It has become clear that tumors result from excessive cell proliferation and a corresponding reduction in cell death caused by the successive accumulation of mutations in key regulatory target genes over time. During the 1980s, a number of oncogenes were characterized, whereas from the 1990s to the present, the emp- sis has shifted to tumor suppressor genes (TSGs). It has become clear that oncogenes and TSGs function in the same pathways, providing positive and negative growth regulatory activities. The signaling pathways controlled by these genes involve virtually every process in cell biology, including nuclear events, cell cycle, cell death, cytoskeletal, cell membrane, angiogenesis, and cell adhesion effects. Mu- tions in tumor suppressor genes have been identified in familial cancer syndromes, and the same genes in many cases have been found to be mutationally inactivated in sporadically occurring cancers. In their normal state, TSGs control cancer development and progression, as well as contribute to the sensitivity of cancers to a variety of therapeutics. Understanding the classes of TSGs, the biochemical pa- ways they function in, and how they are regulated provides an essential lesson in cancer biology. We cannot hope to advance our current knowledge and to develop new and more effective therapies without understanding the relevant pathways and how they influence the present approaches to therapy. Moreover, it is important to be able to access not only the powerful tools now available to discover these genes, but also their links to cell biology and growth control.

Confocal Microscopy: Methods and Protocols, Second Edition takes the researcher from the bench top through the imaging process, to the page. Protocols for the preparation of tissues from many model organisms including worms, flies and mice have been included as well as chapters on confocal imaging of living cells, three dimensional analysis, and the measurement and presentation of confocal images for publication. Emphasis has been placed on the laser scanning confocal microscope since this is still the instrument used for most routine applications. The current generation of modern confocal instruments produces optical sections of cells and tissues that are free of out-of-focus fluorescence with reduced chances of artifacts from the techniques of specimen preparation. This allows the imaging of living specimens and measurements of physiological events within cells. Confocal microscopy has become essential in many fields of contemporary biomedical research where a light microscope is required for imaging fluorescently labeled cells and tissues, especially cell biology, developmental biology, neurobiology, and pathology. Written in the successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible protocols, and notes on troubleshooting and avoiding known pitfalls. Authoritative and easily accessible, Confocal Microscopy: Methods and Protocols, Second Edition is aimed primarily, but not exclusively, at the novice user with pointers to more advanced techniques.

Bridging the gap between statistical theory and physical experiment, this is a thorough introduction to the statistical methods used in the experimental physical sciences and to the numerical methods used to implement them. An accompanying CD-ROM provides detailed code for implementing many of these algorithms. The treatment emphasises concise but rigorous mathematics but always retains its focus on applications. Readers are assumed to have a sound basic knowledge of differential and integral calculus and some knowledge of vectors and matrices. After an introduction to probability, random variables, computer generation of random numbers and important distributions, the book turns to statistical samples, the maximum likelihood method, and the testing of statistical hypotheses. The discussion concludes with several important statistical methods: least squares, analysis of variance, polynomial regression, and analysis of time series. Appendices provide the necessary methods of matrix algebra, combinatorics, and many sets of useful algorithms and formulae.

Antibodies tagged with fuorescent markers have been used in histochemistry for over 50 years. Although early applications were focused on the detection of microbial antigens in tissues, the use of immunocytochemical methods now has spread to include the det- tion of a wide array of antigens including proteins, carbohydrates, and lipids from virtually any organism. Today, immunohistochemistry is widely used to identify, in situ, various components of cells and tissues in both normal and pathological conditions. The method gains its strength from the extremely sensitive interaction of a specifc antibody with its antigen. For some scientifc areas, books have been published on applications of immu- cytochemical techniques specifc to that area. What distinguished Immunocytochemical Methods and Protocols from earlier books when it was frst published was its broad appeal to investigators across all disciplines, including those in both research and clinical settings. The methods and protocols p- sented in the frst edition were designed to be general in their application; the accompa- ing "Notes" provided the reader with invaluable assistance in adapting or troubleshooting the protocols. These strengths continued to hold true for the second edition and again for the third edition. Since the publication of the frst edition, the application of immuno- tochemical techniques in the clinical laboratory has continued to rise and this third edition provides methods that are applicable to basic research as well as to the clinical laboratory.

