This book covers the principles of cryopreservation as they relate the preservation of viable cells and cell materials being developed for biopharmaceutical applications. Topics include: the principles of freezing and thawing cells, physiochemical phenomena, process and system design options, method selection considerations, preservation procedures, cryoprotectant additives, freeze-drying human live virus vaccines, and transport system selection criteria. Contributions from well-known experts such as Steven S. Lee, Thomas C. Pringle, William H. Siegel, Richard Wisniewski, and Fangdong Yin make this the single most important study available.

'A most moving and important biography, as well as an impressive account of a major event in the history of science'
Lewis Wolpert, 'Literary Review'

Although Rosalind Franklin took the crucial photograph of DNA revealing its double helix structure, her work was overlooked when, four years after her death, three men – Maurice Wilkins of King's College London, Francis Crick of the Cavendish Laboratory and James Watson of Cambridge – were awarded the Nobel Prize for the discovery of DNA.

In this compelling biography of Franklin, Brenda Maddox tells the story of a remarkably single-minded, forthright and tempestuous young woman, who at the age of fifteen decided she wanted to be a scientist, but who was airbrushed out of the greatest scientific discovery of the twentieth century.

'Maddox is a dab hand at drawing a heroine out from behind the long shadows cast by men and her Franklin emerges as a determined, combative woman – a perfectionist who is plagued with self doubt'
Vanessa Thorpe, 'Observer'

'This magnificent biography gives a gripping yet nuanced account that resists the stock story-line of Franklin as the wronged heroine. What really happened is far more intriguing.'
Gail Vines, 'Independent'

'An exhilarating and vivid tale of scientific and personal politics at a time of rapid change in British science.'
Jane Gregory, 'New Scientist'

New Findings Revolutionize Concepts of Gene Function

Endogenous small RNAs have been found in various organisms, including humans, mice, flies, worms, fungi, and bacteria. Furthermore, it 's been shown that microRNAs acting as cellular rheostats have the ability to modulate gene expression. In higher eukaryotes, microRNAs may regulate as much as 50 percent of gene expression.

Regulation of Gene Expression by Small RNAs brings together the pioneering work of researchers who discuss their work involving a wide variety of small RNA regulatory pathways in organisms ranging from bacteria to humans. In addition to exploring the biogenesis and processing of these regulatory RNAs, they also consider the functional importance of these pathways in host organisms. Assisting current and future researchers, this unique groundbreaking work

• Provides a suite of cutting-edge resources for the study of microRNA ontology and function
• Includes a technology guide for those seeking to assay microRNA expression
• Explores the mechanisms by which microRNAs regulate gene expression in animal cells, including the regulation of gene expression by RNA-mediated transcriptional gene silencing
• Discusses a fast and low-cost approach for reversing genetic influences in mammals
• Looks at breakthroughs in the use of microRNA-based therapy for HIV and cancer

This volume captures the essence of the breadth and excitement surrounding the newly discovered regulatory roles of small RNAs. The powerful new approach in the study of gene function described in this text is leading to some remarkable findings that have the potential to revolutionize our understanding of genetic function and the treatment of diseases otherwise considered intractable.

This book constitutes the refereed proceedings of the 5th RECOMB Comparative Genomics Satellite Workshop, RECOMB-CG 2007, held in San Diego, CA, USA, in September 2007.

The 14 revised full papers presented were carefully reviewed and selected from 18 initial submissions. The papers address a broad variety of aspects and components of the field of comparative genomics, ranging from quantitative discoveries about genome structure to algorithms for comparative inference to theorems on the complexity of computational problems required for genome comparison.

The massive research effort known as the Human Genome Project is an attempt to record the sequence of the three trillion nucleotides that make up the human genome and to identify individual genes within this sequence. The description and classification of sequences is heavily dependent on mathematical and statistical models. This short textbook presents a brief description of several ways in which mathematics and statistics are being used in genome analysis and sequencing.

This book provides an exceptionally friendly introduction to Perl that emphasizes good programming practices with repeated exposure to pattern matching as applied to biological sequence analysis (DNA analysis, Protein analysis). The full-length book is appropriate for postgraduates in either computer science or biology and especially relevant to new interdisciplinary courses involving students from multiple disciplines.

