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.

Strategy and Statistics in Clinical Trials deals with the research processes and the role of statistics in these processes. The book offers real-life case studies and provides a practical, how to guide to biomedical R&D. It describes the statistical building blocks and concepts of clinical trials and promotes effective cooperation between statisticians and important other parties. The discussion is organized around 15 chapters. After providing an overview of clinical development and statistics, the book explores questions when planning clinical trials, along with the attributes of medical products. It then explains how to set research objectives and goes on to consider statistical thinking, estimation, testing procedures, and statistical significance, explanation and prediction. The rest of the book focuses on exploratory and confirmatory clinical trials; hypothesis testing and multiplicity; elements of clinical trial design; choosing trial endpoints; and determination of sample size. This book is for all individuals engaged in clinical research who are interested in a better understanding of statistics, including professional clinical researchers, professors, physicians, and researchers in laboratory. It will also be of interest to corporate and government laboratories, clinical research nurses, members of the allied health professions, and post-doctoral and graduate students.

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.

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.

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.

In the past several years, there has been an explosion in the ability of biologists, molecular biologists and biochemists to collect vast amounts of data on their systems. This volume presents sophisticated methods for estimating the thermodynamic parameters of specific protein-protein, protein-DNA and small molecule interactions. The use of thermodynamics in biological research is used as an energy book-keeping system. While the structure and function of a molecule is important, it is equally important to know what drives the energy force. These methods look to answer: What are the sources of energy that drive the function? Which of the pathways are of biological significance?

As the base of macromolecular structures continues to expand through powerful techniques of molecular biology, such as X-ray crystal data and spectroscopy methods, the importance of tested and reliable methods for answering these questions will continue to expand as well.

* Elucidates the relationships between structure and energetics and their applications to molecular design, aiding researchers in the design of medically important molecules * Provides a "must-have" methods volume that keeps MIE buyers and online subscribers up-to-date with the latest research * Offers step-by-step lab instructions, including necessary equipment, from a global research community "

The combination of faster, more advanced computers and more quantitatively oriented biomedical researchers has recently yielded new and more precise methods for the analysis of biomedical data. These better analyses have enhanced the conclusions that can be drawn from biomedical data, and they have changed the way that experiments are designed and performed. This volume, along with the 2 previous "Computer Methods" volumes for the "Methods in Enzymology" serial, aims to inform biomedical researchers about recent applications of modern data analysis and simulation methods as applied to biomedical research.

* Presents step-by-step computer methods and discusses the techniques in detail to enable their implementation in solving a wide range of problems * Informs biomedical researchers of the modern data analysis methods that have developed alongside computer hardware *Presents methods at the "nuts and bolts" level to identify and resolve a problem and analyze what the results mean

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

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.

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.

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.

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.

"Advances in Cancer Research" provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics.

In the past decades our understanding of stem cell biology has increased tremendously. Many types of stem cells have been discovered in tissues of which everyone presumed were unable to regenerate in adults; these include particularly the heart and the brain. There is vast interest in stem cells from biologists and clinicians who see the potential for regenerative medicine and future treatments for chronic diseases like Parkinson, diabetes and spinal cord lesions based on the use of stem cells and entrepreneurs in biotechnology who expect new commercial applications ranging from drug discovery to transplantation therapies.

As is often the case in science, many early claims turned out to be different from those expected. Embryonic stem cell therapies have not moved rapidly into clinical practice. Adult stem cells certainly have given certain degrees of success but not nearly to the extent that advocates would have wished for. Some claims of early successes in adult stem cell therapies have not been sustained in double-blinded, randomized clinical trials. Some claims are now close to routine therapy. Some of the claims not supported by evidence have nevertheless reached private clinical practice so that "stem cell tourism" is beginning to reach exaggerated proportions.

This book provides the reader background information on stem cells in a clear and well-organized manner. It provides the non-stem cell expert with an understandable review of the history, current state of affairs, and facts and fiction of the promises of stem cells. It distinguishes itself from the multiplicity of websites on the subject of stem cells by being scientifically, politically and ethically neutral, explaining pros and cons for stem cells of every sort with the intention of reaching a wide readership ranging from advanced students and patient advocacy groups to clinicians, specialists and early phase medics in training. By providing the background scientific and social information, it provides readers with the information they require to form their own opinions on the use of stem cells on the basis of facts rather than hype.

* Explains in straightforward, non-specialist language the basic biology of stem cells and their applications in modern medicine and future therapy

* Includes extensive coverage of adult and embryonic stem cells both historically and in contemporary practice

* Richly illustrated to assist in understanding how research is done and the current hurdles to clinical practice"

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.

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.

"Advances in Cancer Research" provides invaluable information on the exciting and fast-moving field of cancer research. Here, once again, outstanding and original reviews are presented on a variety of topics.

This volume comprehensively covers new technologies and methodologies that have appeared for the study of mouse development.

This volume is an update of volume 225 of MIE, "Guide to Techniques in Mouse Development," edited by P.M. Wassarman and M.L. DePamphilis and published in 1993. During the past 17 years many new technologies or methodologies have appeared for the study of mouse development and this volume comprehensively covers these, including: new techniques for the cryopreservation of gametes and embryos, production of transgenic and null (knockout) animals (use of ES cells), generation of conditional/inducible mutant animals, use of gene-trap mutagenesis, analysis of allele-specific expresion, use of new reporter constructs, humanizing of transgenic animals, transcript profiling of mouse development, imaging of mouse development, rederivation of animals and use of mouse genomics.

This volume comprehensively covers new technologies and methodologies that have appeared for the study of mouse development.

This volume is Part B of an update of volume 225, "Guide to Techniques in Mouse Development," edited by P.M. Wassarman and M.L. DePamphilis and published in 1993.

Comprehensively covers new techniques for the cryopreservation of gametes and embryos, production of transgenic and null (knockout) animals (use of ES cells), generation of conditional/inducible mutant animals, use of gene-trap mutagenesis, analysis of allele-specific expression, use of new reporter constructs, humanizing of transgenic animals, transcript profiling of mouse development, imaging of mouse development, and rederivation of animals and use of mouse genomics.

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.

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."