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The proposed volume provides both fundamental and detailed information about the computational and computational-experimental studies which improve our knowledge of how leaving matter functions, the different properties of drugs (including the calculation and the design of new ones), and the creation of completely new ways of treating numerical diseases. Whenever it is possible, the interplay between theory and experiment is provided. The book features computational techniques such as quantum-chemical and molecular dynamic approaches and quantitative structure-activity relationships. The initial chapters describe the state-of-the art research on the computational investigations in molecular biology, molecular pharmacy, and molecular medicine performed with the use of pure quantum-chemical techniques. The central part of the book illustrates the status of computational techniques that utilize hybrid, so called QM/MM approximations as well as the results of the QSAR studies which now are the most popular in predicting drugs' efficiency. The last chapters describe combined computational and experimental investigations.
This edited volume is a definitive text on adaptive clinical trial designs from creation and customization to utilization. As this book covers the full spectrum of topics involved in the adaptive designs arena, it will serve as a valuable reference for researchers working in industry, government and academia. The target audience is anyone involved in the planning and execution of clinical trials, in particular, statisticians, clinicians, pharmacometricians, clinical operation specialists, drug supply managers, and infrastructure providers. In spite of the increased efficiency of adaptive trials in saving costs and time, ultimately getting drugs to patients sooner, their adoption in clinical development is still relatively low. One of the chief reasons is the higher complexity of adaptive design trials as compared to traditional trials. Barriers to the use of clinical trials with adaptive features include the concerns about the integrity of study design and conduct, the risk of regulatory non-acceptance, the need for an advanced infrastructure for complex randomization and clinical supply scenarios, change management for process and behavior modifications, extensive resource requirements for the planning and design of adaptive trials and the potential to relegate key decision makings to outside entities. There have been limited publications that address these practical considerations and recommend best practices and solutions. This book fills this publication gap, providing guidance on practical considerations for adaptive trial design and implementation. The book comprises three parts: Part I focuses on practical considerations from a design perspective, whereas Part II delineates practical considerations related to the implementation of adaptive trials. Putting it all together, Part III presents four illustrative case studies ranging from description and discussion of specific adaptive trial design considerations to the logistic and regulatory issues faced in trial implementation.
Bringing together the expertise of leading key opinion leaders from pharmaceutical industry, academia, and regulatory agencies, this book provides a balanced and comprehensive coverage of practical considerations for adaptive trial design and implementation.
This book addresses important biomaterials which are commonly used to fabricate scaffolds and it describes two major protocols employed in scaffold fabrication. Tissue engineering or regenerative medicine aims at restoring ex-novo tissues and organs whose functionality has been compromised as a consequence of diseases or traumatic events. The innovative concept underlying tissue engineering is the use of autologous cells, obtained from a biopsy of the patient. Cells are seeded on a porous scaffold which has the role of supporting and guiding cells towards the development of tissue-like structures as well as providing a platform for the delivery under controlled condition of growth factor release, etc. The successful manufacture of scaffolds for tissue engineering applications is crucial. In this book, these biomaterials are discussed. The book also covers illustrated examples, structure and properties of scaffolds, cellular interactions and drug delivery.
This book, for the first time, comprehensively assembles and analyzes a large body of information on the role of the fundamental mechanism of the protein biosynthesis pathway, translation, in cancer biology. It systematically explores the function of the translation machinery and its regulation, including cell signaling, in the development, maintenance and progression of human cancer. The work presented here unveils the tremendous potential and applications of this vast and exciting branch of genetic, biochemical and molecular science in cancer medicine and drug development.
Chapters contributed by experts in the field take the reader on a journey that starts with a dissection of the translation machinery and its regulation in norm and cancer. Later chapters characterize etiological and pathogenetic roles that translation plays in specific cancer types. Various aspects of diagnostic, prognostic and therapeutic significance of the translation machinery and its control in cancer are discussed. Readers will discover the importance of the process of translation and its regulatory mechanisms in physiology and cancer biology.
The chapters and the numerous illustrations included here were contributed by expert scientists and clinicians from renowned academic and clinical establishments in Canada, the United States of America, the United Kingdom, Italy, France, Belgium, Spain, Germany and Australia.
The book conveys information and knowledge that may interest a broad range of students and scholars ranging from basic scientists to clinicians and drug developers seeking to better understand the protein synthesis and its aberrations in cancer biology and cancer medicine.
