Statistics is strongly tied to applications in different scientific disciplines, and the most challenging statistical problems arise from problems in the sciences. In fact, the most innovative statistical research flows from the needs of applications in diverse settings. This volume is a testimony to the crucial role that statistics plays in scientific disciplines such as genetics and environmental sciences, among others. The articles in this volume range from human and agricultural genetic DNA research to carcinogens and chemical concentrations in the environment and to space debris and atmospheric chemistry. Also included are some articles on statistical methods which are sufficiently general and flexible to be applied to many practical situations. The papers were refereed by a panel of experts and the editors of the volume. The contributions are based on the talks presented at the Workshop on Statistics and the Sciences, held at the Centro Stefano Franscini in Ascona, Switzerland, during the week of May 23 to 28, 1999. The meeting was jointly organized by the Swiss Federal Institutes of Technology in Lausanne and Zurich, with the financial support of the Minerva Research Foundation. As the presentations at the workshop helped the participants recognize the po tential role that statistics can play in the sciences, we hope that this volume will help the reader to focus on the central role of statistics in the specific areas presented here and to extrapolate the results to further applications."

The one and only comprehensive reference for all aspects of human genetics Unique in breadth and authority The fourth, completely revised edition of this classical reference and textbook presents a cohesive and up-to-date exposition of the concepts, results, and problems underlying theory and practice in human and medical genetics. In the 10 years since the appearance of the third edition, many new insights have emerged for understanding the genetic basis of development and function in human health and disease. Human genetics, with its emphasis on molecular concepts and techniques, has become a key discipline in medicine and the biomedical sciences. The fourth edition has been extensively expanded by new chapters on hot topics such as epigenetics, pharmacogenetics, gene therapy, cloning and genetic epidemiology. In addition a section giving an overview on the main model organisms (mouse, dog, worm, fly, yeast) used in human genetics research has been introduced. This book will be of interest to human and medical geneticists, scientists in all biomedical sciences, physicians and epidemiologists, as well as to graduate and postgraduate students who desire to learn the fundamentals of this fascinating field

After decades of systematic collection of data describing age-related changes in organisms, organs, tissues, cells and macromolecules, biogerontologists are now in a position to construct general principles of ageing and explore various possibilities of intervention using rational approaches. While not giving serious consideration to the claims made by charlatans, it cannot be ignored that several researchers are making genuine attempts to test and develop various means of intervention for the prevention and treatment of age-related diseases, for regaining the functional abilities and for prolonging the lifespan of experimental organisms. This book provides the most up-to-date information and a critical evaluation of a variety of approaches being tried for modulating aging and longevity, including dietary supplementation with antioxidants, vitamins and hormones, genetic engineering, life-style alterations, and hormesis through mild stress. The goal of research on ageing is not to increase human longevity regardless of the consequences, but to increase active longevity free from disability and functional dependence.

Cell culture based research is important for our understanding of biological processes at the cellular and molecular level. Using this approach, the previous decades have produced a wealth of mechanistic information in all areas of biomedical research. Such in vitro research, however, lacks the complexity of in vivo investigations, where many different cell types interact with each other in a normal, three-dimensional environment, with normal levels of cytokines and growth factors. Furthermore, complex human diseases, such as cancer, diabetes or chronic inflammation, can only be modeled in vivo. Due to its small size, its short reproduction time, and the possibility to introduce specific gene mutations, the mouse has become the favourite mammalian model organism to study in vivo function of genes during development and in disease. This book combines review articles on selected subjects presented at the symposium "Mouse as a Model Organism - From Animals to Cells", held in Rovaniemi, Finland, 2009. Among other topics, high-throughput phenotyping of mouse mutants, mouse phenotypes dependent on nature and nuture, and a spectrum of in vivo, ex vivo and in vitro methods to study cancer in mice are described. This book will give an excellent introduction to scientists interested in the use of mice as a model to understand complex biological questions in the post-genomic era. It will highlight the possibilities, but also discuss the current problems and shortcomings, to give a realistic view of the current state-of-art in this fascinating field of biomedical research.

