Target Discovery and Validation: Reviews and Protocols, Volumes 1 and 2 review the most progressive and current methods for drug target discovery and validation. These volumes explore how recent improvement in understanding the molecular mechanisms of human pathology is impacting drug target discovery in the laboratory and in real therapeutics, specifically for cancers and autoimmune disorders.
Volume 1 focuses on novel and innovative techniques, and presents the most up-to-date protocols available for maximizing the likelihood of achieving target-selective inhibition in vivo while minimizing side effects. The profound impact of genomics, proteomics and bioinformatics on target discovery is explored, and specific attention is given to the role of transgenic and knockout animals in functional genomics and target validation. Cancer researchers will find tremendous value in the molecular classification of breast cancers and the review of protocols for tumor antigens and cancer vaccines. The methods and protocols collected here, all reviewed by leading scientists and clinicians, present the practical details necessary for translating the enormous discovery potential of the genome into real therapeutic products.
Volume 2 collects all the practical details required for efficient translation of discovered targets into real pharmaceutical drugs. Specific targets in cancers and autoimmunity are described and the potential of using siRNA's, antisense oligonucleotides and RNA aptimers in patients is reviewed. This volume explores the tremendous impact of the application of genotyping and gene expression profiling on the future of healthcare, and presents cutting-edge protocols to aid inbringing agents against specific targets closer to application in the clinic.
Collectively, these volumes provide a thorough review of the most cutting-edge methods available for each step in drug target identification, validation, and clinical application. For researchers, an understanding of available methods aids in the creation of innovative experiments in the laboratory, and the successful translation of target discovery to real therapeutics.

This detailed book arrives as there is an increasing need for multiplex biomarker readouts for improved clinical management and to support the development of new drugs by pharmaceutical companies, due to continuous technical developments and new insights into the high complexity of many diseases. Chapters explore the basic technology platforms being applied in the fields of genomics, proteomics, transcriptomics, metabolomics, and imaging, which are currently the methods of choice in multiplex biomarker research. The book also describes the chief medical areas in which the greatest progress has been made and highlight areas where further resources are required. Written for the highly successful Methods in Molecular Biology series, methodology chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Multiplex Biomarker Techniques: Methods and Applications serves as an ideal resource for a wide variety of researchers interested in these vital multiplex techniques.

Scholarpedia's Encyclopedia of Touch provides a comprehensive collection of peer-reviewed articles written by leading researchers, detailing our current scientific understanding of tactile sensing and its neural substrates in animals including humans. The encyclopedia allows ideas and insights to be shared between researchers working on different aspects of touch and in different species, including research in synthetic touch systems. In addition, this encyclopedia raises awareness of research in tactile sensing and increases scientific and public interest in the field. The articles address subjects including tactile control, whiskered robots, vibrissal coding, the molecular basis of touch, invertebrate mechanoreception, fingertip transducers and tactile sensing. All the articles in this encyclopedia provide in-depth and state-of-the-art scholarly treatment of the academic topics concerned, making it an excellent reference work for academics, professionals and students.

Since the beginning of agricultural production, there has been a continuous effort to grow more and better quality food to feed ever increasing popula tions. Both improved cultural practices and improved crop plants have al lowed us to divert more human resources to non-agricultural activities while still increasing agricultural production. Malthusian population predictions continue to alarm agricultural researchers, especially plant breeders, to seek new technologies that will continue to allow us to produce more and better food by fewer people on less land. Both improvement of existing cultivars and development of new high-yielding cultivars are common goals for breeders of all crops. In vitro haploid production is among the new technologies that show great promise toward the goal of increasing crop yields by making similar germplasm available for many crops that was used to implement one of the greatest plant breeding success stories of this century, i. e., the development of hybrid maize by crosses of inbred lines. One of the main applications of anther culture has been to produce diploid homozygous pure lines in a single generation, thus saving many generations of backcrossing to reach homozygosity by traditional means or in crops where self-pollination is not possible. Because doubled haploids are equivalent to inbred lines, their value has been appreciated by plant breeders for decades. The search for natural haploids and methods to induce them has been ongoing since the beginning of the 20th century."

