Pursuing a career in biomedical research can be daunting, considering the stiffer competition and uncertain career prospects in academia. This book summarizes career advice gathered during in-depth interviews with 106 biomedical scientists who lead their own laboratories. The participating principal investigators are from 44 research institutions in 11 countries. This book is unique in that it provides a glimpse into the mindset of principal investigators. Here, the reader will learn about common thought patterns and values, as well as the range of opinions and ways of thinking to be found among a large group of active principal investigators - without having to read more than a hundred individual autobiographies. The book will benefit all PhD students who want to learn more about their supervisor's mindset in order to successfully complete their projects. It can help freshly graduated PhDs planning to pursue an academic career, and MDs contemplating a career in research, to decide whether they truly want to embark on this path. Lastly, it can offer young principal investigators a source of inspiration on how to succeed and achieve their goals.

Aromatase Inhibitors (AIs) treat postmenopausal estrogen receptor positive tumours, which constitute the majority of breast cancer patients. This comprehensive volume brings together the current knowledge from different relevant areas, including molecular mechanisms and translational aspects of drug resistance in AIs. Topics covered include research, experimental , and clinical data specifically focused on AI resistance in breast cancer. The volume will include three sections. The first section covers general knowledge about aromatase inhibitors, including regulation of aromatase genes, and structure and function of aromatase protein. The second section provides the detailed mechanisms of resistance to AIs, while the third section explores prediction of resistance and potential strategies to overcome resistance. Breast cancer is the most common female cancer and AIs significantly improve treatments outcomes compatibly to previously used endocrine treatments. However 10-15% of post-operative patients develop a relapse during adjuvant treatment with AIs; about 25-50% of the patients do not respond to AIs in neo-adjuvant or metastatic setting, and the majority of metastatic patients who initially respond develop resistance within 3 years. There is an important need to understand these mechanisms of resistance in order to develop methods of preventing or overcoming the resistance to AIs, which will ensure a more successful outcome in treating breast cancer.

This volume covers the topics presented at the 3rd International Conference on Tumor Microenvironment and Cellular Stress by an international community of researchers. The conference brings together scientists to discuss different cellular and animal models of tumor microenvironment study and identify common pathways that are candidates for therapeutic intervention; stimulate collaboration between groups that are more focused on elucidation of biochemical aspects of stress biology (e.g., HIF regulation) and groups that study the pathophysiological aspects of stress pathways or engaged in drug discovery; and critically evaluate novel targets for imaging or therapeutic intervention that would be of use to the tumor microenvironment community and pharmaceutical industry.

Medical research has been central to biomedicine in Africa for over a century, and Africa, along with other tropical areas, has been crucial to the development of medical science. At present, study populations in Africa participate in an increasing number of medical research projects and clinical trials, run by both public institutions and private companies. Global debates about the politics and ethics of this research are growing and local concerns are prompting calls for social studies of the "trial communities" produced by this scientific work. Drawing on rich, ethnographic and historiographic material, this volume represents the emergent field of anthropological inquiry that links Africanist ethnography to recent concerns with science, the state, and the culture of late capitalism in Africa.

Medical research involving human subjects has contributed to considerable advancements in our knowledge, and to medical benefits. At the same time the development of new technologies as well as further globalisation of medical research raises questions that require the attention of researchers from a range of disciplines. This book gathers the contributions of researchers from nine different countries, who analyse recent developments in medical research from ethical, historical, legal and socio-cultural perspectives. In addition to reflections on innovations in science such as genetic databases and the concept of "targeted therapy" the book also includes analyses regarding the ethico-legal regulation of new technologies such as human tissue banking or the handling of genetic information potentially relevant for participants in medical research. Country and culture-specific aspects that are relevant to human medical research from a global perspective also play a part. The value of multi- and interdisciplinary analysis that includes the perspectives of scholars from normative and empirical disciplines is a shared premise of each contribution.