This book explores a novel technique for processing biodiesel using lipase immobilization by encapsulation and its physical properties, stability characteristics, and application in stirred tank and re-circulated packed bed immobilized reactors for biodiesel production. The enzymatic processing of biodiesel addresses many of the problems associated with chemical processing. It requires only moderate operating conditions and yields a high-quality product with a high level of conversion and the life cycle assessment of enzymatic biodiesel production has more favourable environmental consequences. The chemical processing problems of waste water treatment are lessened and soap formation is not an issue, meaning that waste oil with higher FFA can be used as the feedstock. The by product glycerol does not require any purification and it can be sold at higher price. However, soluble enzymatic processing is not perfect. It is costly, the enzyme cannot be recycled and its removal from the product is difficult. For these reasons, immobilized enzymatic process has been developed which retains the advantages of the soluble enzymatic process and reuse of the enzyme is possible which decreases the enzyme cost, the biodiesel produced does not contain any enzyme residue and the activity of the enzyme can be increased by immobilization. The drawbacks of the immobilized enzyme process are mass transfer limitation, enzyme leakage, the lack of a versatile commercial immobilized enzyme and some of immobilization methods involve toxic chemicals. To overcome the drawbacks of the immobilized enzyme, an attempt is made to use a degradable biopolymer ( -carrageenan) as a carrier for lipase immobilization.
This monograph summarizes the large amount of experimental data accumulated during many years of studying the functions of the blood system and its regulatory mechanisms under the action of diverse morbific factors within the models of pathological processes (e.g. immobilization stress, blood loss, inflammation, cytostatic and radiation myelosuppressions, experimental encephalopathies, neuroses, and spontaneous leucosis). These data are is analyzed with the understanding that hematopoietic tissue is an integrated system that can react to the challenges of both the internal and external environments. This analysis helped develop the theory of hematopoiesis control describing the regularities in the work of basic subdivisions of the hematopoietic tissue under normal and pathological conditions, as well as the performance and interaction of the local and long-ranged control systems. The monograph is recommended for Physiologists, Pathophysiologists, Hematologists, Oncologists, Pharmacologists and other professionals.
Cutting edge technologies can propel a simple finding in basic science to a concept that can be of immense value to the society. While applying novel techniques to unravel the mysteries of biological processes, an offshoot of applied branch emerged. This field, which is now widely referred to as Translational Research utilizes basic science findings and translates these findings into innovative concepts for the benefit of mankind. This branch of science has evolved into a multidisciplinary juggernaut encompassing all known fields of science as varied as biomedicine, environment, law, economics, sociology, etc. With the ever increasing interest in this branch and the dreams and aspirations that this field can bring, basic science researchers are now taking a bold step into this new realm, merging different fields of knowledge to come up with novel inventions. This book "Translational research in environmental and occupational stress" provides and insight into the research that led to discoveries, inventions and development of novel technologies which will have a tremendous impact on the future of mankind.
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.
Osteoporosis Research - Animal Models, presents in a very illustrative and practical manner, general methodologies of bone studies in animals, as well as the particular features of the most commonly used animal models in the field. Research in the field of osteoporosis has grown in recent years. This has resulted in significant advances in determining the causes of osteoporosis, assessing risk factors, and creating new treatment methods. The use of animal models provides important knowledge about pathological conditions that can eventually lead to the development of more effective clinical treatment of diseases in both humans and animals. Osteoporosis Research - Animal Models, is an essential tool for researchers in the bone field. This book aids researchers in selecting their appropriate model and highlights the experiments that can be strategically designed to optimize the potential of an animal to develop the cardinal features of osteoporosis in humans. This book addresses the importance of recent findings from animal models and their significance on the pathogenesis of osteoporosis in relation to human disease.
Reflecting over three decades of advances, "Epidermal Cells: Methods and Protocols, Third Edition" underscores these advances in our understanding of epidermal biology with updated and entirely new protocols that compliment and extend the earlier edition. The inclusion of protocols useful for both in vitro and in vivo studies reflects many useful developments in the field. 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.
Dependable and easy to follow, "Epidermal Cells: Methods and Protocols, Third Edition" serves researchers working to accelerate the work in this vital field of study.
The integrin family is composed of 24 members and approximately ten years ago (2003) we published a book devoted to the nine I domain integrin subunits. In this second edition, I am pleased that most of the original authors have been able to contribute to the updated version.
I domain containing integrins include collagen receptors and leukocyte receptors. In 2003 the knockout mouse phenotypes for all of the I domain integrins had not yet been published; they are now, and are summarized and discussed in this edition.
Interestingly, a recent 10 integrin mutation in dogs has indicated that collagen-binding integrins in the musculoskeletal system might have much more severe phenotypes in larger animals/humans compared to the mild integrin phenotypes observed in collagen-binding integrin deficient mice. This finding is further discussed in the book.
