.

Taking readers from the research laboratory to the bedside, this Second Edition compiles essential information on the pharmacodynamics of all major classes of the antimicrobial armamentarium including penicillins, cephalosposorins, cephamycins, carbapenems, monobactams, aminoglycosides, quinolones, macrolides, antifungals, antivirals, and emerging agents currently in development. Written by experienced professionals in the field, this guide uses an abundance of examples to depict methods to apply pharmacodynamic concepts to everyday clinical practice.

This book reviews the history, regulatory status, pharmacopeial specifications, and harmonization of pharmaceutical excipients in the United States and Europe, and provides a comprehensive understanding of the current scientific basis for safety evaluation and risk assessment. Examines excipients as a unique class of products and explores new procedures for determining toxicity! A timely and unique addition to the pharmaceutical literature, containing over 570 citations that support and enhance the text, Excipient Toxicity and Safety identifies the differences between excipients (inactive ingredients), food ingredients, and drug products evaluates issues of dose administration, species selection, and study design for various routes of exposure provides detailed information on the historical uses of excipients in drug formulations clarifies the Safety Committee of the International Pharmaceutical Excipients Council's (IPEC) guidelines and technical specifications for conducting tests for each route of exposure explains how data generated in toxicity models are applied to identify hazards in drug formulations details exposure assessment to link hazard identification with risk considers the requirements and importance of purity specifications and much more! Excipient Toxicity and Safety is a blue-ribbon reference ideal for pharmacists; toxicologists; pharmacologists; analytical chemists; quality control, quality assurance, and regulatory compliance managers; and upper-level undergraduate and graduate students in these disciplines.

Increase in antibiotic resistance has forced researchers to develop new drugs against microorganisms. Lipopeptides are produced as secondary metabolites by some microorganisms. Computer-aided Design of Antimicrobial Lipopeptides as Prospective Drug Candidates provides the identification of novel ligands for different antimicrobial lipopeptides. Along with identification, it also provides some of the in silico drug design processes, namely homology modelling, molecular docking, QSAR studies, drug ADMET studies and pharmacophore studies to check the ligand-lipopeptide interaction. Some lipopeptides have shown anti-cancerous properties too, and this book discusses the required templates to design new drugs using computational techniques. Key Features: Focuses on the use lipopeptides as new antimicrobial compounds Presents the basics of in silico modelling for design and development of new drug molecules, and is therefore of interest to beginners in the field Provides a step-by-step process for identification of drug molecules and testing its efficacy in silico Couples with courses on patents and intellectual property rights

Sponsor companies and CROs alike will appreciate the industry-wide analysis, practical, how-to advice, and helpful charts and checklists provided by Outsourcing in Clinical Drug Development. A panel of experts discuss supplier identification and selection, financial considerations, and the ethical issues. They cover contracting out laboratory analysis, data management, and statistical services, and the effects of outsourcing on quality assurance. Whether readers are beginning to explore the possibility of outsourcing or already involved in long-term strategic outsourcing partnerships, this invaluable resource is a complete guide to the drug development outsourcing relationship.

It is pointed out that a cancer stem cell is a type within a tumor that possesses the capacity of self-renewal and can give rise to the heterogeneous lineages of cancer cells, which comprise the tumor. It is emphasized that a unique feature of cancer stem cells is that, although conventional chemotherapy kills most cells in a tumor, cancer stem cells remain intact. Vast applications of the following specific stem cells in disease and tissue injury are discussed: embryonic stem cells, human mesenchymal stem cells, cancer stem cells, arterial stem cells, neural stem cells, cardiac stem cells, dental stem cells, limbal stem cells, and hematopoietic stem cells. Because human embryonic stem cells possess the potential to produce unlimited quantities of any human cell type, considerable focus is placed on their therapeutic potential in this volume. These cells are used in tissue engineering, regenerative medicine, pharmacological and toxicological studies, and fundamental studies of cell differentiation. It is pointed out that the formation of embryoid bodies, which are three-dimensional aggregates of embryonic cells, is the initial step in the differentiation of these cells. Therapeutic implications of signalling pathways in cancer stem cells are pointed out. Targeting self-renewal pathways in cancer stem cells are also included. Application of mesenchymal stem cells for treating ischemic brain injury is explained. Neural stem cells proliferation into the surrounding area of the traumatic brain injury is explained.