Cancer is a multifaceted disease and overwhelmingly increasing experimental evidence has helped us to develop a deeper understanding of the role of signal transduction cascades in cancer development and progression. Tissue microarrays and next generation sequencing technologies have assisted us to gather missing pieces of jigsaw puzzle and we now know that deregulation of spatio-temporally controlled signaling cascades play fundamental role in metastasis and resistance against wide ranging therapeutics. This book offers a balanced overview of the rapidly emerging cutting edge research in molecular oncology and good source of knowledge for established oncologists, basic and medical students and pharmaceutical industry associated R&D departments.

Limiting genome replication to once per cell cycle is vital for maintaining genome stability. Although polyploidization is of physiologically importance for several specialized cell types, inappropriate polyploidization is believed to promote aneuploidy and transformation. A growing body of evidence indicates that the surveillance mechanisms that prevent polyploidization are frequently perturbed in cancers. Progress in the past several years has unraveled some of the underlying principles that maintain genome stability. This book brings together leaders of the field to overview subjects relating to polyploidization and cancer.

This book presents the fundamental physics of optical interferometry as applied to biophysical, biological and medical research. Interference is at the core of many types of optical detection and is a powerful probe of cellular and tissue structure in interfererence microscopy and in optical coherence tomography. It is also the root cause of speckle and other imaging artefacts that limit range and resolution. For biosensor applications, the inherent sensitivity of interferometry enables ultrasensitive detection of molecules in biological samples for medical diagnostics. In this book, emphasis is placed on the physics of light scattering, beginning with the molecular origins of refraction as light propagates through matter, and then treating the stochastic nature of random fields that ultimately dominate optical imaging in cells and tissue. The physics of partial coherence plays a central role in the text, with a focus on coherence detection techniques that allow information to be selectively detected out of incoherent and heterogeneous backgrounds. Optical Interferometry for Biology and Medicine is divided into four sections. The first covers fundamental principles, and the next three move up successive scales, beginning with molecular interferometry (biosensors), moving to cellular interferometry (microscopy), and ending with tissue interferometry (biomedical). An outstanding feature of the book is the clear presentation of the physics, with easy derivations of the appropriate equations, while emphasizing "rules of thumb" that can be applied by experimental researchers to give semi-quantitative predictions.

From the preface: "Neural Metabolism In Vivo aims to provide a comprehensive overview of neurobiology by presenting the basic principles of up-to-date and cutting-edge technology, as well as their application in assessing the functional, morphological and metabolic aspects of the brain. Investigation of neural activity of the living brain via neurovascular coupling using multimodal imaging techniques extended our understanding of fundamental neurophysiological mechanisms, regulation of cerebral blood flow in connection to neural activity and the interplay between neurons, astrocytes and blood vessels. Constant delivery of glucose and oxygen for energy metabolism is vital for brain function, and the physiological basis of neural activity can be assessed through measurements of cerebral blood flow and consumption of glucose and oxygen.... This book presents the complex physiological and neurochemical processes of neural metabolism and function in response to various physiological conditions and pharmacological stimulations. Neurochemical detection technologies and quantitative aspects of monitoring cerebral energy substrates and other metabolites in the living brain are described under the "Cerebral metabolism of antioxidants, osmolytes and others in vivo" section. Altogether, the advent of new in vivo tools has transformed neuroscience and neurobiology research, and demands interdisciplinary approaches as each technology could only approximate a very small fraction of the true complexity of the underlying biological processes. However, translational values of the emerging in vivo methods to the application of preclinical to clinical studies cannot be emphasized enough. Thus, it is our hope that advances in our understanding of biochemical, molecular, functional and physiological processes of the brain could eventually help people with neurological problems, which are still dominated by the unknowns." -- In-Young Choi and Rolf Gruetter