In the past four years, many genetic loci have been implicated for BMI from the outcomes of genome-wide association studies (GWAS), primarily in adults. Insulin-induced gene 2 (INSIG2) was the first locus to be reported by this method to have a role in obesity but replication attempts have yielded inconsistent outcomes. The identification of the second locus, the fat mass- and obesity-associated gene (FTO), h has been more robustly observed by others. Studies from both FTO knock out and FTO overexpression mouse model support the fact that FTO is directly involved in the regulation of energy intake and metabolism in mice, where the lack of FTO expression leads to leanness while enhanced expression of FTO leads to obesity. Along with numerous other studies, a number of genetic variants have been established robustly in the context of obesity, giving us fresh insights into the pathogenesis of the disease. This book will give a comprehensive overview of efforts aimed at uncovering genetic variants associated with obesity, which have been particularly successful in the past 5 years with the advent of genome-wide association studies (GWAS). This book will cover this state of the art technology and its application to obesity in great detail. Topics covered will include genetics of childhood obesity, genetics of syndromic obesity, copy number variants and extreme obesity, co-morbidities of obesity genetics, and functional follow-up of genetic variants. "

Proceedings of a NATO ASI held in Erice, Italy, April 27-May 1, 1995.

Human pluripotent stem cells, including human embryonic stem cells and induced pluripotent stem cells, are a key focus of current biomedical research. The emergence of state of the art culturing techniques is promoting the realization of the full potential of pluripotent stem cells in basic and translational research and in cell-based therapies. This comprehensive and authoritative atlas summarizes more than a decade of experience accumulated by a leading research team in this field. Hands-on step-by-step guidance for the derivation and culturing of human pluripotent stem cells in defined conditions (animal product-free, serum-free, feeder-free) and in non-adhesion suspension culture are provided, as well as methods for examining pluripotency (embryoid body and teratoma formation) and karyotype stability. The Atlas of Human Pluripotent Stem Cells - Derivation and Culturing will serve as a reference and guide to established researchers and those wishing to enter the promising field of pluripotent stem cell research.

The present volume is a continuation of the EL.B.A. Forum Series, which was initiated in the spring of 1995 with the first volume, entitled From Neural Network and Biomolecular Engineering to Bioelectronics, in which a brief outline of modem bioelectron ics given as "the use of biological materials and biological architectures for information processing and sensing systems and devices down to molecular level. " The present volume highlights the aspects of advanced biotechnology and electronics originating from molecular manufacturing, which has been emerging as an independent branch of research. This volume appears in a crucial moment, when significant progress has already been made in this strategic field and when technologies derived from it are recognized as critical for the welfare of our society. In addition, acknowledging to the Italian Ministry of University and Scientific and Technological Research for launching the National Research Program "Technologies for Bioelectronics" in 1992 and for continuation of support of this advanced multidisciplinary research, we would like to acknowledge the support of the National Research Council of Italy through the "Molecular Manufacturing" CNR Strategic Project since 1994. The significant unique role of Technobiochip in the organization of the EL.B.A. Forums and in bringing to light the enormous industrial potential of bioelectronics is duly acknowledged, as well as its attraction and support of top level scientists to the series of EL.B.A. Forums of which this volume is part. Dr. Sergey Vakula of the EL.B.A."

Epigenetic Regulation of Cancer in Response to Chemotherapy, Volume 158 of the Advances in Cancer Research series, highlights new advances in the field, with this new volume presenting interesting chapters. Each chapter is written by an international board of authors.