This book presents Perl programming with a uniquely interdisciplinary perspective for the bioinformatics classroom. The co-authors are a professor of computer science and a professor of biology who collaborate in developing software for DNA sequence analysis. A specialty of the authors is encouraging interdisciplinary undergraduate research. The book has been tested in the classroom as a text for both biology and computer science majors. Benefiting from years of teaching experience in both computer science and biology, the authors use an exceptionally friendly and pedagogically sound introduction to Perl that emphasizes good programming practices throughout. Concepts include a rich introduction to working with strings and files of sequence data, control structures, subroutines, and data structures (e.g., arrays and hash tables). A particularly unique feature of the text is the early and repeated exposure to and use of regular expressions in sequence analysis. All examples in the book are applied to biological sequence analysis (DNA analysis, Protein analysis). The full-length book is appropriate for majors in either computer science or biology and especially relevant for new interdisciplinary courses involving students from multiple disciplines.

This book constitutes the refereed proceedings of the 4th RECOMB Comparative Genomics Satellite Workshop, RECOMB-CG 2006. The 17 revised full papers presented were carefully reviewed and selected from 34 initial submissions. The papers address a broad variety of aspects and components of the field of comparative genomics, ranging from new quantitative discoveries about genome structure and process to theorems on the complexity of computational problems inspired by genome comparison.

In its short but active history, the use of DNA typing has revolutionized criminal investigations. It is almost inconceivable to bring a case to trial without positive identification through what is now our most accurate means. Proficiency with the methodology, principles, and interpretation of DNA evidence is crucial for today's criminalist. An introductory text, Forensic DNA Analysis: A Laboratory Manual presents a contextual history and overview of the science and use of DNA typing. Logically organized, with clear, concise language, this manual provides a fundamental understanding of forensic DNA analysis and a thorough background in the molecular techniques used to determine an individual's identity. Students are provided with a sound working knowledge of the investigative methodology, scientific principles, and the analysis and interpretation of the resulting data. After laying a foundation on the rules of the laboratory, the basic scientific principles, and the types of biological materials, such as hair, blood, and bone, this practical, hands-on manual provides 12 exercises outlining techniques commonly used in DNA typing. Designed to be performed in a common laboratory, the experiments cover DNA extraction, concentration, and assessment; DNA analysis using restriction fragment length polymorphisms; polymerase chain reaction and PCR-based typing tests; short tandem repeat analysis; and mitochondrial DNA analysis. Many of the procedures described have been adapted from methods used in federal, state, and private forensic laboratories and are suitable to a wide range of applications. There is also an extensive glossary for DNA typing terminology and basic terms used in molecular biology. Instilling confidence, analytical clarity, and a sense of curiosity, this comprehensive introduction is the perfect tool for grasping the techniques and applications of forensic DNA analysis and exploring the questions and issues involved in forensic science investigations.

This book is about the increasing significance of DNA profiling for crime investigation in modern society. It focuses on developments in the UK as the world-leader in the development and application of forensic DNA technology and in the construction of DNA databases as an essential element in the successful use of DNA for forensic purposes. The book uses data collected during the course of Wellcome Trust funded research into police uses of the UK National DNA Database (NDNAD) to describe the relationship between scientific knowledge and police investigations. It will be illustrated throughout by reference to some of the major UK criminal cases in which DNA evidence has been presented and contested. Chapters in the book explain the scientific developments which have enabled DNA profiling to be applied to criminal investigation, the ways in which the state has directed this and how genetic technology has risen to such preeminence; how DNA evidence moved from its use in individual prosecutions to a major role in intelligence led policing, and saw the development of the UK National DNA Database; how legislative support for the NDNAD was mobilized, enabling the police to obtain and use genetic information on individuals. Finally, the authors examine the ways in which the DNA Expansion Programme, built on the supposed potential for the NDNAD to contribute to criminal detection, has been incorporated into a broader crime reduction strategy, and explore the implications for policing, governance and security of the continued expansion of the range and scope of the NDNAD.