Angiogenesis is the growth of new blood vessels and is a key process which occurs during pathological disease progression. Excessive and damaging angiogenesis occurs in diseases such as cancer, diabetic retinopathies, age-related macular degeneration and atherosclerosis. In other diseases such as stroke and myocardial infarction, insufficient or improper angiogenesis results in tissue loss and ultimately higher morbidity and mortality. In this book we will begin by providing the reader with an overview of the process of angiogenesis including normal embryological development of blood vessels. The following chapters will each focus on a key angiogenic disease incorporating current scientific knowledge concerning the causes of activation of the "angiogenic switch," pathological consequences, current treatment options and future perspectives. Where appropriate, results from pre-clinical trials, novel imaging modalities and nanotechnological approaches will be incorporated into these sections. Finally, since it is now believed that the process of angiogenesis operated via different signalling mechanisms in different vascular beds, we will discuss our current understanding of this phenomenon. The target audience for this book would include researchers in all the basic sciences; post-graduate students at Universities and Institutes; pharmaceutical industries; clinicians working in vascular biology or tissue imaging; pathologists; neurologists; tumour biologists; ophthalmologists and cardiologists.

Cell-cell adhesion is fundamental for the development and homeostasis of animal tissues and organs. Adherens junctions (AJs) are the best understood cell-cell adhesion complexes. In this volume, internationally recognized experts review AJ biology over a wide range of organization; from atoms to molecules, to protein complexes, molecular networks, cells, tissues, and overall animal development. AJs have also been an integral part of animal evolution, and play central roles in cancer development, pathogen infection and other diseases. This book addresses major questions encompassing AJ biology. - How did AJs evolve? - How do cadherins and catenins interact to assemble AJs and mediate adhesion? - How do AJs interface with other cellular machinery to couple adhesion with the whole cell? - How do AJs affect cell behaviour and multicellular development? - How can abnormal AJ activity lead to disease? Valuable for both newcomers and experts in the field, this book offers a comprehensive resource for the research laboratory and a teaching tool for advanced undergraduate and graduate courses in cell and developmental biology.

Arterial chemoreceptors are unique structures which continuously monitor changes in arterial blood oxygen, carbon dioxide, glucose, and acid. Alterations in these gases are almost instantaneously sensed by arterial chemoreceptors and relayed into a physiological response which restores blood homeostasis. Arterial Chemoreception contains updated material regarding the physiology of the primary arterial chemoreceptor; the carotid body. Moreover, this book also explores tantalizing evidence regarding the contribution of the aortic bodies, chromaffin cells, lung neuroepithelial bodies, and brainstem areas involved in monitoring changes in blood gases. Furthermore this collection includes data showing the critical importance of these chemoreceptors in the pathophysiology of human disease and possible therapeutic treatments. This book is a required text for any researcher in the field of arterial chemoreception for years to come. It is also a critical text for physicians searching for bench-to-bedside treatments for heart failure, sleep apnea, and pulmonary hypertension.

The book is based on lectures presented on the International Summer School on Biophysics held in Croatia in September 2009. The advantage of the School is that it provides advanced training in very broad scope of areas related to biophysics contrary to other similar schools or workshops that are centered mainly on one topic or technique. In this volume, tenth in the row, the papers in the field of biophysics are presented. The topics are biological phenomena from single protein to macromolecular aggregations structure by using variant physical methods (NMR, EPR, FTIR, Mass Spectrometry, etc.). The interrelationship of supramolecular structures and their functions is enlightened by applications of principals of these physical methods in the biophysical and molecular biology context.

In this book, leading international experts analyze state-of-the-art advances in gene transfer vectors for applications in inherited disorders and also examine the toxicity profiles of these methods. The authors discuss the strengths and weaknesses of available vectors in the clinical setting, and specifically focus on the challenges and possible solutions that researchers are testing in order to improve the safety of gene therapy for genetic diseases. This comprehensive and authoritative overview of vector development is a necessary text for researchers, toxicologists, pharmacologists, molecular biologists, physicians, and students in these fields.

