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  • Annual Reviews  (3,180)
  • 2000-2004  (3,180)
  • 1
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Views of how cell membranes are organized are presently changing. The lipid bilayer that constitutes these membranes is no longer understood to be a homogeneous fluid. Instead, lipid assemblies, termed rafts, have been introduced to provide fluid platforms that segregate membrane components and dynamically compartmentalize membranes. These assemblies are thought to be composed mainly of sphingolipids and cholesterol in the outer leaflet, somehow connected to domains of unknown composition in the inner leaflet. Specific classes of proteins are associated with the rafts. This review critically analyzes what is known of phase behavior and liquid-liquid immiscibility in model systems and compares these data with what is known of domain formation in cell membranes.
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  • 2
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Emerging methods in cryo-electron microscopy allow determination of the three-dimensional architectures of objects ranging in size from small proteins to large eukaryotic cells, spanning a size range of more than 12 orders of magnitude. Advances in determining structures by "single particle" microscopy and by "electron tomography" provide exciting opportunities to describe the structures of subcellular assemblies that are either too large or too heterogeneous to be investigated by conventional crystallographic methods. Here, we review selected aspects of progress in structure determination by cryo-electron microscopy at molecular resolution, with a particular emphasis on topics at the interface of single particle and tomographic approaches. The rapid pace of development in this field suggests that comprehensive descriptions of the structures of whole cells and organelles in terms of the spatial arrangements of their molecular components may soon become routine.
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  • 3
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Topoisomerases are enzymes that use DNA strand scission, manipulation, and rejoining activities to directly modulate DNA topology. These actions provide a powerful means to effect changes in DNA supercoiling levels, and allow some topoisomerases to both unknot and decatenate chromosomes. Since their initial discovery over three decades ago, researchers have amassed a rich store of information on the cellular roles and regulation of topoisomerases, and have delineated general models for their chemical and physical mechanisms. Topoisomerases are now known to be necessary for the survival of cellular organisms and many viruses and are rich clinical targets for anticancer and antimicrobial treatments. In recent years, crystal structures have been obtained for each of the four types of topoisomerases in a number of distinct conformational and substrate-bound states. In addition, sophisticated biophysical methods have been utilized to study details of topoisomerase reaction dynamics and enzymology. A synthesis of these approaches has provided researchers with new physical insights into how topoisomerases employ chemistry and allostery to direct the large-scale molecular motions needed to pass DNA strands through each other.
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  • 4
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Quantitative electroencephalogram (qEEG) plays a significant role in EEG-based clinical diagnosis and studies of brain function. In past decades, various qEEG methods have been extensively studied. This article provides a detailed review of the advances in this field. qEEG methods are generally classified into linear and nonlinear approaches. The traditional qEEG approach is based on spectrum analysis, which hypothesizes that the EEG is a stationary process. EEG signals are nonstationary and nonlinear, especially in some pathological conditions. Various time-frequency representations and time-dependent measures have been proposed to address those transient and irregular events in EEG. With regard to the nonlinearity of EEG, higher order statistics and chaotic measures have been put forward. In characterizing the interactions across the cerebral cortex, an information theory-based measure such as mutual information is applied. To improve the spatial resolution, qEEG analysis has also been combined with medical imaging technology (e.g., CT, MR, and PET). With these advances, qEEG plays a very important role in basic research and clinical studies of brain injury, neurological disorders, epilepsy, sleep studies and consciousness, and brain function.
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  • 5
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: The recent rapid increase in interest in tomographic imaging of small animals and of human (and large animal) organ biopsies is driven largely by drug discovery, cancer detection/monitoring, phenotype identification and/or characterization, and development of disease detection methods and monitoring efficacies of drugs in disease treatment. In biomedical applications, micro-computed tomography (CT) scanners can function as scaled-down (i.e., mini) clinical CT scanners that provide a three-dimensional (3-D) image of most, if not the entire, torso of a mouse at image resolution (50-100 mum) scaled proportional to that of a human CT image. Micro-CT scanners, on the other hand, image specimens the size of intact rodent organs at spatial resolutions from cellular (20 mum) down to subcellular dimensions (e.g., 1 mum) and fill the resolution-hiatus between microscope imaging, which resolves individual cells in thin sections of tissue, and mini-CT imaging of intact volumes.
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  • 6
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Since its inception just over a half century ago, the field of biomaterials has seen a consistent growth with a steady introduction of new ideas and productive branches. This review describes where we have been, the state of the art today, and where we might be in 10 or 20 years. Herein, we highlight some of the latest advancements in biomaterials that aim to control biological responses and ultimately heal. This new generation of biomaterials includes surface modification of materials to overcome nonspecific protein adsorption in vivo, precision immobilization of signaling groups on surfaces, development of synthetic materials with controlled properties for drug and cell carriers, biologically inspired materials that mimic natural processes, and design of sophisticated three-dimensional (3-D) architectures to produce well-defined patterns for diagnostics, e.g., biological microelectromechanical systems (bioMEMs), and tissue engineering.