The complexity of genome evolution poses many exciting challenges to devel- ers of mathematical models and algorithms, who have recourse to a spectrum of algorithmic, statisticalandmathematicaltechniques, rangingfromexact, heur- tic, ?xed-parameter and approximation algorithms for problems based on par- mony models to Monte Carlo Markov Chain algorithms for Bayesian analysis of problems based on probabilistic models. The annual RECOMB Satellite Workshop on Comparative Genomics (RECOMB ComparativeGenomics)is aforumonallaspects andcomponents of this ?eld, rangingfromnew quantitativediscoveriesabout genomestructureand process to theorems on the complexity of computational problems inspired by genome comparison. The informal steering committee for this meeting consists of David Sanko?, Jens Lagergren and Aoife McLysaght. Thisvolumecontainsthepaperspresentedatthe3rdRECOMBComparative Genomicsmeeting, whichwasheldinDublin, Ireland, onSeptember18-20,2005. The ?rst two meetings of this series were held in Minneapolis, USA (2003) and Bertinoro, Italy (2004). This year, 21 papers were submitted, of which the Program Committee - lected 14 for presentation at the meeting and inclusion in this proceedings.Each submission was refereed by at least three members of the Program Committee. Aftercompletionofthereferees'reports, anextensiveWeb-baseddiscussiontook placeformakingdecisions.TheRECOMBComparativeGenomics2005Program Committee consisted of the following 27 members: Vineet Bafna, Anne Be- eron, Mathieu Blanchette, Avril Coghlan, Dannie Durand, Nadia El-Mabrouk, Niklas Eriksen, Aaron Halpern, Rose Hoberman, Daniel Huson, Jens Lagergren, Giuseppe Lancia, Emmanuelle Lerat, Aoife McLysaght, Istvan Miklos, Bernard Moret, PavelPevzner, Ben Raphael, Marie-FranceSagot, David Sanko?, Cathal Seoighe, Beth Shapiro, Igor Sharakhov, Mike Steel, Jens Stoye, Glenn Tesler and Louxin Zhan. We would like to thank the ProgramCommittee members for their dedication and hard wo

Research in the ?eld of gene regulation is evolving rapidly in an ever-changing s- enti?c environment. Microarray techniques and comparative genomics have enabled more comprehensive studies of regulatory genomics and are proving to be powerful tools of discovery. The application of chromatin immunoprecipitation and microarrays (chIP-on-chip) to directly study the genomic binding locations of transcription factors has enabled more comprehensive modeling of regulatory networks. In addition, c- plete genome sequences and the comparison of numerous related species has dem- strated that conservation in non-coding DNA sequences often provides evidence for cis-regulatory binding sites. That said, much is still to be learned about the regulatory networks of these sequenced genomes. Systematic methods to decipher the regulatory mechanism are also crucial for c- roboratingthese regulatorynetworks.Thecoreof thesemethodsarethe motifdiscovery algorithms that can help predict cis-regulatory elements. These DNA-motif discovery programsarebecomingmoresophisticatedandare beginningto leverageevidencefrom comparative genomics (phylogenetic footprinting) and chIP-on-chip studies. How to use these new sources of evidence is an active area of research.

For over half a century, we have been in the thrall of the double-helicaln structure of DNA, which, in an instant, revealed that information can be transferred between generations by a simple rule, A pairs with T, G pairs with C. In its beautiful simplicity, this structure, along with the table of codons worked out in the following decade, had entranced us into believing that we can fully understand the information content of a DNA sequence, simply by treating it as text that is read in a linear fashion. While we have learned much based on this assumption, there is much we have missed. Far from a passive tape running through a reader, genomes contain information that appears in new forms which create regions with distinct behavior. Some are "gene rich," some mobile, some full of repeats and duplications, some sticking together across long evolutionary distances, some readily breaking apart in tumor cells. Even protein-coding regions can carry additional information, taking advantage of the flexible coding options provided by the degeneracy of the genetic code. The chapters in this volume touch on one or more of three interconnected themes; information can be implied, rather than explicit, in a genome; information can lead to focused and/or regulated changes in nucleotide sequences; information that affects the probability of distinct classes of mutation has implications for evolutionary theory.