The seventh in Springer's landmark series of edited volumes on one of the highest-profile subjects in contemporary medicine and scientific endeavour, this volume sets out to cover a staggering range of research into the medical applications of stem cell research. While stem cells are the very stuff of life for multicellular organisms, including us humans, the cancer stem cell is a morbid entity with a robust resistance to therapies including conventional chemotherapy. This authoritative publication explains the regenerative potential of stem cells and their mesenchymal progeny, reviewing clinical applications of the latter in the treatment of cancer, diabetes and neurodegenerative pathologies. It covers the entire range of stem cells with known potential for therapeutic use, from human embryonic to germ cell-derived pluripotent stem cells and hematopoietic stem cells. The chapters also deal with the role of TGF-beta in propagating human embryonic stem cells, and in facilitating their differentiation. Featuring discussions of molecular signaling pathways that modulate mesenchymal stem cell self-renewal and much more, this book is certain to have broad appeal among academicians and physicians alike.

This book provides an up-to-date review of the general principles of and techniques for confirmatory adaptive designs. Confirmatory adaptive designs are a generalization of group sequential designs. With these designs, interim analyses are performed in order to stop the trial prematurely under control of the Type I error rate. In adaptive designs, it is also permissible to perform a data-driven change of relevant aspects of the study design at interim stages. This includes, for example, a sample-size reassessment, a treatment-arm selection or a selection of a pre-specified sub-population. Essentially, this adaptive methodology was introduced in the 1990s. Since then, it has become popular and the object of intense discussion and still represents a rapidly growing field of statistical research. This book describes adaptive design methodology at an elementary level, while also considering designing and planning issues as well as methods for analyzing an adaptively planned trial. This includes estimation methods and methods for the determination of an overall p-value. Part I of the book provides the group sequential methods that are necessary for understanding and applying the adaptive design methodology supplied in Parts II and III of the book. The book contains many examples that illustrate use of the methods for practical application. The book is primarily written for applied statisticians from academia and industry who are interested in confirmatory adaptive designs. It is assumed that readers are familiar with the basic principles of descriptive statistics, parameter estimation and statistical testing. This book will also be suitable for an advanced statistical course for applied statisticians or clinicians with a sound statistical background.

In the past two decades we have seen a surge forward in understanding the genetics and biochemistry underlying many pediatric orthopaedic disorders. A few projects have even progressed into the realm of clinical trials that are primarily aimed at controlling progressive disease. Meanwhile, genomic technology development has outpaced expectations and is enabling gene discovery for disorders that were previously intractable with traditional genetic methods. Included in this latter category are common disorders that display multigenic inheritance, sporadic disorders, and very rare conditions that are difficult to ascertain. Simultaneously, the study of pediatric orthopaedic disorders has been continuously refined and updated, highlighting a number of likely genetic conditions that are as yet unsolved. Molecular Genetics of Pediatric Orthopaedic Disorders updates researchers and clinicians of new developments of pediatric orthopaedic genetics. The chapters inform the audience on the revolution in new genomic methods and the impact this is having on potential study designs and the potential to discover genetic causes of many unsolved orthopaedic conditions. Recent examples have been included of pediatric orthopaedic conditions, both rare and common, that are being solved with these new methods. The book also educates pediatric orthopedic clinicians and geneticists on our understanding of the biology of "classic" genetic diseases that were derived from prior genetic studies. Chapters include biobanks and strategies for studying very rare disorders, genes and pathways causing primordial dwarfism, and notch signaling in congenital scoliosis, and more.

Signal transduction comprises the intracellular biochemical signals which induce the appropriate cell response to an external stimulus. The players in signal transduction are diverse, from small molecules as first messengers, to proteins, receptors, transcription factors, among many others. The different signaling pathways and the crosstalk between them originates the unique signaling profile of every cell type in the human body. The cell signaling specificity depends on several aspects including protein composition, subcellular localization and complexes and gene promoters. This textbook provides a comprehensive overview of the specific signaling pathways on a variety of human tissues. This information can be of great value for health science researchers, professionals and students to understand key pathways for tissue-specific functions in the plethora of signals, signals receptors, transducers and effectors. Chapter 3 and 15 are available open access under a Creative Commons Attribution 4.0 International License via link.springer.com.