The series "Advances in Dendritic Macromolecules" aims to cover the synthetic, as well as chemical, aspects of this expanding field: the chemistry to and supramolecular chemistry of dendritic or cascade supermolecular compounds. In Chapter 1 of this volume, Hawker and Wooley delineate the convergent growth approach to dendrimers, then relate their three-dimensional architectures to different block polymers. In Chapter 2, Moors and Vogtle describe Professor Vogtle's initial cascade molecules via the repetitive strategy, then expand his original concepts of its application by others, and lastly delineate the synthesis of a new series of tosylamide cascades. They also demonstrate the utility of his original Michael addition/reduction procedure by its application to differ cores. Chapter 3, composed by Professor Engel, describes ionic dendrimers which incorporated an internal transition metal center as well as his work based on ammonium and phosphonium centers. In Chapter 4, Mathias and Carothers review recent studies on silicon-based dendrimers and hyperbranched polymers. Chapter 5, by Kim, describes the preparation and utility of hyperbranched aromatic polymers. Lastly in Chapter 6, Escamilla reviews the historical as well as recent examples of ionic and nonionic bolaamphiphiles.

This book provides insights into the genetics and the latest advances in genomics research on the common bean, offering a timely overview of topics that are pertinent for future developments in legume genomics. The common bean (Phaseolus vulgaris L.) is the most important grain legume crop for food consumption worldwide, as well as a model for legume research, and the availability of the genome sequence has completely changed the paradigm of the ongoing research on the species. Key topics covered include the numerous genetic and genomic resources, available tools, the identified genes and quantitative trait locus (QTL) identified, and there is a particular emphasis on domestication. It is a valuable resource for students and researchers interested in the genetics and genomics of the common bean and legumes in general.

The technique of in situ hybridization is now vital to molecular biologists and their understanding of the pathophysiology of cellular functions. This practical guide covers all aspects of in situ hybridization, describing: practical procedures and protocols; the scientific background; areas of application; and the limitations of the technology. This edition has been completely rewritten to take into acocunt the many advances in the seven years since its initial publication.

The 18 chapters making up In Vitro Haploid Production in Higher Plants are divided into two sections. Section 1 (eight chapters) covers historical and fundamental aspects of haploidy in crop improvement. Section 2 deals with methods of haploid production, including anther culture, micropore culture, ovary culture, pollination with irradiated pollen, in vitro pollination, and special culture techniques, including polyhaploid production in the Triticeae by sexual hybridization, the influence of ethylene and gelling agents on anther culture, conditional lethal markers, and methods of chromosome doubling.

From the pre-historic era to modern times, cereal grains have been the most important source of human nutrition, and have helped sustain the increasing population and the development of human civilization. In order to meet the food needs of the 21st century, food production must be doubled by the year 2025, and nearly tripled by 2050. Such enormous increases in food productivity cannot be brought about by relying entirely on conventional breeding methods, especially on less land per capita, with poor quality and quantity of water, and under rapidly deteriorating environmental conditions. Complementing and supplementing the breeding of major food crops, such as the cereals, which together account for 66% of the world food supply, with molecular breeding and genetic manipulation may well provide a grace period of about 50 years in which to control population growth and achieve sustainable development. In this volume, leading world experts on cereal biotechnology describe the production and commercialization of the first generation of transgenic cereals designed to substantially reduce or prevent the enormous losses to cereal productivity caused by competition with weeds, and by various pests and pathogens, which is an important first step in that direction.

In Neuroprotective Signal Transduction prominent researchers and clinicians focus on how inter- and intracellular signaling mechanisms prevent the degeneration and death of neurons occurring in both acute and chronic neurodegenerative disorders. Authoritative contributions dissect the signaling pathways of an array of neuroprotective factors-ranging from neurotrophins (NGF, BDNF, NT-3, and NT-4/5), to growth factors (bFGF, IGF-1, GDNF), to cytokines (TNF, IL-1b, and TGFb), to secreted amyloid precursor proteins, to protease nexin-1. Also treated are cytoprotective signaling events that occur within injured neurons independently of intercellular signals. Neuroprotective Signal Transduction presents fundamental, cutting-edge treatment of the cellular and molecular signal transduction pathways found in human neurodegenerative conditions. The book's elucidation of the molecular cascades evolved by the nervous system to protect itself is now lead to effective strategies for preventing neuronal degeneration in such conditions as stroke, traumatic brain injury, Alzheimer's disease, Parkinson's disease, Huntington's disease, and amyotrophic lateral sclerosis, and will form the basis for powerful new drug discovery and gene therapy strategies.