The first libraries of complementary DNA (cDNA) clones were con structed in the mid-to-late 1970s using RNA-dependent DNA polymerase (reverse transcriptase) to convert poly A* mRNA into double-stranded cDNA suitable for insertion into prokaryotic vectors. Since then cDNA technology has become a fundamental tool for the molecular biologist and at the same time some very significant advances have occurred in the methods for con structing and screening cDNA libraries. It is not the aim of cDNA Library Protocols to give a comprehensive review of all cDNA library-based methodologies; instead we present a series of up-to-date protocols that together should give a good grounding of proce dures associated with the construction and use of cDNA libraries. In deciding what to include, we endeavored to combine up-to-date versions of some of the most widely used protocols with some very usefiil newer techniques. cDNA Library Protocols should therefore be especially useful to the investigator who is new to the use of cDNA libraries, but should also be of value to the more experienced worker. Chapters 1-5 concentrate on cDNA library construction and manipula tion, Chapters 6 and 7 describe means of cloning difficult-to-obtain ends of cDNAs, Chapters 8-18 give various approaches to the screening of cDNA libraries, and the remaining chapters present methods of analysis of cDNA clones including details of how to analyze cDNA sequence data and how to make use of the wealth of cDNA data emerging from the human genome project."

Over the past 10 years great progress has been made in the development of efficient techniques for both gene isolation and mapping. The identifica- tion and isolation of transcribed sequences from large chromosomal regions are central to the human genome mapping project. Techniques for isolating novel cDNAs have applications both in the overall construction and integra- tion of long-range physical and transcription maps and in the identification of disease genes. A number of different techniques for the isolation of cDNAs from mam- malian genomes have been developed, including screening "zoo" blots, the use of large genomic clones (YACs or cosmids) for hybridization against cDNA libraries, and CpG island mapping. More recently two highly efficient tech- niques have been introduced: exon trapping, based on the presence of exon splice sites, and direct selection, based on the enrichment of selected cDNAs using immobilized YACs or cosmids. Leading researchers in the field have contributed chapters detailing the practical procedures for these and other widely used methods. The most rapid progress presently being made in the field of gene isolation concerns the partial sequencing of cDNA clones from one or both ends to produce expressed sequence tags (ESTs). Indeed, by Octo- ber 1995, the EST division of Genbank (dbEST) contained a total of approxi- mately 270,000 human EST sequences accounting for almost half the number of sequence entries in Genbank.

Developments over the past few years have revealed the remarkable versatility of RNA in any compartment of the cell, tasks that had been thought to be exclusively in the realm of proteins and even beyond. The chapters in this book written by leading investigators in the field provide insight into various promising avenues where RNA and nucleic acid derivatives including antisense RNAs, such as siRNA, miRNAs, amplification/selection (SELEX) generated aptamers as well as ribozymes are at the threshold of impacting medicine.

Part of a review series that looks at trends in modern biology. This book covers aspects of bioprocessing and biotransformation, where knowledge, methods and expertise are required from chemistry, biochemistry, microbiology, genetics, chemical engineering and computer science.

In the last few years the major effect that RNAi has had in invertebrate systems like C.elegans and drosophila is beginning to take hold in mammalian systems through both single gene knockdown experiments and genome-scale screens. In the next decade, there will no doubt be both notable successes and failures as we attempt to apply this genetic tool to various biological problems for the first time in academia and industry. Through the introduction of RNAi, mammalian systems have finally gained admittance to the pantheon of model genetic systems.

A major success story of modem molecular biology is the development of technologies to clone and express specific genes. Current applications of recombinant gene products cover a wide spectrum, including gene therapy, production of bioactive pharmaceuticals, synthesis of novel biopolymers, agriculture and animal husbandry, and so on. Inherent in bringing these appli cations to fruition is the need to design "expression constructs" that will per mit the ready and specific detection and isolation of the defined recombinant gene products. Recombinant Protein Protocols grows out of the need for a laboratory manual on the detection and isolation of recombinantly expressed genes that covers both the background information and the practical laboratory recipes for these analyses. In this book, detailed and contemporary protocols are col lected to provide the reader with a wide-ranging number of methodologies to enhance the detection and isolation of their gene product(s) of interest. A large number of molecular tags and labels and their usage are described, including enzymes, ligand-binding moieties, immunodetectable molecules, as well as methods to detect interactive proteins, and gene expression-mediated alter ations in cellular activity. Chapters on in situ detection of gene expression deal with technologies that are currently being applied to the study of gene function and activity. Highlights of applications for recombinant gene expres sion technologies are provided to give readers exciting perspectives on the future of such technologies.