Circadian rhythms are such an innate part of our lives that we rarely pause to speculate why they even exist. Some studies have suggested that the disruption of the circadian system may be causal for obesity and manifestations of Metabolic Syndrome (MetS). Shift-work, sleep-deprivation and bright-light-exposure at night are related to increased adiposity (obesity) and prevalence of MetS. It has been provided evidence of clock genes expression in human adipose tissue and demonstrated its association with different components of the MetS. Moreover, current studies are illustrating the particular role of different clock genes variants and their predicted haplotypes in MetS.

The purpose of Chronobiology and Obesity is to describe the mechanisms implicated in the interaction between chonodisruption and metabolic-related illnesses, such as obesity and MetS, with different approaches."

Adding to a vitally important cycle of publications covering the latest research developments in our understanding of neoplasms affecting the human central nervous system, this edition focuses on numerous aspects of pineal, pituitary, and spinal tumors. As with the previous volumes in the series, this latest work addresses a central imperative in cancer research the need to standardize classifications, written definitions and investigative guidelines in order to achieve a measure of shared objectivity among academics engaged in one of the most important medical endeavors of our era. It brings together the very latest work by oncologists, neurosurgeons, physicians, research scientists, and pathologists, providing the medical community with a wealth of data and results that, taken together, will advance the cause of cancer research. The volume synthesizes work on diagnosis, drug development, and therapeutic approaches that are typically scattered in a variety of journals and books. It features promising recent work in applying molecular genetics to clinical practice and evidence-based therapy, covering molecular profiling of tumors as well as a number of surgical treatments such as resection and radiosurgery. Together with its counterpart publications, it represents a much-needed central resource that will inform and guide future research efforts."

The book introduces the bioinformatics tools, databases and strategies for the translational research, focuses on the biomarker discovery based on integrative data analysis and systems biological network reconstruction. With the coming of personal genomics era, the biomedical data will be accumulated fast and then it will become reality for the personalized and accurate diagnosis, prognosis and treatment of complex diseases. The book covers both state of the art of bioinformatics methodologies and the examples for the identification of simple or network biomarkers. In addition, bioinformatics software tools and scripts are provided to the practical application in the study of complex diseases. The present state, the future challenges and perspectives were discussed. The book is written for biologists, biomedical informatics scientists and clinicians, etc. Dr. Bairong Shen is Professor and Director of Center for Systems Biology, Soochow University; he is also Director of Taicang Center for Translational Bioinformatics.

Bone marrow stem cells are the most transplanted cells worldwide. These cells are used as a replacement therapy for patients suffering from a diverse number of hematopoietic diseases and immunodeficiencies. However, the use of bone marrow cells in regenerative medicine has so far remained without much success. In the new era of pluripotent stem cells, great opportunities for establishing new therapies have opened up. The discovery of human embryonic stem cells and that of induced pluripotent (iPS) stem cells has made it possible to derive any desired tissues for regenerative medicine as iPS cell derived cells are only limited by the lack of established protocols that can be applied in humans. There is no doubt that stem cells present a new and innovative platform for establishing novel cell based therapies. The challenge is to establish new protocols that allow the successful differentiation of these cells into lineage committed cells. Embryonic Stem Cell Immunobiology: Methods and Protocols covers a variety of relevant topics, such as hematopoietic stem cells derived from ES cells, the interaction of these cells with natural killer cells or with cytotoxic T cells, and specific protocols for the derivation of hematopoietic cells and neuronal cells, to name a few. Written in the highly successful Methods in Molecular Biology series format, chapters contain introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and notes on troubleshooting and avoiding known pitfalls.

Authoritative and accessible, Embryonic Stem Cell Immunobiology: Methods and Protocols serves as an ideal guide to experts and non-experts interested in different aspects of stem cells.