The synthesis of proteins from 20 or so constituent amino acids according to a strictly defined code with an accuracy of better than 1 in 10,000 at most loca tions is arguably the most complex task performed by cells. Protein Synthesis collects together methods and protocols covering a range of different approaches towards understanding how the cellular machinery accomplishes this task and how these ftinctions might be harnessed by the biotechnology industry to generate novel and useful proteins. The era in which the components of the translational machinery were being catalogued is over. This volume gathers together protocols that focus on preserving and describing the dynamic function as closely as possible. The need to understand exactly how ribosomes are positioned on messages or where tRNA molecules, translation factors, or control proteins are bound, has been appreciated by many of the authors. Several chapters that explore the fidelity and processivity of translation reflect this belief. Moreover, the fundamental importance of rRNA at the heart of the ribosome is a strong theme in a number of the protocols. These articles include in vitro and in vivo systems from bacterial, fungal, plant, and animal systems. Overall, Protein Synthesis might be characterized by the novelty of the approaches employed to illuminate the inner workings of the protein synthetic machinery as well as by the inventiveness of the attempts to harness these reactions for biotechnological applications."

With its focus on the practical application of the techniques of multivariate statistics, this book shapes the powerful tools of statistics for the specific needs of ecologists and makes statistics more applicable to their course of study. It gives readers a solid conceptual understanding of the role of multivariate statistics in ecological applications and the relationships among various techniques, while avoiding detailed mathematics and the underlying theory. More importantly, the reader will gain insight into the type of research questions best handled by each technique and the important considerations in applying them. Whether used as a textbook for specialised courses or as a supplement to general statistics texts, the book emphasises those techniques that students of ecology and natural resources most need to understand and employ in their research. While targeted for upper-division and graduate students in wildlife biology, forestry, and ecology, and for professional wildlife scientists and natural resource managers, this book will also be valuable to researchers in any of the biological sciences.

The field of high performance computing achieved prominence through advances in electronic and integrated technologies beginning in the 1940s. Current times are very exciting and the years to come will witness a proliferation of the use of parallel and distributed systems. The scientific and engineering application domains have a key role in shaping future research and development activities in academia and industry, especially when the solution of large and complex problems must cope with harder and harder timing.
High Performance Scientific And Engineering Computing: Hardware/Software Support contains selected chapters on hardware/software support for high performance scientific and engineering computing from prestigious workshops in the fields such as PACT-SHPSEC, IPDPS-PDSECA and ICPP-HPSECA. This edited volume is basically divided into six main sections which include invited material from prominent researchers around the world. We believe all of these contributed chapters and topics not only provide novel ideas, new results and state-of-the-art techniques in this field, but also stimulate the future research activities in the area of high performance computing for science and engineering applications.
High Performance Scientific And Engineering Computing: Hardware/Software Support is designed for a professional audience, composed of researchers and practitioners in industry. This book is also suitable as a secondary text for graduate-level students in computer science and engineering.

A comprehensive tutorial for researchers and practitioners involved in surface science. The basics of the scanning probe microscopy techniques as well as material class-specific applications are thoroughly discussed. The book gives access to these methods for advanced students and allows researchers to apply these powerful atomic-resolution imaging techniques to new systems.

Ribonucleic acids are central to cellular and molecular processes and perform vital functions in both structural and functional roles. RNA molecules form the bridge between the stable genetic information contained within DNA and enzymes and proteins that carry out much of the metabolism within the cell. Many of the sites of protein synthesis, the ribosomes within the cell, are composed of these ribonucleic acids as are the tRNA molecules that deliver the amino acid building blocks to the ribosomes. Of all the RNA species, the nucleic acid intermediate, messenger RNA, is a desirable source of material to biologists, since this reflects much of, what ultimately, is translated into enzymes and proteins. In order to determine the qualitative and quantitative changes in mRNA expression, a vast number of molecular biological techniques have been developed. Key molecular methods that provide the means to initially isolate and analyze RNA molecules are the focus of this volume. In putting together this collection of protocols, we have tried to provide techniques that are most applicable and widely used. In particular, there are a number of iso- tion techniques included that have been developed, modified, or adapted to enable extraction from a variety of cell types, organisms, or subcellular organelles. Successful isolation of intact RNA is an essential starting point for any sub- quent analysis. This is why we have aimed to make this section comprehensive. The analysis of RNA is the focus of the following chapters.