Flow cytometry is a sensitive and quantitative platform for the measurement of particle fluorescence. In flow cytometry, the particles in a sample flow in single file through a focused laser beam at rates of hundreds to thousands of particles per second. During the time each particle is in the laser beam, on the order of ten microseconds, one or more fluorescent dyes associated with that particle are excited. The fluorescence emitted from each particle is collected through a microscope objective, spectrally filtered, and detected with photomultiplier tubes.
Flow cytometry is uniquely capable of the precise and quantitative molecular analysis of genomic sequence information, interactions between purified biomolecules and cellular function. Combined with automated sample handling for increased sample throughput, these features make flow cytometry a versatile platform with applications at many stages of drug discovery. Traditionally, the particles studied are cells, especially blood cells; flow cytometry is used extensively in immunology.
This volume shows how flow cytometry is integrated into modern biotechnology, dealing with issues of throughput, content, sensitivity, and high throughput informatics with applications in genomics, proteomics and protein-protein interactions, drug discovery, vaccine development, plant and reproductive biology, pharmacology and toxicology, cell-cell interactions and protein engineering.

DNA as the genetic material is a topic of intense interest in the 21st century with the familiar and iconic Watson-Crick double helix having a vital importance for its function. However, there are further complexities beyond the double helix, including supercoiling, knotting and catenation, that are less widely appreciated and understood but which are critical to its function. This book explains these topological aspects of DNA structure in a clear and approachable style that will be appreciated by both students and researchers interested in DNA structure and function.

Crick and Watson's discovery of the structure of DNA fifty years ago marked one of the great turning points in the history of science. Biology, immunology, medicine and genetics have all been radically transformed in the succeeding half-century, and the double helix has become an icon of our times. This fascinating exploration of a scientific phenomenon provides a lucid and engaging account of the background and context for the discovery, its significance and afterlife, while a series of essays by leading scientists, historians and commentators offers uniquely individual perspectives on DNA and its impact on modern science and society.

This volume describes high-throughput approaches to a series of robust, established methodologies in molecular genetic studies of population samples. Such developments have been essential not only to linkage and association studies of single-gene and complex traits in humans, animals and plants, but also to the characterisation of clone banks, for example in mapping of genomes. Chapters have been written by developers or highly experienced end-users concerned with a diverse array of biological applications. The book should appeal to any researcher for whom costs and throughput in their genetics laboratory have become an issue.

A comprehensive account of genomic rearrangement, focusing on the mechanisms of inversion, translocation, gene and genome duplication and gene transfer and on the patterns that result from them in comparative maps. Includes analyses of genomic sequences in organelles, prokaryotes and eukaryotes as well as comparative maps of the nuclear genomes in higher plants and animals. The book showcases a variety of algorithmic and statistical approaches to rearrangement and map data.

This complete and practical manual on expression measurement using DNA arrays covers the existing methods (from nylon macroarrays to oligonucleotide chips) and includes detailed protocols. It has been written by practising scientists who have experienced the difficulties involved in actually using microarrays, and provides helpful advice and hints on setting up these powerful but sometimes tricky methods. Software, data mining procedures and probable future developments, which should be useful to any practising scientist interested in expression measurement, are also covered in this book. It also provides detailed protocols as well as many helpful hints to achieve experimental success and to avoid pitfalls.

Colin Graham and a team of leading investigators and expert clinical scientists update the acclaimed first edition with a collection of powerful, up-to-date PCR-based methods for DNA sequencing, many suitable for human genome sequencing and mutation detection in human disease. This second edition offers new material on automated DNA sequencers, capillary DNA sequencers, heterozygote mutation detection, web-based sequencing databases and genome sequencing sites, and the human genome project. State-of-the-art and highly practical, DNA Sequencing Protocols, 2nd Edn. constitutes an essential laboratory handbook for geneticists and molecular biologists, offering concise, easy-to-follow methods that will work and impact today's genome sequencing projects.