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  • 7
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Robotic devices are helping shed light on human motor control in health and injury. By using robots to apply novel force fields to the arm, investigators are gaining insight into how the nervous system models its external dynamic environment. The nervous system builds internal models gradually by experience and uses them in combination with impedance and feedback control strategies. Internal models are robust to environmental and neural noise, generalized across space, implemented in multiple brain regions, and developed in childhood. Robots are also being used to assist in repetitive movement practice following neurologic injury, providing insight into movement recovery. Robots can haptically assess sensorimotor performance, administer training, quantify amount of training, and improve motor recovery. In addition to providing insight into motor control, robotic paradigms may eventually enhance motor learning and rehabilitation beyond the levels possible with conventional training techniques.
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  • 8
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Technology , Medicine
    Notes: Optical projection tomography is a new approach for three-dimensional (3-D) imaging of small biological specimens. It fills an imaging gap between MRI and confocal microscopy, being most suited to specimens that are from 1 to 10 mm across. The tomographic principles of optical projection tomography (OPT) are explained, its most important applications in biomedical research explored, and comparisons drawn of its pros and cons compared to a number of alternative imaging technologies.
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  • 9
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The genomes from three mammals (human, mouse, and rat), two worms, and several yeasts have been sequenced, and more genomes will be completed in the near future for comparison with those of the major model organisms. Scientists have used various methods to align and compare the sequenced genomes to address critical issues in genome function and evolution. This review covers some of the major new insights about gene content, gene regulation, and the fraction of mammalian genomes that are under purifying selection and presumed functional. We review the evolutionary processes that shape genomes, with particular attention to variation in rates within genomes and along different lineages. Internet resources for accessing and analyzing the treasure trove of sequence alignments and annotations are reviewed, and we discuss critical problems to address in new bioinformatic developments in comparative genomics.
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  • 10
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Nutritional genomics has tremendous potential to change the future of dietary guidelines and personal recommendations. Nutrigenetics will provide the basis for personalized dietary recommendations based on the individual's genetic make up. This approach has been used for decades for certain monogenic diseases; however, the challenge is to implement a similar concept for common multifactorial disorders and to develop tools to detect genetic predisposition and to prevent common disorders decades before their manifestation. The preliminary results involving gene-diet interactions for cardiovascular diseases and cancer are promising, but mostly inconclusive. Success in this area will require the integration of different disciplines and investigators working on large population studies designed to adequately investigate gene-environment interactions. Despite the current difficulties, preliminary evidence strongly suggests that the concept should work and that we will be able to harness the information contained in our genomes to achieve successful aging using behavioral changes; nutrition will be the cornerstone of this endeavor.
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  • 11
    Electronic Resource
    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Besides its obvious intrinsic value, knowledge of population history, and of the demographic and evolutionary changes that accompany it, has proven fundamental to address applied research in human genetics. In this review we place current European genetic diversity in the context of the global human genome diversity and review the evidence supporting a recent African origin of the Europeans. We then discuss the results and the interpretation of genetic studies attempting to quantify the relative importance of various gene flow processes, both within Europe and from Asia into Europe, focusing especially on the initial, Paleolithic colonization of the continent, and on later, Paleolithic postglacial and Neolithic dispersals. Finally, we discuss how knowledge of the patterns of genetic diversity in Europe, and of their inferred generating processes, can be extremely useful in planning health care and in biomedical research.
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  • 12
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Prostate cancer is a heterogeneous disease with multiple loci contributing to susceptibility. Traditionally, genome-wide scans using high-risk families have utilized stratification by number of affected individuals, family history of other cancers, or family age at diagnosis to improve genetic homogeneity. In addition to locus heterogeneity, for later onset diseases such as prostate cancer, a major limitation to mapping efforts is that key parental DNA samples are rarely available. The lack of available samples from upper generations reduces inheritance information, and as a result, the standard 10-cM genome scan does not provide full power to detect linkage. To increase the ability to find disease-associated loci, much denser genome-wide scans must be undertaken in multiple ethnic groups. In addition, new ways of defining homogenous subsets of families need to be developed.
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  • 13
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Model organisms, especially the budding yeast, are leading systems in the transformation of biology into an information science. With the availability of genome sequences and genome-scale data generation technologies, the extraction of biological insight from complex integrated molecular networks has become a major area of research. Here I examine key concepts and review research developments. I propose specific areas of research effort to drive network analysis in directions that will promote modeling with increasing predictive power.
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  • 14
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Since Watson & Crick's 1953 description of the structure of DNA, significant progress has been achieved in the control of congenital disorders, most of which has benefited industrialized countries. Little advantage accrued to developing nations, most of which in the same time frame achieved a significant epidemiological transition, resulting in congenital disorders attaining public health significance. The burden of congenital disorders in these lower-resource countries is high and they need to develop medical genetic services. We present a new pragmatic approach for the care and prevention of congenital disorders in these countries, pioneered initially by the World Health Organization.