In the cancer field, the microenvironment is taking center stage, and here collagen receptors on fibroblasts are predicted to play important roles in paracrine signaling, in regulating tissue stiffness and matrix remodeling.
New technologies, new mouse models in combination with analyses of I integrins in larger animals/humans are thus predicted to increase our knowledge about this group of receptors. With this in mind we look forward to another 10 years of research with I domain integrins.
The chapters in this volume present the latest developments in medicine and biology. Chapters One describes the oxidative stress in disease and health, as well as the action of classic and new antioxidants. Chapter Two examines an investigation by big data analysis of the Urban Heat Island (UHI) effect on human health problems. Chapter Three provides a literature review of the associations between sedentary behaviour and health-related outcomes in Japan. Chapter Four assesses non-specific chronic low back pain and reviews management strategies. Chapter Five studies scleroderma and its mythological background. Chapter Six reviews the possible mechanisms of 5-HT and their metabolites as common protectors against oxidative stress produced by animal venoms. Chapter Seven focuses on the effect of broad bean true mosaic virus (BBTMV) and salicylic acid (SA) treatments on the concentrations of photosynthetic pigments, total phenolics content, protein contents and the yield of susceptible and tolerance broad bean cultivars. Chapter Eight reviews the photochemical (photooxidative) activity of xanthone itself and the preventive effect of xanthone derivatives on photosensitised DNA damage.
The diversity of RNAs inside living cells is amazing. We have known of the more "classic" RNA species: mRNA, tRNA, rRNA, snRNA and snoRNA for some time now, but in a steady stream new types of molecules are being described as it is becoming clear that most of the genomic information of cells ends up in RNA. To deal with the enormous load of resulting RNA processing and degradation reactions, cells need adequate and efficient molecular machines. The RNA exosome is arising as a major facilitator to this effect. Structural and functional data gathered over the last decade have illustrated the biochemical importance of this multimeric complex and its many co-factors, revealing its enormous regulatory power. By gathering some of the most prominent researchers in the exosome field, it is the aim of this volume to introduce this fascinating protein complex as well as to give a timely and rich account of its many functions. The exosome was discovered more than a decade ago by Phil Mitchell and David Tollervey by its ability to trim the 3'end of yeast, S. cerevisiae, 5. 8S rRNA. In a historic account they laid out the events surrounding this identification and the subsequent birth of the research field. In the chapter by Kurt Januszyk and Christopher Lima the structural organization of eukaryotic exosomes and their evolutionary counterparts in bacteria and archaea are discussed in large part through presentation of structures.
This volume contains 29 engrossing chapters contributed by worldwide, leading research groups in the field of chemical biology. Topics include pre-biology; the establishment of the genetic code; isomerization of RNA; damage of nucleobases in RNA; the dynamic structure of nucleic acids and their analogs in DNA replication, extra- and intra-cellular transport; molecular crowding by the use of ionic liquids; new technologies enabling the modification of gene expression via editing of therapeutic genes; the use of riboswitches; the modification of mRNA cap regions; new approaches to detect appropriately modified RNAs with EPR spectroscopy and the use of parallel and high-throughput techniques for the analysis of the structure and new functions of nucleic acids. This volume discusses how chemistry can add new frontiers to the field of nucleic acids in molecular medicine, biotechnology and nanotechnology and is not only an invaluable source of information to chemists, biochemists and life scientists but will also stimulate future research.
This book discusses how biological molecules exert their function and regulate biological processes, with a clear focus on how conformational dynamics of proteins are critical in this respect. In the last decade, the advancements in computational biology, nuclear magnetic resonance including paramagnetic relaxation enhancement, and fluorescence-based ensemble/single-molecule techniques have shown that biological molecules (proteins, DNAs and RNAs) fluctuate under equilibrium conditions. The conformational and energetic spaces that these fluctuations explore likely contain active conformations that are critical for their function. More interestingly, these fluctuations can respond actively to external cues, which introduces layers of tight regulation on the biological processes that they dictate. A growing number of studies have suggested that conformational dynamics of proteins govern their role in regulating biological functions, examples of this regulation can be found in signal transduction, molecular recognition, apoptosis, protein / ion / other molecules translocation and gene expression. On the experimental side, the technical advances have offered deep insights into the conformational motions of a number of proteins. These studies greatly enrich our knowledge of the interplay between structure and function. On the theoretical side, novel approaches and detailed computational simulations have provided powerful tools in the study of enzyme catalysis, protein / drug design, protein / ion / other molecule translocation and protein folding/aggregation, to name but a few. This work contains detailed information, not only on the conformational motions of biological systems, but also on the potential governing forces of conformational dynamics (transient interactions, chemical and physical origins, thermodynamic properties). New developments in computational simulations will greatly enhance our understanding of how these molecules function in various biological events.