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Once the existence of free radicals was proven, an avalanche of studies on free radical-mediated biological processes ensued. The study of reactive oxygen and nitrogen species (ROS and RNS) is center stage in biological free radical investigations. Written by a biochemist, Signaling Mechanisms of Oxygen and Nitrogen Free Radicals discusses the regulatory functions of ROS and RNS in physiological and pathophysiological states. An exploration of the main questions of signaling mechanisms of reactive oxygen and nitrogen species in enzymatic processes, this book draws attention to the chemical mechanisms of these reactions. It elucidates the differences between signaling functions and damaging effects of ROS and RNS in biological systems. The text also covers free radical signaling processes catalyzed by enzymes, producers of superoxide and nitric oxide that are able to use produced ROS and RNS as signaling species in their own catalytic processes. It then examines ROS and RNS signaling produced by mitochondrial enzymes. The author explores signaling functions of ROS and RNS in enzymatic heterolytic reactions, supplying important data on ROS and RNS signaling in the catalysis by the enzymes which do not produce free radicals by themselves. He provides information on signaling by reactive oxygen and nitrogen species in apoptosis and aging/senescence and concludes with coverage of mechanisms of free radical signaling in enzymatic processes. The book provides new understanding of signaling functions in living organisms related to cardiovascular processes, cancer, inflammation, hereditary diseases, and their regulation of physiological functions such as development, aging, and senescence. This information can support the development of new drugs and novel treatment methods.

Emphasizing the role of good statistical practices (GSP) in drug research and formulation, this book outlines important statistics applications for each stage of pharmaceutical development to ensure the valid design, analysis, and assessment of drug products under investigation and establish the safety and efficacy of pharmaceutical compounds. Coverage include statistical techniques for assay validation and evaluation of drug performance characteristics, testing population/individual bioequivalence and in vitro bioequivalence according to the most recent FDA guidelines, basic considerations for the design and analysis of therapeutic equivalence and noninferiority trials.

Landmark Papers in Cardiovascular Medicine provides a thorough and wide-ranging analysis of core examples of novel research, clinical trials and seminal papers published in the medical literature that have paved the way for breakthroughs in the management of the entire spectrum of cardiovascular disease. These papers may have produced positive, negative or equivocal findings but are regarded by the experts as having either stimulated a paradigm shift in therapeutic strategy or been the catalyst for new and improved methods of research, diagnosis or drug development. Our aim is to provide both a benchmark and inspiration for future work in the field of cardiovascular medicine and also to give the reader an insight into the mechanics and infrastructure of how high-quality evidence-based medicine has been produced. Each trial summary is punctuated by sections on 'strengths and limitations', 'impact on the field', 'learning points' and 'further reading' suggestions that allow for a completely holistic analysis of the data. The experts also give their views on what research is currently underway, their hopes for the future and what advances they predict will occur in each subspecialty field of cardiovascular medicine, making this book essential reading for all those individuals with an interest in the field.

NMR spectroscopy has undergone a revolution in recent years with the advent of several new methods overcoming the problems of sensitivity and resolution. Recent developments in biotechnology have made it easier and economical to introduce 13C, 15N and 2H into proteins and nucleic acids. At the same time, there has been an explosion in the number of NMR experiments that utilize such isotope labeled samples. Thus, a combination of isotopic labeling and multidimensional, multinuclear NMR has opened up new avenues for structural studies of proteins, nucleic acids and their complexes.

This book will focus on recent developments in isotope labeling methods for structural studies of small molecules, peptides, proteins and nucleic acids. The aim of the book is to serve as a compendium of isotope labeling for the biomolecular NMR community providing comprehensive coverage of the existing methods and latest developments along with protocols and practical hints on the various experimental aspects. The book will cover a wide range of topics in isotope labeling under one title including emerging areas of metabolonomics and solid state NMR.