As the major task of sequencing the human genome is near completion and full complement of human genes are catalogued, attention will be focused on the ultimate goal: to understand the normal biological functions of these genes, and how alterations lead to disease states. In this task there is a severe limitation in working with human material, but the mouse has been adopted as the favored animal model because of the available genetic resources and the highly conserved gene conservation linkage organization. In just of ten years since the first gene-targeting experiments were p- formed in embryonic stem (ES) cells and mutations transmitted through the mouse germline, more than a thousand mouse strains have been created. These achievements have been made possible by pioneering work that showed that ES cells derived from preimplantation mouse embryos could be cultured for prolonged periods without differentiation in culture, and that homologous rec- bination between targeting constructs and endogenous DNA occurred at a f- quency sufficient for recombinants to be isolated. In the next few years the mouse genome will be systematically altered, and the techniques for achi- ing manipulations are constantly being streamlined and improved.

In 1970, Manfred Eigen initiated the study of the origin of self-reproducing systems of macromolecules and their evolution. Large-scale nucleotide sequencing (with computer methods) was introduced from 1977. The authors of this book, the first edition of which appeared (in Russian) in 1985, have been engaged in the research of the evolution of molecular genetic regulatory systems ever since those pioneering years. The book considers many fundamental problems of molecular biology, evolution, molecular genetic organization, the structure and function of macromolecules, always with the underlying motive of developing a unified theory. It describes many original, theoretical results as well as computational methods.

Recent work has revealed that stabilizing G-quadruplexes in telomeric DNA inhibits telomerase activity, providing impetus for the development of G-quartet-interacting drugs, while G-quartet-containing oligonucleotides have been recognized as a potent class of aptamers effective against STAT3 and other transcription factors implicated in oncogenesis, proving these guanine-quartets to be a vital and rich area for future study. In "G-Quadruplex DNA: Methods and Protocols", experts in the field present a collection of detailed techniques for studying G-quartet formation, dynamics, and molecular recognition. Written in the highly successful Methods in Molecular Biology (TM) series format, chapters include brief 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 cutting-edge, "G-Quadruplex DNA: Methods and Protocols "promises to be a useful resource for those familiar with G-quartets as well as an easy entry point for those researchers from diverse fields who are just developing an interest in the exciting implications of G-quadruplex DNA.

PCR Cloning Protocols, Second Edition, updates and expands Bruce White's best-selling PCR Cloning Protocols (1997) with the newest procedures for DNA cloning and mutagenesis. Here the researcher will find readily reproducible methods for all the major aspects of PCR use, including PCR optimization, computer programs for PCR primer design and analysis, and novel variations for cloning genes of special characteristics or origin, with emphasis on long distance PCR and GC-rich template amplification. Also included are both conventional and novel enzyme-free and restriction site-free procedures to clone PCR products into a range of vectors, as well as state-of-the-art protocols to facilitate DNA mutagenesis and recombination, and to clone the challenging uncharacterized DNA flanking a known DNA fragment.

The intersection of race, ethnicity and genomics has recently been a focus of debate and concern. The key areas of debate are pharmacogenomics and, to a lesser extent, racial profiling in the criminal justice system. The former poses the question as to whether certain "races" are genetically predisposed towards given diseases and whether they metabolize drugs differently; with the latter debating whether DNA analyses accurately identify the "race" of an individual. This book takes a different approach, while acknowledging the importance of these debates and their role in shaping what the issues are perceived to be in thinking about the intersection of race, ethnicity and genomics. We are interested in exploring the interconnections between race, ethnicity and nation and kinship, always bearing in mind that kinship, as a domain of human experience and a field of social study, has been reshaped by the genomic and biotechnological revolution. Peter Wade is Professor of Social Anthropology at the University of Manchester. His publications include Blackness and Race Mixture (1993), Race and Ethnicity in Latin America (1997), Music, Race and Nation: Musica Tropical in Colombia (2000), Race, Nature and Culture: An Anthropological Perspective (2002). His current research focuses on issues of racial identity, embodiment and new genetic and information technologies.