Biomedical research will be revolutionised by the current efforts to sequence the human genome and the genomes of model organisms. Of the newly sequenced genes, 50% code for proteins of unknown functions, while as little as 5% of sequences in mammalian genomes code for proteins. New, genome-wide approaches are needed to draw together the knowledge that is emerging simultaneously in a number of fields of genome research. This volume is a high-level survey of the newly emerging concepts of structural biology and functional genomics for biologists, biochemists and medical researchers interested in genome research. Topics included are chromosome and chromatin organisation, novel DNA and RNA structures, DNA flexibility, supercoiling, prediction of protein functions, strategies for large scale structural analysis, and computer modelling.

The field of eukaryotic DNA repair is enjoying a period of remarkable growth and discovery, fueled by technological advances in molecular biol- ogy, protein biochemistry, and genetics. Notahle achievements include the molecular cloning of multiple genes associated with classical human repair disorders, such as xeroderma pigmentosum, Cockayne syndrome, and ataxia telangiectasia; elucidation of the core reaction of nucleotide excision repair (NER); the discovery that certain NER proteins participate not only in repair, but also in transcription; recognition of the crucial role played by mismatch repair processes in maintenance of genome stability and avoidance of cancer; the findings that the tumor suppressor protein p53 is mutated in many types of cancer, and has a key role in directing potentially malignant, genotoxin-dam- aged cells towards an apoptotic fate; and the discovery and elaboration of DNA darnage (and replication) checkpoints, which placed repair phenomenol- ogy firmly within a cell-cycle context. Of course, much remains to be learned about DNA repair. Tothat end, DNA Repair Protocols: Eukaryotic Systems is about the tools and techniques that have helped propel the DNA repair field into the mainstream of biological research. DNA Repair Protoco/s: Eukaryotic Systems provides detailed, step-by- step instructions for studying manifold aspects of the eukaryotic response to genomic injury. The majority of chapters describe methods for analyzing DNA repair processes in mammalian cells. However, many ofthose techniques can be applied with only minor modification to other systems, and vice versa.

This book provides a timely summary of physical modeling approaches applied to biological datasets that describe conformational properties of chromosomes in the cell nucleus. Chapters explain how to convert raw experimental data into 3D conformations, and how to use models to better understand biophysical mechanisms that control chromosome conformation. The coverage ranges from introductory chapters to modeling aspects related to polymer physics, and data-driven models for genomic domains, the entire human genome, epigenome folding, chromosome structure and dynamics, and predicting 3D genome structure.

Life's Greatest Secret is the story of the discovery and cracking of the genetic code. This great scientific breakthrough has had far-reaching consequences for how we understand ourselves and our place in the natural world. The code forms the most striking proof of Darwin's hypothesis that all organisms are related, holds tremendous promise for improving human well-being, and has transformed the way we think about life. Matthew Cobb interweaves science, biography and anecdote in a book that mixes remarkable insights, theoretical dead-ends and ingenious experiments with the pace of a thriller. He describes cooperation and competition among some of the twentieth century's most outstanding and eccentric minds, moves between biology, physics and chemistry, and shows the part played by computing and cybernetics. The story spans the globe, from Cambridge MA to Cambridge UK, New York to Paris, London to Moscow. It is both thrilling science and a fascinating story about how science is done.

In Managing Health in the Genomic Era: A Guide to Family Health History and Disease Risk, Drs. Vincent C. Henrich, Lori A. Orlando, and Brian H. Shirts discuss the practical considerations surrounding the use of genomic and genetic tests to manage patient health, to provide adult disease risk assessment, to improve diagnosis, and to support effective interventions and treatment. In 10 chapters, evidence-based information and case studies are described and examine the central place of family health history (FHH) in genomic medicine, tools and strategies for compiling and analyzing family health history, how to identify existing and novel genetic markers, how to identify lineage specific (or rare) variants within families, and how to find effective interventions based on genetic testing results and FHH. Factors that influence clinical practice, including gene-environment interactions, FHH social networking, direct to consumer (DTC) genetic testing and data sharing, algorithms for analyzing genetic data, and patient counseling are discussed from the standpoint of clinical practice. Here, frontline healthcare providers will discover succinct commentary and key examples to assist with their local needs. Relevant principles of genetic biology and inheritance are explored and guidance on available support networks and online resources is also provided.