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Comedy horror starring Trevor Matthews as Jack Brooks, a man who is left consumed by rage after witnessing the brutal murder of his family when he was a child. Years later, Jack is a plumber whose life has been on a continuous downward spiral since that fateful day. One day, while Jack is attempting to repair some pipes for Professor Crowley (Robert Englund), he unwittingly awakens an ancient evil which possesses the Professor's soul. The Professor's body begins to slowly transform and Jack must now harness his anger for the powers of good and face the forces of evil that killed his family.
Get ready for the ultimate adventure! All 21 original Tintin animated adventures are collected here over 5 discs and with 840 minutes of the original animation. This is your chance to relive (or introduce the family to) the original adventurer!
Tintin is the world's most famous boy reporter. With his faithful dog Snowy at his side, the intrepid pair travel the globe to investigate exciting cases. Along the way they encounter a colourful cast of characters who have become familiar to generations of children and adults, including the boisterous Captain Haddock, accident prone Thompson and Thomson and the absent-minded Professor Calculus.
Whether you grew up with these classic adventures or are a newcomer,The Adventures of Tintin will make the perfect family-friendly viewing!
During the 1920s and 1930s thousands of European and American writers, professionals, scientists, artists, and intellectuals made a pilgrimage to experience the "Soviet experiment" for themselves. Showcasing the Great Experiment explores the reception of these intellectuals and fellow-travelers and their cross-cultural and trans-ideological encounters in order to analyze Soviet attitudes towards the West. Many of the twentieth century's greatest writers and thinkers, including Theodore Dreiser, Andre Gide, Paul Robeson, and George Bernard Shaw, notoriously defended Stalin's USSR despite the unprecedented violence of its prewar decade. While many visitors were profoundly affected by their Soviet tours, so too was the Soviet system. The early experiences of building showcases and teaching outsiders to perceive the future-in-the-making constitute a neglected international part of the emergence of Stalinism at home. Michael David-Fox contends that each side critically examined the other, negotiating feelings of inferiority and superiority, admiration and enmity, emulation and rejection. By the time of the Great Purges, these tensions gave way to the dramatic triumph of xenophobia and isolationism; whereas in the twenties the new regime assumed it had much to learn from Western modernity, by the Stalinist thirties the Soviet order was declared superior in all respects. Drawing on the declassified archival records of the agencies charged with crafting the international image of communism, David-Fox shows how Soviet efforts to sell the Bolshevik experiment abroad through cultural diplomacy shaped and were, in turn, shaped by the ongoing project of defining the Soviet Union from within. These interwar Soviet methods of mobilizing the intelligentsia for the international ideological contest, he argues, directly paved the way for the cultural Cold War.
Traditional Chinese medicine has a strong scientific basis, but the science of these important preparations is often rarely discussed. Western approaches often simplify traditional Chinese medicine to drug discovery in Chinese plants, however, the majority of traditional Chinese medications use complex mixtures of plant extracts, rather than single purified drugs. The combination of different extracts is based on yin, yang and chi theories, which are often poorly understood in the West. Yin and yang are known to be the balance of agonists and antagonists, whereas chi derives from signalling processes in the body and regulates bodily functions. Traditional Chinese medical practitioners understand that yin, yang and chi constantly interact in the body to maintain health. Western medical practitioners understand how to use agonists and antagonists and how to modify signalling processes, but generally do not accept the use of complex plant extracts to perform these functions. Aimed at medical scientists, and including detailed explanations of the theories behind the science, this text may help researchers to understand Chinese medical practitioners and to communicate more effectively with them. It will also lead to greater acceptance of traditional medications in the West. Presenting a clear rationale for the use of traditional Chinese medications in Western medical facilities, it enables scientists to find new directions in experimental design and encourage examination of these useful, but often poorly understood, preparations in clinical trials.