This book covers such plants with edible modified storage subterranean stems (corms, rhizomes, stem tubers) and unmodified subterranean stem stolons, above ground swollen stems and hypocotyls, storage roots (tap root, lateral roots, root tubers), and bulbs, that are eaten as conventional or functional food as vegetables and spices, as herbal teas, and may provide a source of food additive or neutraceuticals. This volume covers selected plant species with edible modified stems, roots and bulbs in the families Iridaceae, Lamiaceae, Marantaceae, Nelumbonaceae, Nyctaginaceae, Nymphaeaceae, Orchidaceae, Oxalidaceae, Piperaceae, Poaceae, Rubiaceae and Simaroubaceae. The edible species dealt with in this work include wild and underutilized crops and also common and widely grown ornamentals.To help in identification of the plant and edible parts coloured illustrations are included. As in the preceding ten volumes, topics covered include: taxonomy (botanical name and synonyms); common English and vernacular names; origin and distribution; agro-ecological requirements; edible plant parts and uses; plant botany; nutritive, medicinal and pharmacological properties with up-to-date research findings; traditional medicinal uses; other non-edible uses; and selected/cited references for further reading. This volume has separate indices for scientific and common names; and separate scientific and medical glossaries.

Two sigma receptor subtypes have been proposed, sigma1 and 2. Much of our understanding of this system is based on biochemical and pharmacological characterization of the cloned sigma1 receptor subtype (Sigma1). It has become clear that sigma receptors are not canonical receptors. Sigma1 is highly conserved among mammalian species, however, it does not share significant homology with any other mammalian protein. Although a range of structurally diverse small molecules bind Sigma1 with high affinity, and it has been associated with a broad range of signaling systems, Sigma1 itself has no known signaling or enzymatic activity. The evolution of this field over nearly four decades has more recently led to a fundamental shift in the concept of "sigma receptors" to what may more accurately and generally be called sigma proteins. Largely based on traditional pharmacologic approaches, the Sigma1 protein has been associated with a broad range of signaling systems, including G-protein coupled receptors, NMDA receptors, and ion channels. Sigma proteins have been linked to a range of physiological processes, including intracellular calcium signaling, neuroprotection, learning, memory, and cognition. Emerging genetic, clinical, and mechanism focused molecular pharmacology data demonstrate the involvement of proteins in a range of pathophysiologies and disorders including neurodegenerative disease, pain, addiction, psychomotor stimulant abuse, and cancer. However, an understanding of the physiological role of sigma proteins has remained elusive. Emerging data associate Sigma1 with chaperone-like activities or molecular scaffold functions. This book aims to provide an updated perspective on this rapidly evolving field undergoing changes in fundamental concepts of key importance to the discipline of pharmacology. It focusses on the reported roles of sigma proteins in pathophysiology and on emergent therapeutic initiatives.

Neuropsychiatric disorders such as schizophrenia, mood disorders, Alzheimer s disease, epilepsy, alcoholism, substance abuse and others are one of the most debilitating illnesses worldwide characterizing by the complexity of the causes, and lacking the laboratory tests that may promote diagnostic and prognostic procedures. Recent advances in neuroscience, genomic, genetic, proteomic and metabolomic knowledge and technologies have opened the way to searching biomarkers and endophenotypes, which may offer powerful and exciting opportunity to understand the etiology and the underlying pathophysiological mechanisms of neuropsychiatric disorders. The challenge now is to translate these advances into meaningful diagnostic and therapeutic advances. This book offers a broad synthesis of the current knowledge about diverse topics of the biomarker and endophenotype strategies in neuropsychiatry.

The book is organized into four interconnected volumes: Neuropsychological Endophenotypes and Biomarkers (with overview of methodological issues of the biomarker and endophenotype approaches in neuropsychiatry and some technological advances), Neuroanatomical and Neuroimaging Endophenotypes and Biomarkers, Metabolic and Peripheral Biomarkers and Molecular Genetic and Genomic Markers . The contributors are internationally and nationally recognized researchers and experts from 16 countries. This four-volume handbook is intended for a broad spectrum of readers including neuroscientists, psychiatrists, neurologists, endocrinologists, pharmacologists, clinical psychologists, general practitioners, geriatricians, health care providers in the field of neurology and mental health interested in trends that have crystallized in the last decade, and trends that can be expected to further evolve in the coming years. It is hoped that this book will also be a useful resource for the teaching of psychiatry, neurology, psychology and mental health. "