Presents recent developments in theoretical and experimental research of nanophotonics Discusses properties and features of nanophotonic devices, e.g. scanning near-field optical microscopy, nanofi ber/nanowire based photonic devices Illustrates the most promising nanophotonic devices and instruments and their application Suits well for researchers and graduates in nanophotonics field Contents Scanning near-field optical microscopy Nanofibers/nanowires and their applications in photonic components and devices Micro/nano-optoelectronic devices based on photonic crystal

This book represents the compilation of papers presented at the second Atomic Force Microscopy/Scanning Tunneling Microscopy (AFM/STM) Symposium, held June 7 to 9, 1994, in Natick, Massachusetts, at Natick Research, Development and Engineering Center, now part ofU.S. Army Soldier Systems Command. As with the 1993 symposium, the 1994 symposium provided a forum where scientists with a common interest in AFM, STM, and other probe microscopies could interact with one another, exchange ideas and explore the possibilities for future collaborations and working relationships. In addition to the scheduled talks and poster sessions, there was an equipment exhibit featuring the newest state-of-the-art AFM/STM microscopes, other probe microscopes, imaging hardware and software, as well as the latest microscope-related and sample preparation accessories. These were all very favorably received by the meeting's attendees. Following opening remarks by Natick's Commander, Colonel Morris E. Price, Jr., and the Technical Director, Dr. Robert W. Lewis, the symposium began with the Keynote Address given by Dr. Michael F. Crommie from Boston University. The agenda was divided into four major sessions. The papers (and posters) presented at the symposium represented a broad spectrum of topics in atomic force microscopy, scanning tunneling microscopy, and other probe microscopies.

Aquaculture is rapidly becoming a major source of fish protein used to meet the nutritional needs of humans. As the aquaculture industry grows, exposure of farmed fish to environmental contaminants, and the need for chemical therapeutic agents for fish, will increase. This book is designed to bring together authorities worldwide on the regulation of environmental contaminants and food chemicals and researchers investigating the metabolism and disposition of foreign chemicals (xenobiotics) in fish species.

In modern scanning electron microscopy, sample surface preparation is of key importance, just as it is in transmission electron microscopy. With the procedures for sample surface preparation provided in the present book, the enormous potential of advanced scanning electron microscopes can be realized fully. This will take the reader to an entirely new level of scanning electron microscopy and finely-detailed images never seen before. Written for: Scientists, practitioners, academic libraries, graduate students

The book deals mainly with direct mass determination by means of a conventional balances. It covers the history of the balance from the beginnings in Egypt earlier than 3000 BC to recent developments. All balance types are described with emphasis on scientific balances. Methods of indirect mass determination, which are applied to very light objects like molecules and the basic particles of matter and celestial bodies, are included. As additional guidance, today's manufacturers are listed and the profile of important companies is reviewed. Several hundred photographs, reproductions and drawings show instruments and their uses. This book includes commercial weighing instruments for merchandise and raw materials in workshops as well as symbolic weighing in the ancient Egyptian's ceremony of 'Weighing of the Heart', the Greek fate balance, the Roman Justitia, Juno Moneta and Middle Ages scenes of the Last Judgement with Jesus or St. Michael and of modern balances. The photographs are selected from the slide-archives of the late Richard Vieweg (1896-1972) (former President of the Physikalisch-Technische Bundesanstalt, Braunschweig, Germany), of the late Hans R. Jenemann (1920-1966) (former head of the Analytical Laboratory of Schott & Gen., Mainz, Germany) and of his wife Irene (1933-2008) and of Erich Robens.