This book examines how cryptocurrencies based on blockchain technologies fit into existing general law categories of public and private law. The book takes the common law systems of the United Kingdom as the centre of its study but extends beyond the UK to show how cryptocurrencies would be accommodated in some Western European and East Asian legal systems outside the common law tradition. By investigating traditional conceptions of money in public law and private law the work examines the difficulties of fitting cryptocurrencies within those approaches and models. Fundamental questions regarding issues of ownership, transfer, conflict of laws, and taxation are addressed with a view to equipping the reader with the tools to answer common transactional questions about cryptocurrencies. The international contributor team uses the common law systems of the United Kingdom as a basis for the analysis, but also looks comparatively to other systems across the wider common law and civil law world to provide detailed examination of the legal problems encountered.
The discovery and development of effective medicines for the treatment of psychiatric disorders such as schizophrenia and depression has been heralded as one of the great medical achievements of the past century. Indeed, the profound impact of these medicines on our understanding of the pathophysiology underlying these diseases, the treatment of psychiatric patients and even our social perception of mental illnesses cannot be underestimated. However, there is still an urgent medical need for even more effective, safe and well-tolerated treatments. For example, currently available treatments for schizophrenia address mainly the positive symptoms and largely neglect the negative symptoms and cognitive disfunction which greatly impact overall morbidity. Similarly, whilst the current first line antidepressants show significantly improved side effect profiles compared to the first generation therapies, there still up to 40% of patients who are treatment resistant, and even in the patient population which responds well, the onset of action is slow at typically 2-3 weeks. The aim of this book is to provide the first point of call for those involved or just interested in this rapidly expanding and increasingly fragmented field of research and drug discovery. The editors will combine their wide ranging experience and extensive network of contacts with leading scientists and opinion leaders in this field to provide an authoritative reference text covering the evolution, major advances, challenges and future directions in drug discovery and medicinal chemistry for major psychiatric disorders.
From crystal structure prediction to totally empirical screening, the quest for new crystal forms has become one of the most challenging issues in the solid state science and particularly in the pharmaceutical world. In this context, multi-component crystalline materials like co-crystals have received renewed interest as they offer the prospect of optimized physical properties. As illustrated in this first book_ entirely dedicated to this emerging class of pharmaceutical compounds_ the outcome of such endeavours into crystal engineering have demonstrated clear impacts on production, marketing and intellectual property protection of active pharmaceutical ingredients (APIs). Indeed, co-crystallization influences relevant physico-chemical parameters (such as solubility, dissolution rate, chemical stability, melting point, hygroscopicity, a) and often offers solids with properties superior to those of the free drug. Combining both reports of the latest research and comprehensive overviews of basic principles, with contributions from selected experts in both academia and industry, this unique book is an essential reference, ideal for pharmaceutical development scientists and graduate students in pharmaceutical science."
Comprehensive Biomarker Discovery and Validation for Clinical Application provides the reader with an extensive introduction into all aspects of proteomics biomarker discovery, validation and development. It discusses the current status of science and technology, its limitations, bottlenecks as well as future development trends to improve the success rate of translating biomarker discovery into useful clinical tests. The most important feature of the book is to provide an overview of current technologies and the challenges encountered during biomarker discovery and validation, such as patient selection, sample handling, data processing, statistical analysis and registration and approval of validated biomarkers through European and US regulatory authorities. The authors introduce the reader to each of these topics in significant detail and provide examples or guidelines for best practice. There are prominent chapters included on biomarkers in translational and personalised medicine; an introduction to regulatory affairs and bring biomarkers to the market; biomarker discovery and the use of mass spectrometry based profiling platforms; MALDI imaging techniques in tissue-based biomarkers discovery and a clinical application study on the use of diagnostic assays for early diagnosis of heart failure using various proteomic methods. The book concludes with a final chapter on future trends in biomarker discovery and validation. The book targets a readership of industrial and academic researchers that are involved in biomarker discovery and validation or that manage biobanks, develop sample preparation methods, analytical profiling systems and bioinformatics tools. Common pitfalls and success stories in biomarker discovery are highlighted and guidelines for best practice are provided for the different parts of the procedure. The book will be an essential information resource for scientists working in the field.