When first conceived, not only was the aim of Protocols for Oligo nucleotides and Analogs to provide wide coverage of the ohgonuc- otide chemistry field for readers who are well versed within the field, but also to give investigators just entering into the field a new perspective. The very first book on this topic was edited and published by Michael Gait in 1984, in whose laboratory I encountered the newer aspects of oligonucleotide chemistry. Since then, oligonucleotide research has developed to such an extent that its uses extend far beyond basic studies, and now find wide application throughout clinical science as well. Until recently, the major application of oligonucleotides has been in the area of DNA-based diagnostic and "antisense oligonucleotid- based therapeutic approaches. However, oligonucleotides are now also being used as therapeutic agents and are thus frequently found in clinical trials in humans. Synthesis of unmodified oligonucleotides using automated synthe sizers has become a common practice in numerous laboratories. How ever, improvements on the existing techniques and the introduction of ever newer methods for oligonucleotide synthesis is constantly driving ahead in the leading research laboratories. And several new oligonucle otide analogs have been synthesized and studied for their individual prop erties in recent years. The present volume strives to bring the readers the most up-to-date information on the newest aspects of synthesis of oligo nucleotides and their analogs. A separate volume covers synthesis of oligonucleotide conjugates, along with most of the analytical techniques presently used for analysis of oligonucleotides."

The Chlamydomonas Sourcebook, Third Edition, Volume Two: Organellar and Metabolic Processes has been fully revised and updated to include a wealth of new resources for the Chlamydomonas community. Long known for its comprehensive insights into this highly multidisciplinary topic, this edition includes new views on Chlamydomonas branched electron transfer pathways in photosynthesis, the organization of pyrenoids and CO2 concentration mechanisms, and the fermentative-aspects of dark metabolism. Further, the book covers Chlamydomonas and its use in microalgae biotechnology. In addition to updates to previous editions, this book presents the latest in research and best practices, thus making it a must-have resource for those working with the Chlamydomonas organism.

The Chlamydomonas Sourcebook, Third Edition, Volume Three: Cell Motility and Behavior has been fully revised and updated to include the wealth of new resources for the Chlamydomonas community. The book presents the latest advances in the area from an international array of expert authors, reflecting significant advancements in our understanding of the role of basal bodies and flagella in human diseases. In addition, employing quantitative proteomics/mass spectroscopy as well as cryo EM tomography and single particle cryo EM has revolutionized our knowledge of the axoneme in terms of the location of proteins and their interactions. Current insights on mitosis and cytokinesis, flagellar assembly and motility, intraflagellar transport, and more will ensure use of this reference as a guide for understanding human diseases of the cilium.

This book is the third revised and updated English edition of the German textbook \Versuchsplanung und Modellwahl" by Helge Toutenburg which was based on more than 15 years experience of lectures on the course \- sign of Experiments" at the University of Munich and interactions with the statisticians from industries and other areas of applied sciences and en- neering. This is a type of resource/ reference book which contains statistical methods used by researchers in applied areas. Because of the diverse ex- ples combined with software demonstrations it is also useful as a textbook in more advanced courses, The applications of design of experiments have seen a signi?cant growth in the last few decades in di?erent areas like industries, pharmaceutical sciences, medical sciences, engineering sciences etc. The second edition of this book received appreciation from academicians, teachers, students and applied statisticians. As a consequence, Springer-Verlag invited Helge Toutenburg to revise it and he invited Shalabh for the third edition of the book. In our experience with students, statisticians from industries and - searchers from other ?elds of experimental sciences, we realized the importance of several topics in the design of experiments which will - crease the utility of this book. Moreover we experienced that these topics are mostly explained only theoretically in most of the available books.

