Machine learning is concerned with the analysis of large data and multiple variables. However, it is also often more sensitive than traditional statistical methods to analyze small data. The first volume reviewed subjects like optimal scaling, neural networks, factor analysis, partial least squares, discriminant analysis, canonical analysis, and fuzzy modeling. This second volume includes various clustering models, support vector machines, Bayesian networks, discrete wavelet analysis, genetic programming, association rule learning, anomaly detection, correspondence analysis, and other subjects. Both the theoretical bases and the step by step analyses are described for the benefit of non-mathematical readers. Each chapter can be studied without the need to consult other chapters. Traditional statistical tests are, sometimes, priors to machine learning methods, and they are also, sometimes, used as contrast tests. To those wishing to obtain more knowledge of them, we recommend to additionally study (1) Statistics Applied to Clinical Studies 5th Edition 2012, (2) SPSS for Starters Part One and Two 2012, and (3) Statistical Analysis of Clinical Data on a Pocket Calculator Part One and Two 2012, written by the same authors, and edited by Springer, New York.

The use of proteomics to study complex diseases such as cardiovascular disease, the leading cause of death in developed countries, has grown exponentially in recent years. Proteomics is a rapidly expanding investigation platform in cardiovascular medicine and is becoming integrated and incorporated into cardiovascular research. The proteomics field continues to develop with major improvements in mass spectrometry instrumentation, methodology and data analysis. Heart Proteomics: Methods and Protocols complies a selection of techniques and methods that target the numerous processes implicated in the pathophysiology of heart. Chapters cover protocols and updated methods in the heart proteomic area with a particular focus on MS-based methods of protein and peptide quantification and the analysis of posttranslational modifications as well as descriptions of system biology approaches, which provide a better understanding of normal and pathological processes. Written in the successful Methods in Molecular Biology (TM) series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Heart Proteomics: Methods and Protocols is a representative selection of methods that will prove to be a useful resource for experienced proteomics practitioners and newcomers 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, number 124, covers emerging applications of molecular imaging to oncology, including molecular-genetic imaging, imaging the tumor microenvironment, tracking cells and vaccines in vivo, and more.

Since scientists began experimenting with green fluorescent proteins in the middle of the 1990s, these proteins have become one of the most important tools available to researchers in modern medicine and biology. By using them to illuminate other proteins that were previously invisible even under microscope, scientists are now able to observe facets of disease that would have otherwise gone undetected. Green fluorescent proteins are a part of over three million experiments a year, and are invaluable for tasks such as tracking HIV, breeding bird flu-resistant chickens, and confirming the existence of cancerous stem cells. In Illuminating Disease, Marc Zimmer introduces us to these revolutionary proteins, acquainting readers both with the researchers responsible for the proteins' discovery as well as their wide utility. The book details the history of genetically modified fluorescent parasites and viruses, which provide scientists with new information about the spread of diseases. Green fluorescent proteins have played crucial roles in the research of malaria, AIDS/HIV, swine and bird flu, dengue, cancer, and chagas. They allow scientists and doctors to understand these diseases better, by quite literally illuminating various microscopic pieces that otherwise would have gone unseen. The book is richly illustrated, showing the many visually striking uses of GFP. Many of these scans have won awards in biological imaging competitions. Illuminating Disease is an accessible and illustrated introduction to one of the most important developments in medical research of the last several decades.

Statistical Thinking for Non-Statisticians in Drug Regulation, Second Edition, is a need-to-know guide to understanding statistical methodology, statistical data and results within drug development and clinical trials. It provides non-statisticians working in the pharmaceutical and medical device industries with an accessible introduction to the knowledge they need when working with statistical information and communicating with statisticians. It covers the statistical aspects of design, conduct, analysis and presentation of data from clinical trials in drug regulation and improves the ability to read, understand and critically appraise statistical methodology in papers and reports. As such, it is directly concerned with the day-to-day practice and the regulatory requirements of drug development and clinical trials. Fully conversant with current regulatory requirements, this second edition includes five new chapters covering Bayesian statistics, adaptive designs, observational studies, methods for safety analysis and monitoring and statistics for diagnosis. Authored by a respected lecturer and consultant to the pharmaceutical industry, Statistical Thinking for Non-Statisticians in Drug Regulation is an ideal guide for physicians, clinical research scientists, managers and associates, data managers, medical writers, regulatory personnel and for all non-statisticians working and learning within the pharmaceutical industry.

Technological developments in the life sciences confront us with new facets of a Faustian seduction. Are we "playing God" more and more, as claimed by critical authors of modernity? Achievements in genetic research produce ethical dilemmas which need to be the subject of reflection and debate in modern societies. Denial of ambivalences that ethical dilemmas arouse constitutes a threat to societies as well as to individuals. The book presents a compilation of some of the results of the interdisciplinary European study "Ethical Dilemmas Due to Prenatal and Genetic Diagnostics" (EDIG), which investigated some of these dilemmas in detail in a field which is particularly challenging: prenatal diagnosis. When results from prenatal diagnosis show fetal abnormalities, women and their partners are confronted with ethical dilemmas regarding: the right to know and the right not to know; decision-making about the remainder of the pregnancy and the desire for a healthy child; responsibility for the unborn child, for its well-being and possible suffering; life and death. This book provides answers from an ethical, psychoanalytical and medical viewpoint.

Reviews in Fluorescence 2016, the tenth volume of the book serial from Springer, serves as a comprehensive collection of current trends and emerging hot topics in the field of fluorescence and closely related disciplines. It summarizes the year's progress in fluorescence and its applications, with authoritative reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Reviews in Fluorescence offers an essential reference material for any research lab or company working in the fluorescence field and related areas. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of fluorescence will find it an invaluable resource.

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.

Editors hope that Regenerative Biology of the Spine and Spinal Cord appeals to the nostalgic sentiments of investigators and intellectuals in that it can be held in hand and provide a broad survey of leading edge science. At the same time its chapters can be digitally acquired for those established in the field to refine particular knowledge interests or gaps. Most importantly, we ask the reader, whomever that may be, to peruse without prejudice as countless more chapters will have been written before total spinal regeneration is achieved.

Medicinal chemistry is both science and art. The science of medicinal chemistry offers mankind one of its best hopes for improving the quality of life. The art of medicinal chemistry continues to challenge its practitioners with the need for both intuition and experience to discover new drugs. Hence sharing the experience of drug research is uniquely beneficial to the field of medicinal chemistry. Drug research requires interdisciplinary team-work at the interface between chemistry, biology and medicine. Therefore, the topic-related series Topics in Medicinal Chemistry covers all relevant aspects of drug research, e.g. pathobiochemistry of diseases, identification and validation of (emerging) drug targets, structural biology, drugability of targets, drug design approaches, chemogenomics, synthetic chemistry including combinatorial methods, bioorganic chemistry, natural compounds, high-throughput screening, pharmacological in vitro and in vivo investigations, drug-receptor interactions on the molecular level, structure-activity relationships, drug absorption, distribution, metabolism, elimination, toxicology and pharmacogenomics. In general, special volumes are edited by well known guest editors.

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 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.

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.

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.

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.

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.