Nuclear receptors (NR) are ligand-induced activated transcription factors that are involved in numerous biological processes. Since the 1990's when the first structures were determined by means of X ray diffraction, the number of NR structures has increased considerably. Moreover several "omics" projects (genomics, pharmcogenomics and proteomics) have opened up great opportunities for the discovery of new targets, the characterization of abnormal protein patterns, the selection of "tailored" drugs and the evaluation of drug efficacy even with a lack of structural data. Furthermore, structure-based drug design, computational methods for in silico screening and nanobiotechnology- based tools are simplifying this time-consuming and money-intensive research of lead compounds and, possibly, new drugs. Biological interactions such as those that occur between a protein and ligand are concerted events where flexible molecules interact. Thus understanding flexibility of large molecules or biological complexes is of primary importance to help define the right model to approximate the reality for drug discovery, virtual screening, food safety analysis, etc. NRs are known as flexible targets, with many structural similarities, in particular for their Ligand Binding Domain: these similarities could be assumed to share behavioural qualities that belong to this class of compounds. Thus to supply a possible, complete and exhaustive answer to questions about the behaviour of NRs, their interactions with new potential drugs, endocrine disruptors such as animal and human food toxins, food additives or industry residuals, it is mandatory to approach the problem from a different point of view: a molecular modelling approach, steered synthesis, and in vitro and in vivo tests, etc. The aim of this book is to provide a state of the art review on investigations into Nuclear Receptors.
Multi-target drug discovery (MTDD) is an emerging area of increasing interest to the drug discovery community. Drugs that modulate several targets have the potential for an improved balance of efficacy and safety compared to single targets agents. Although there are a number of marketed drugs that are thought to derive their therapeutic benefit by virtue of interacting with multiple targets, the majority of these were discovered accidentally. Written by world renowned experts, this is the first book to gather together knowledge and experiences of the rational discovery of multi-target drugs. It describes the current state of the art, the achievements and the challenges of the field and importantly the lessons learned by researchers to date and their application to future MTDD.
Due to injuries sustained in sports and in combat, interest in TBI has never been greater. Biomarkers for Traumatic Brain Injury will fulfil a gap in our understanding of what is occurring in the brain following injury that can subsequently be detected in biological fluids and imaging. This knowledge will be useful for all researchers and clinicians interested in the biochemical and structural sequelae underpinning clinical manifestations of TBI and help guide appropriate patient management. Current and prospective biomarkers for the assessment of traumatic brain injury (TBI), particularly mild TBI, are examined using a multidisciplinary approach involving biochemistry, molecular biology, and clinical chemistry. The book incorporates presentations from outstanding researchers and clinicians in the area and describes advanced proteomic and degradomic technologies in the development of novel biomarker assays. For practical purposes, the focus of this volume is on detection of blood-based biomarkers to improve diagnostic certainty of mild TBI in conjunction with radiological and clinical findings. It represents contributions from internationally-recognized researchers at the forefront of traumatic brain injury many of whom are recipients of grants and contracts from the United States Department of Defense for research specifically on developing diagnostic tests for TBI. The book will be essential reading for scientists, pharmacologists, chemists, medical and graduate students.
Kinase drug discovery remains an area of significant interest across academia and in the pharmaceutical industry. There are now around 13 FDA approved small molecule drugs which target kinases and many more compounds in various stages of clinical development. Although there have been a number of reviews/publications on kinase research, this book fills a gap in the literature by considering the current and future opportunities and challenges in targeting this important family of enzymes. The book is forward-looking and identifies a number of hot topics and key areas for kinase drug discovery over the coming years. It includes contributions from highly respected authors with a combined experience in the industry of well over 200 years, which has resulted in a book of great interest to the kinase field and across drug discovery more generally. Readers will gain a real insight into the huge challenges and opportunities which this target class has presented drug discovery scientists. The many chapters cover a wide breadth of topics, are well written and include high quality colour and black and white images. Topics covered include an outline of how medicinal chemistry has been able to specifically exploit this unique target class, along with reflections on the mechanisms of kinases inhibitors. Also covered is resistance to kinase inhibitors caused by amino acid mutations, case studies of kinase programs and reviews areas beyond protein kinases and beyond the human kinome. Also described are modern approaches to finding kinase leads and the book finishes with a reflection of how kinase drug discovery may progress over the coming years.