Toxicity Assessment Alternatives: Methods, Issues, Opportunities contains a broad array of critical surveys, contributed by active and respected investigators, describing their research and offering updates on toxicity assessment alternatives, directions determined by current and future grant programs, opportunities for mechanistically based test methods to detect endocrine disruptor activity, the use of alternatives in the Department of Defense hazard assessment initiatives, and the issues and opportunities for validation and regulatory acceptance. Several of these advances make use oftransgenic models that reduce the time and cost of carcinogenicity testing. Others use tissue cultures for the assessment of endocrine disrupting chemicals. Cultures of human epidermal keratinocytes are applicable as models for sulfur mustard lesions, and in vitro protein denaturation is used as a chemical test for assessing the ocular and dermal irritation potential of cosmetic prod ucts. Molecular modeling is applied to explaining chemical toxicity. Commercially developed assay systems have undergone extensive evaluation by their manufacturers. Some of these await external valida tion, and others await acceptance by North American and European regulatory agencies. Toxicity Assessment Alternatives: Methods, Issues, Opportunities provides information from members of the scientific and regulatory communities on what has been achieved and what has been accepted in alternatives to animal testing."

Transmission electron microscopy (TEM) is now recognized as a crucial tool in materials science. This book, authored by a team of expert Chinese and international authors, covers many aspects of modern electron microscopy, from the architecture of novel electron microscopes, advanced theories and techniques in TEM and sample preparation, to a variety of hands-on examples of TEM applications. Volume II illustrates the important role that TEM is playing in the development and characterization of advanced materials, including nanostructures, interfacial structures, defects, and macromolecular complexes.

Transmission electron microscopy (TEM) is now recognized as a crucial tool in materials science. This book, authored by a team of expert Chinese and international authors, covers many aspects of modern electron microscopy, from the architecture of novel electron microscopes, advanced theories and techniques in TEM and sample preparation, to a variety of hands-on examples of TEM applications. Volume I concentrates on the newly developed concepts and methods which are making TEM a powerful and indispensible tool in materials science.

In 1957 two young scientists, Matthew Meselson and Frank Stahl, produced a landmark experiment confirming that DNA replicates as predicted by the double helix structure Watson and Crick had recently proposed. It also gained immediate renown as a "most beautiful" experiment whose beauty was tied to its simplicity. Yet the investigative path that led to the experiment was anything but simple, Frederic L. Holmes shows in this masterful account of Meselson and Stahl's quest. This book vividly reconstructs the complex route that led to the Meselson-Stahl experiment and provides an inside view of day-to-day scientific research--its unpredictability, excitement, intellectual challenge, and serendipitous windfalls, as well as its frustrations, unexpected diversions away from original plans, and chronic uncertainty. Holmes uses research logs, experimental films, correspondence, and interviews with the participants to record the history of Meselson and Stahl's research, from their first thinking about the problem through the publication of their dramatic results. Holmes also reviews the scientific community's reception of the experiment, the experiment's influence on later investigations, and the reasons for its reputation as an exceptionally beautiful experiment.

Fluorescence microscopy images can be easily integrated into current video and computer image processing systems. People like visual observation; they like to watch a television or computer screen, and fluorescence techniques are thus becoming more and more popular. Since true in vivo experiments are simple to perform, samples can be directly seen and there is always the possibility of manipulating the samples during the experiments; it is an ideal technique for biology and medicine. Images are obtained by a classical (now called wide-field) fluorescence microscope, a confocal scanning microscope, upright or inverted, with epifluorescence or transmission. Computerized image processing may improve definition, and remove glare and scattered light signal. It also makes it possible to compute ratio images (ratio imaging both in excitation and in emission) or lifetime imaging. Image analysis programs may supply a great deal of additional data of various types, starting with calculations of the number of fluorescent objects, their shapes, brightness, etc. Fluorescence microscopy data may be complemented by classical measurement in the cuvette yr by flow cytometry.