In recent years, inorganic polymers have attracted much attention in nano-biomedicine, in particular in the area of regenerative medicine and drug delivery. This growing interest in inorganic polymers has been further accelerated by the development of new synthetic and analytical methods in the field of nanotechnology and nanochemistry. Examples for biomedical inorganic polymers that had been proven to exhibit biomedical effects and/or have been applied in preclinical or clinical trials are polysilicate / silica glass (such as naturally formed "biosilica" and synthetic "bioglass") and inorganic polyphosphate. Some members of the mentioned biomedical inorganic polymers have already been applied e.g. as "bioglass" for bone repair and bone tissue engineering, or they are used in food processing and in dental care (inorganic polyphosphates). However, there are a number of further biological and medicinal properties of these polymers, which have been elucidated in the last few years but not yet been applied for treatment of humans. In addition to polysilicates and polyphosphate, there are a series of other inorganic polymers including polyarsenate and polyvanadate, whose biological / biomedical properties have been only marginally studied so far. Moreover, the combined application of inorganic polymers and organic polymeric molecules (formation of organic-inorganic hybrid materials) provides a variety of new materials with novel property combinations and diverse applications in nanomedicine. The planned book summarizes the present state of knowledge on a large group of inorganic polymers that had hitherto been mainly considered with regard to their chemistry but not comprehensively reviewed with respect to their potential biomedical applications.
This book provides readers with the latest developments in neurosciences research. Chapter One reviews the changes that occur in the muscle and neuromuscular junctions following nerve injury and discusses possible strategies to prevent muscle atrophy. Chapter Two focuses on the contribution of the anterior cingulate cortex in pain processing. Chapter Three discusses the role of the anterior cingulate cortex in the arising of awareness deficits in neurocognitive disorder, acquired brain injuries, mood disorders and psychosis. Chapter Four discusses the relationship between neuroplasticity and cognitive empowerment. Chapter Five investigates if cognitive empowerment through Eye Tracker technologies increases both neuropsychological and neurophysiological measures in patients with Rett Syndrome (RS).
This book provides new research insights on rare diseases. Chapter One reviews the use of patients' registries as a key tool in rare disease management. Chapter Two discusses the worldwide experience with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with rare abdominal and pelvic neoplasms with peritoneal metastases that should be evaluated for long-term benefit. Chapter Three explores the contribution of psychology-related research on Congenital Anomalies (CAs) from the analysis of international scientific literature.
The authors have shown recently that for the two types of adult stem cells (hematopoietic stem cells and intestinal epithelium stem cells), the "ischemia/reperfusion" reaction can be developed in vivo. The damaging action of this reaction onto stem cells can be diminished by an injection of a source of NO-radicals into the animal's body during reperfusion, since NO-radicals are capable of decreasing the negative effect of radicals produced after oxygen access into the ischemic tissues. The authors believe that these data may be used in the development of new approaches for the protection of cell systems of organism renewal after the damaging action of various agents.
It is clear that many fascinating problems still remain to be addressed in parasite transmission modelling, from better understanding of transmission processes and natural history of infection to investigating the impact of ecological and spatial scales, climate change, host immunity and social behaviour, parasite-host evolutionary dynamics and parasite community ecology on parasite transmission. This book captures some of the advances made in recent years and provides indications of ways forward for addressing these questions by shedding light on developments in conceptual frameworks and modelling tools as well as the emergence of new data forms for aiding model construction, testing and analysis. Another important advance has been the parallel development of robust computationally-intensive statistical methods to allow model testing and parameterization by aiding the fitting of models to complex data. This is an exciting area of work, which we believe will broaden the scope of mathematical modelling in investigating parasite transmission processes. In particular, we expect this advance will now allow modellers to begin the successful development and analysis of mechanistically-rich models of parasite transmission that will facilitate better integration of the variety of mechanisms increasingly recognized as important in simultaneously affecting transmission, including abiotic processes, trophic and evolutionary interactions, movement in space, and behaviour and even physiology of the individual. We foresee a continuing bright future for using mathematical modelling to clarify parasite transmission dynamics and address problems related to effective parasite control. Ultimately, through this improved application of models to research and management, we expect that parasite control would be an achievable goal bringing benefits to a vast number of our fellow human beings.