There are about 8 million deaths each year from neglected tropical diseases (NTDs) in the underdeveloped world, whilst drug discovery focus and practice is only recently taking on greater urgency and embracing the latest technologies. This unique book is a state of the art review of drug discovery in respect of NTDs and highlights best practice to guide the ongoing drug discovery effort and also to raise debate and awareness in areas that remain highly neglected. All the major diseases such as malaria, trypanosomatids and TB are covered, with a review of each disease and established compounds, new mechanistic classes and new horizons. Each chapter highlights the key science that has led to breakthroughs, with detailed assessment of the key medicinal chemistry involved, and critical appraisal of new emerging approaches. Later chapters highlight under publicized disease areas where the medical needs are neglected and research is very limited, to raise awareness. The editors, acknowledged experts in the field, have a wealth of experience in successful drug discovery practice and tropical diseases.
Pharmaceutical process research and development is an exacting, multidisciplinary effort but a somewhat neglected discipline in the chemical curriculum. This book presents an overview of the many facets of process development and how recent advances in synthetic organic chemistry, process technology and chemical engineering have impacted on the manufacture of pharmaceuticals. In 15 concise chapters the book covers such diverse subjects as route selection and economics, the interface with medicinal chemistry, the impact of green chemistry, safety, the crucial role of physical organic measurements in gaining a deeper understanding of chemical behaviour, the role of the analyst, new tools and innovations in reactor design, purification and separation, solid state chemistry and its role in formulation. The book ends with an assessment of future trends and challenges. The book provides a valuable overview of: both early and late stage chemical development, how safe and scaleable synthetic routes are designed, selected and developed, the importance of the chemical engineering, analytical and manufacturing interfaces, the key enabling technologies, including catalysis and biocatalysis, the importance of the green chemical perspective and solid form issues. The book, written and edited by experts in the field, is a contemporary, holistic treatise, with a logical sequence for process development and mini-case histories within the chapters to bring alive different aspects of the process. It is completely pharmaceutical themed, encompassing all essential aspects, from route and reagent selection to manufacture of the active compound. The book is aimed at both graduates and postgraduates interested in a career in the pharmaceutical industry. It informs them about the breadth of the work carried out in chemical research and development departments, and gives them a feel for the challenges involved in the job. The book is also of value to academics who often understand the drug discovery arena, but have far less appreciation of the drug development area, and are thus unable to advise their students about the relative merits of careers in chemical development versus discovery.
Intracellular cell signaling is a well understood process. However, extracellular signals such as hormones, adipokines, cytokines and neurotransmitters are just as important but have been largely ignored in other works. They are causative agents for diseases including hypertension, diabetes, heart disease, and arthritis so offer new, and often more approachable, targets for drug design. Aimed at medical professionals and pharmaceutical specialists, this book integrates extracellular and intracellular signalling processes and offers a fresh perspective on new drug targets. Written by colleagues at the same institution, but with contributions from leading international authorities, it is the result of close cooperation between the authors of different chapters. Readers are introduced to a new approach to disease causation by adipokines and toxic lipids. Heart disease, migraines, stroke, Alzheimer's disease, diabetes, cancer, and arthritis are approached from the perspective of prevention and treatment by alteration of extracellular signalling. Evidence is presented that the avoidance of toxic lifestyles can reduce the incidence of such illnesses and new therapeutic targets involving adipokines, ceramide and endocannabinoids are discussed.
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