The current explosive progress in molecular biological research can be definitively traced to the development of molecular cloning technology. The ability to insert specific gene sequences into cloning vectors and their subse quent expansion is the cornerstone of modem molecular biology. A direct practical outcome of molecular cloning technology is its application to ex press specific recombinant genes. Currently, recombinant gene products are used in a wide spectrum of applications, including gene therapy, production of bioactive pharmaceuticals, synthesis of novel biopolymers, in agriculture and animal husbandry, and so on. A fundamental requirement for successful recombinant gene expression is the design of the cloning vector and the choice of the host organism for expression. Recombinant Gene Expression Protocols grows out of the need for a laboratory manual that provides the reader the background and rationale, as well as the practical protocols for the preparation of "expression constructs" and their introduction into appropriate host cells and/or organisms. The chap ters in this book are grouped by their expression hosts, including E. coli, yeast, mammalian cells, nonmammalian eukaryotes such as plants, Xenopus, and insects, as well as in transgenic organisms. In-depth information is presented on the important characteristics of expression cloning vectors and the various methods for efficiently introducing expression constructs into target cells and/ or organisms. Throughout Recombinant Gene Expression Protocols, the authors have consistently striven for a balanced presentation of both background informa tion and actual laboratory details.

Analysis of Genetic Association Studies is both a graduate level textbook in statistical genetics and genetic epidemiology, and a reference book for the analysis of genetic association studies. Students, researchers, and professionals will find the topics introduced in Analysis of Genetic Association Studies particularly relevant. The book is applicable to the study of statistics, biostatistics, genetics and genetic epidemiology. In addition to providing derivations, the book uses real examples and simulations to illustrate step-by-step applications. Introductory chapters on probability and genetic epidemiology terminology provide the reader with necessary background knowledge. The organization of this work allows for both casual reference and close study.

Since its invention and subsequent development nearly 20 years ago, po- merase chain reaction (PCR) has been extensively utilized to identify numerous gene probes in vitro and in vivo. However, attempts to generate complete and full-length complementary cDNA libraries were, for the most part, fruitless and remained elusive until the last decade, when simple and rapid methods were developed. With current decoding and potential application of human genome information to genechips, there are urgent needs for identification of functional significance of these decoded gene sequences. Inherent in bringing these app- cations to fruition is the need to generate a complete and full-length cDNA library for potential functional assays of specific gene sequences. Generation of cDNA Libraries: Methods and Protocols serves as a laboratory manual on the evolution of generation of cDNA libraries, covering both ba- ground information and step-by-step practical laboratory recipes for which p- tocols, reagents, operational tips, instrumentation, and other requirements are detailed. The first chapter of the book is an overview of the basics of generating cDNA libraries, which include the following: (a) the definition of a cDNA library, (b) different kinds of cDNA libraries, (c) differences between methods for cDNA library generation using conventional approaches and novel stra- gies, including reverse generation of RNA repertoires from cDNA libraries, and (d) the quality of cDNA libraries.

The effort to sequence the human genome is now moving toward a c- clusion. As all of the protein coding sequences are described, an increasing emphasis will be placed on understanding gene function and regulation. One important aspect of this analysis is the study of how transcription factors re- late transcriptional initiation by RNA polymerase II, which is responsible for transcribing nuclear genes encoding messenger RNAs. The initiation of Class II transcription is dependent upon transcription factors binding to DNA e- ments that include the core or basal promoter elements, proximal promoter elements, and distal enhancer elements. General initiation factors are involved in positioning RNA polymerase II on the core promoter, but the complex - teraction of these proteins and transcriptional activators binding to DNA e- ments outside the core promoter regulate the rate of transcriptional initiation. This initiation process appears to be a crucial step in the modulation of mRNA levels in response to developmental and environmental signals. Transcription Factor Protocols provides step-by-step procedures for key techniques that have been developed to study DNA sequences and the protein factors that regulate the transcription of protein encoding genes. This volume is aimed at providing researchers in the field with the well-detailed protocols that have been the hallmark of previous volumes of the Methods in Molecular (TM) Biology series.