In 1992 a Concerted Action Programme (CAP) was initiated by Peter Sijmons with the purpose of intensifying collaborations between 16 European laboratories working on plant-parasitic nematodes. The four-year programme entitled "Resistance Mechanisms Against Plant-Parasitic Nematodes" focused on molecular aspects of the interaction between sedentary nematodes and plants on the model system Arabidopsis and on novel resistance strategies. Funding was provided mainly for exchange visits between collaborating laboratories and for the organization of annual meetings. During the last annual meeting which was held in May 1996 in Toledo, Spain, Carmen Fenoll initiated the production of this volume. The text presents a series of current reviews, each written by one of the participating laboratories, which include the scientific progress achieved in the frame of this CAP but are by no means limited in scope to this work.

It is now widely accepted that the extracellular matrix (ECM) is a key determinant of tissue-specific gene expression. Signals provided by ECM are transduced by integrins, a large and growing superfamily of transmembrane heterodimeric cell surface receptors that link the ECM to structural and fu- tional elements within the cell. A wide range of cellular phenotypes have been shown to be regulated by integrins, including growth, differentiation, mig- tion, invasion, angiogenesis, and apoptosis. Furthermore, abnormalities of integrin expression and function have been implicated in the etiology of va- ous pathologic conditions, including cardiovascular disease, inflammatory disorders, and cancer. Thus integrins have emerged as an important class of molecules with wide ranging implications for understanding basic biological processes. In Integrin Protocols we provide a wide-ranging collection of laboratory protocols intended to assist investigators interested in integrins in working productively with these molecules, in studying their expression, and in pot- tially manipulating that expression to define their role(s) in relevant biolo- cal models. Protocols are provided for the analysis of integrin expression both at the RNA and protein levels (Chaps. 2, 5, and 7). Delcommenne and Streuli describe procedures for making rat monoclonal antibodies specific for mouse integrins; Schneller et al. and Arap and Huang describe methods for western blotting of integrins and RT-PCR analysis. Protocols are included that cover the analysis of the functional properties of integrins (Chaps. 1, 3, 4, 8, and 9 through 11). Koivunen et al.

This volume focuses on procedures for the development and application of several research animal models and in vitro methods that allow researchers to gain insight into the underlying cellular, biochemical, and physiological mechanisms involved in traumatic and ischemic injury. The chapters in this book discuss topics, such as animal models and techniques commonly used to study traumatic brain injury, hemorrhagic shock, ischemic and hemorrhagic strokes, sepsis, burn injury, hind limb ischemia, myocardial-ischemia-reperfusion injury, intracranial pressure, global hypoxia-induced perinatal seizures models, and in vitro models. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and comprehensive, Traumatic and Ischemic Injury: Methods and Protocols is a valuable resource for novices with limited experience to help them initiate new research projects, and established researchers to help them identify comparable approaches and strategies to their studies in this field.

Molecular biology has rapidly advanced since the discovery of the basic flow of information in life, from DNA to RNA to proteins. While there are several important and interesting exceptions to this general flow of information, the importance of these biological macromolecules in dictating the phenotypic nature of living creatures in health and disease is paramount. In the last one and a half decades, and particularly after the completion of the Human Genome Project, there has been an explosion of technologies that allow the broad characterization of these macromolecules in physiology, and the perturbations to these macromolecules that occur in diseases such as cancer. In this volume, we will explore the modern approaches used to characterize these macromolecules in an unbiased, systematic way. Such technologies are rapidly advancing our knowledge of the coordinated and complicated changes that occur during carcinogenesis, and are providing vital information that, when correctly interpreted by biostatistical/bioinformatics analyses, can be exploited for the prevention, diagnosis, and treatment of human cancers. The purpose of this volume is to provide an overview of modern molecular biological approaches to unbiased discovery in cancer research. Advances in molecular biology allowing unbiased analysis of changes in cancer initiation and progression will be overviewed. These include the strategies employed in modern genomics, gene expression analysis, and proteomics.