2. High Temperature UHV-STM System 264 3. Hydrogen Desorption Process on Si (111) Surface 264 4. (7x7) - (1 xl) Phase Transition on Si (111) Surface 271 Step Shifting under dc Electric Fields 275 5. 6. Conclusions 280 Acknowledgements and References 281 12. DYNAMIC OBSERVATION OF VORTICES IN SUPERCONDUCTORS USING ELECTRON WAVES 283 by Akira Tonomura 1. Introduction 283 2. Experimental Method 284 2. 1 Interference Microscopy 284 2. 2 Lorentz Microscopy 287 Observation of Superconducting Vortices 288 3. 3. 1 Superconducting Vortices Observed by Interference Microscopy 288 3. 1. 1 Profile Mode 288 3. 1. 2 Transmission Mode 291 3. 2 Superconducting Vortices Observed by Lorentz Microscopy 293 3. 3 Observation of Vortex Interaction with Pinning Centers 294 3. 3. 1 Surface Steps 295 3. 3. 2 Irradiated Point Defects 296 4. Conclusion 298 References 299 13. TEM STUDIES OF SOME STRUCTURALLY FLEXIBLE SOLIDS AND THEIR ASSOCIATED PHASE TRANSFORMATIONS 301 by Ray L. Withers and John G. Thompson 1. Introduction 301 2. Tetrahedrally Comer-Connected Framework Structures 302 3. Tetragonal a-PbO 311 4. Compositionally Flexible Anion-Deficient Fluorites and the "Defect Fluorite" to C-type Sesquioxide Transition 320 5. Summary and Conclusions 327 Acknowledgements and References 327 Author Index 331 Subject Index 333 List of Contributors A. ASEEV Institute of Semiconductor Physics, Russian Academy of Sciences Novosibirsk, 630090, pr. ac. , Lavrentjeva 13, RUSSIA E. BAUER Department of Physics and Astronomy, Arizona State University Tempe, AZ 85287-1504, U. S. A. G. H.

The purpose of Ribozyme Protocols is to provide a helpful compilation of protocols that will be of use- DEGREESnot only to those with some experience of ribozymes- DEGREESbut also to those wishing to use ribozymes for the first time. Although it is usually impossible to cover every aspect of a scientific field, I believe this book approaches that ideal and should help all readers perform meaningful experiments using ribozymes. To design ribozymes, one must consider whether the target site will be accessible; this task can be facilitated by using computer programs that pre dict the folding of the target RNA. Such programs are detailed in Chapters 2 and 3. If the chosen target is an RNA virus that can mutate rapidly, it makes sense to consider those parts of the genome that are least likely to change during viral replication. An example of how this can be done is described in Chapter 4. Although computer analysis may be a useful starting point to select tar get sites, there seems, at the moment, to be no guarantee that any particular chosen site will be efficiently cleaved. Some workers have deliberately bypassed this problem by using libraries of ribozyme sequences and by select ing those that actually hybridize to and/or cleave the target; these methods are described in Chapters 5

This book is focused on the current status of industrial pollution, its source, characteristics, and management through various advanced treatment technologies. The book covers the recycle, reuse and recovery of waste for the production of value-added products. The book explores industrial wastewater pollution and its treatment through various advanced technologies and also the source and characteristics of solid waste and its management for environmental safety. It discusses new methods and technologies to combat the waste-related pollution and focuses on the use of recycled products. This book is of value to upcoming students, researchers, scientists, industry persons and professionals in the field of environmental science and engineering, microbiology, biotechnology, toxicology, further it is useful for global and local authorities and policy makers responsible for the management of liquid and solid wastes.

Determination of the protein sequence is as important today as it was a half century ago, even though the techniques and purposes have changed over time. Mass spectrometry has continued its recent rapid development to find notable application in the characterization of small amounts of protein, for example, in the field of proteomics. The "traditional" chemical N-terminal sequencing is still of great value in quality assurance of the increasing number of biopharmaceuticals that are to be found in the clinic, checking processing events of recombinant proteins, and so on. It is joined in the armory of me- ods of protein analysis by such techniques as C-terminal sequencing and amino acid analysis. These methods are continually developing. The first edition of Protein Sequencing Protocols was a "snapshot" of methods in use in protein biochemistry laboratories at the time, and this, the second edition, is likewise. Methods have evolved in the intervening period, and the content of this book has similarly changed, the content of some chapters having been superceded and replaced by other approaches. Thus, in this edition, there is inclusion of approaches to validation of methods for quality assurance work, reflecting the current importance of biopharmaceuticals, and also a guide to further analysis of protein sequence information, acknowledging the importance of bioinformatics.