Utility of Insects for Studying Human Pathogens and Evaluating New Antimicrobial Agents, by Yan Wang, De-Dong Li, Yuan-Ying Jiang and Eleftherios Mylonakis. Galleria Mellonella as a Model Host to Study Gut Microbe Homeostasis and Brain Infection by the Human Pathogen Listeria Monocytogenes, by Krishnendu Mukherjee, Ramya Raju, Rainer Fischer and Andreas Vilcinskas. Drosophila as a Model to Study Metabolic Disorders, by Julia Hoffmann, Renja Romey, Christine Fink and Thomas Roeder. The Fruit Fly Drosophila melanogaster as a Model for Aging Research, by Annely Brandt and Andreas Vilcinskas. Drosophila and the Hallmarks of Cancer, by Theodoulakis Christofi and Yiorgos Apidianakis. The red flour beetle Tribolium castaneum as a model to monitor food safety and functionality, by Stefanie Grunwald, Iris V. Adam, Ana-Maria Gurmai, Ludmila Bauer, Michael Boll, and Uwe Wenzel. Identification and Bioanalysis of Natural Products from Insect Symbionts and Pathogens, by Alexander O. Brachmann and Helge B. Bode. Antiparasitic Peptides, by Jette Pretzel, Franziska Mohring, Stefan Rahlfs and Katja Becker.
Molecular pathology is based on the emergence of new techniques that greatly enhance the diagnostic accuracy when facing with challenging differential diagnoses. In addition, new molecular techniques are entering the clinical arena for their value in predicting therapy response and tumor prognosis. This book provides a guide for the practicing pathologist and for both pathology residents and fellows during the daily sign-out of challenging cases. The book is organized by anatomical systems and provides a detailed description of molecular tests that may help in the diagnosis. Furthermore, a description of the current molecular tests required to identify patients for treatment is offered. The application of molecular pathology techniques to the clinical practice has already shown its usefulness and the number of such tests is growing exponentially as more molecular targets are discovered. Molecular Pathology and Diagnostics of Cancer will give practicing and training pathologists an up-to date resource to guide the correct management of pathology cases requiring molecular testing.
This book presents original results on the leading edge of cancer research. Chapter One presents an overview of the opportunities and challenges that influence the participation of personalised approach of giving the right drug at the right dose to the right patient. Chapter Two examines malignant mesothelioma. Chapter Three reviews the role of heat-shock proteins and chaperonins in the pathogenesis and progression of cancer. Chapter Four discusses the biosynthesis of LeX family glycosphingolipids and its gene regulation. Chapter Five summarises how chromosome segregation is accurately controlled and how spindle assembly checkpoint (SAC) monitors this process to maintain segregation fidelity. Chapter Six reviews significant novel findings and the early clinical development of a CD26-targeted therapy for malignant pleural mesothelioma (MPM), and advances that can lead to a more hopeful future for MPM patients. Chapter Seven reviews the pathophysiology and novel treatment strategies in management of peripheral T-Cell lymphoma. Chapter Eight discusses the confirmation behind a role for metformin in cancer therapy and its prospective molecular mechanisms of action. Chapter Nine highlights the role Ganoderma lucidum and its constituents in cancer signaling. Chapter Ten studies the footprint of Ganoderma lucidum in receptor tyrosine kinases.
The chapters in this volume present the latest developments in medicine and biology. Chapters One and Two review the clinical uses, functionality, mechanisms of action and adverse reactions of Andrographis Paniculata. Chapter Three gives an overview of the chemical structure and biosynthesis of triacylglycerols in vegetables, and their health benefits. Chapter Four discusses long-chain fatty acids in triacylglycerol stores and physical performance. Chapter Five presents the different methods for determining skin color. Chapter Six discusses the imaging of chronic pancreatitis. Chapter Seven examines the influence of gingivitis on abdominal aortic aneurysms. Chapter Eight provides a review of the existing research on measurement, rates, correlates, and consequences of sedentary behavior in Multiple Sclerosis. Chapter Nine focuses on injury and recovery of the periodontal ligament.
Being diagnosed with Systemic Lupus Erythematosus (SLE) can be a severe disappointment, and life after diagnosis can be defined as an existence filled with uncertainty as to the short-and long-term impact of the disease. SLE is a chronic multi-system autoimmune disease that is persistent and recurrent and has the potential of becoming life threatening. The manifestations and severity of the disease varies between individuals. SLE can potentially influence nearly all of the bodys organ systems. In this book, Chapter One reviews, Raynauds phenomenon (RP), one of the nonspecific skin changes that occur in SLE. Chapter Two presents the debate on the causes of fatigue in SLE and factors that increase fatigue. Chapter Three reviews and illustrates the important findings of musculoskeletal diseases in SLE. Chapter Four examines SLE in young adults and reviews information about the pain, social impact, and interventions to improve functioning of these young adults.
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