By the end of the 1980s only two microtubule-dependent motors, the plus end-directed kinesin and the minus end-directed cytoplasmic dynein, had been identified. At the time, these two motors seemed almost sufficient to explain directional motility events on polar microtubule tracks in the cell. No- theless, shortly after, the tip of the iceberg began to emerge with the identi- cation of proteins containing in their sequences a domain found in kinesin. This domain, called the "motor domain," conferred on these proteins the essential property of moving on microtubules, using the energy derived from ATP hydro- sis. Since then, the identification of new proteins belonging to the kinesin superfamily of microtubule-dependent motors has gone at such a pace that nowadays more than 200 entries with motor domain sequences are deposited in the database. Kinesin family members are found in all eukaryotic org- isms tested. They present a wide range of domain organizations with a motor domain located at different positions in the molecule. Their motility prop- ties are also variable in directionality, velocity, and such other characteristics as bundling activity and processivity. Finally, and most important, they p- ticipate in a multitude of cellular functions. Our understanding of many cel- lar events, such as mitotic spindle assembly and neuronal transport, to cite only two, has progressed substantially in the last few years thanks to the id- tification of these motors.

Nanotechnology and nucleic acid based therapies are two emerging fields in science whose combination has the potential to improve quality of life for patients suffering from various diseases that can so far only be treated in an unsatisfactory way. Nucleic acids offer the potential for highly selective treatment of such diseases or the highly specific modulation of gene expression with RNA interference. A key issue for successful nucleic acid therapies is the availability of a suitable delivery system. Here, the field of nanotechnology offers a multitude of possibilities to develop nanosized delivery vectors tailor-made for various local and systemic approaches. In "Nanotechnology for Nucleic Acid Delivery: Methods and Protocols," experts in the field cover the area of nanoparticulate delivery of nucleic acids in terms of biosafety, particle synthesis as well as its application in cell culture. 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, "Nanotechnology for" "Nucleic Acid Delivery: Methods and Protocols" seeks to serve both professionals and novices with its well-honed methodologies."

Cell senescence is the process whereby cells permanently lose the possibility to proliferate without undergoing cell death, and occurs in a plethora of distinct model organisms. In Cell Senescence: Methods and Protocols, expert researchers in the field detail the methods that are now commonly used to study cell senescence, in model organisms encompassing bacteria, fungi, worms, flies, zebrafish, and mammalian cells. These techniques cover the study of all the morphological, biochemical and functional manifestations of senescence at the cellular level and include protocols for population analyses and high-throughput approaches in suitable model organisms. Written in the highly 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 laboratory protocols, and key tips on troubleshooting and avoiding known pitfalls.

This volume provides a comprehensive and technical presentation of numerous aspects of reproductive cell tissue cryopreservation, and presents readers with current procedures and detailed discussions of novel techniques and the latest innovations. The chapters in this book are divided into five parts and cover subjects such as: immature oocyte cryopreservation, human sperm vitrification and slow-freezing, directional freezing of ovarian tissue, automated vitrification systems, and detailed protocols on popular and commercially available cryopreservation/vitrification systems. Written in the highly 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 laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Cutting-edge and practical, Cryopreservation of Mammalian Gametes and Embryos: Methods and Protocols includes chapters written by leading experts in the field and is a valuable resource for anyone interested in the field of cryopreservation.

When marketing managers and financial managers join forces within any business, the result can often be poor communication on financial criteria and goals. The risk of this situation occurring is inevitably present when those with different professional backgrounds and roles are working in accordance with their own norms. In his seminal 1956 paper on general systems theory, the economist Kenneth Boulding referred to the phenomenon of "specialised ears and generalised deafness", which can be seen to exist when marketing managers are financially illiterate or when financial managers lack the necessary insights to design, implement and operate accounting systems which are useful to marketing managers in carrying out their roles. It is increasingly difficult to attach credence to the idea of marketing managers who lack financial skills, or financial managers who fail to relate to the context in which marketing managers operate. Understanding the marketing/accounting interface is therefore important in generating emergent properties from the interaction of marketers and accountants whereby the whole is greater than the sum of the parts. The chapters in this volume seek to address this challenge. This book was originally published as a special issue of the Journal of Marketing Management.