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  • 15
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Atherosclerosis, the primary cause of coronary artery disease (CAD) and stroke, is a disorder with multiple genetic and environmental contributions. Genetic-epidemiologic studies have identified a surprisingly long list of genetic and nongenetic risk factors for CAD. However, such studies indicate that family history is the most significant independent risk factor (15, 52, 77). Many Mendelian disorders associated with atherosclerosis, such as familial hypercholesterolemia (FH), have been characterized, but they explain only a small percentage of disease susceptibility (although a substantial fraction of early CAD). Most cases of myocardial infarction (MI) and stroke result from the interactions of multiple genetic and environmental factors, none of which can cause disease by itself. Successful discovery of these genetic factors will require using complementary approaches with animal models, large-scale human genetic studies, and functional experiments. This review emphasizes the common, complex forms of CAD.
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  • 16
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The genome sequences of important model systems are available and the focus is now shifting to large-scale experiments enabled by this data. Following in the footsteps of genomics, we have functional genomics, proteomics, and even metabolomics, roughly paralleling the biological hierarchy of the transcription, translation, and production of small molecules. Proteomics is initially concerned with determining the structure, expression, localization, biochemical activity, interactions, and cellular roles of as many proteins as possible. There has been great progress owing to novel instrumentation, experimental strategies, and bioinformatics methods. The area of protein-protein interactions has been especially fruitful. First pass interaction maps of some model organisms exist, and the proteins in many important organelles are about to be determined. Researchers are also beginning to integrate large-scale data sets from various "omics" disciplines in targeted investigations of specific biomedical areas and in pursuit of a general framework for systems biology.
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  • 17
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    Electronic Resource
    Palo Alto, Calif. : Annual Reviews
    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Genetic screening utilizes analytical approaches adapted for high throughput to identify carrier and affected individuals in a targeted population. Currently, genetic screening focuses on carrier screening, prenatal screening, and newborn screening. Newborn screening should serve as a model for all genetic screening, with more than forty years of experience and numerous lessons learned. As with all genetic screening, there are policy concerns in newborn screening regarding which disorders and technologies should be selected, and how centralized or decentralized the process to set policy should be. The need to share experiences and develop databases transcends all other policy considerations in genetic screening. The future will see population-based screening for adult-onset disorders. However, there needs to be extensive research to define predictive risk for various ethnocultural groups and to determine effective interventions. Ethical concerns regarding the timing of population screening, as well as the scope of use of information, will need to be resolved if genomic medicine will achieve its promise of a predictive, preventive, and personalized medicine.
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  • 18
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 49 (2004), S. 27-49 
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Recently, there has been exciting progress in our understanding of the behavioral and evolutionary ecology of immature parasitoids. Developing parasitoids face a diversity of ecological constraints, and parasitism success involves decisions and responses made by immature parasitoids to find a host and solve conflicts with five potential antagonists: host, mother, siblings, competitors, and natural enemies. In this review we synthesize and interpret results from studies on (a) the convergent evolution of host selection behavior of first-instar larvae and females in hymenopteran, dipteran, and coleopteran families; (b) the competitive interactions between larval parasitoids and the evolution of gregariousness; (c) the susceptibility of parasitized hosts to predation; and (d) the ability of parasitoids to manipulate the behavior of the host. We discuss how ecological interactions between juvenile parasitoids and their hosts, competitors, and natural enemies influence the evolution of parasitoid life-history strategies, and why the integration of functional aspects of the ecology of immature parasitoids provides a reliable framework for effective host-parasitoid population models and formulation of biological control solutions.
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  • 19
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 49 (2004), S. 51-70 
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: With the advent of significant collaborations between researchers who study insect walking and robotics engineers interested in constructing adaptive legged robots, insect walking is once again poised to make a more significant scientific contribution than the numbers of participants in the field might suggest. This review outlines current knowledge of the physiological basis of insect walking with an emphasis on recent new developments in biomechanics and genetic dissection of behavior, and the impact this knowledge is having on robotics. Engineers have begun to team with neurobiologists to build walking robots whose physical design and functional control are based on insect biology. Such an approach may have benefits for engineering, by leading to the construction of better-performing robots, and for biology, by allowing real-time and real-world tests of critical hypotheses about how locomotor control is effected. It is argued that in order for the new field of biorobotics to have significant influence it must adopt criteria for performance and an experimental approach to the development of walking robots.
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  • 20
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Entomology 49 (2004), S. 193-217 
    ISSN: 0066-4170
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: The concept that an insect species' genome could be altered in a manner that would result in the control of that species (i.e., autocidal control) or in the replacement of a pestiferous strain of the species with a more benign genotype was first proposed in the mid-twentieth century. A major research effort in population genetics and ecology followed and led to the development of a set of classical genetic control approaches that included use of sterile males, conditional lethal genes, translocations, compound chromosomes, and microbe-mediated infertility. Although there have been a number of major successes in application of classical genetic control, research in this area has declined in the past 20 years for technical and societal reasons. Recent advances in molecular biology and transgenesis research have renewed interest in genetically based control methods because these advances may remove some major technical problems that have constrained effective genetic manipulation of pest species. Population genetic analyses suggest that transgenic manipulations may enable development of strains that would be 10 to over 100 times more efficient than strains developed by classical methods. Some of the proposed molecular approaches to genetic control involve modifications of classical approaches such as conditional lethality, whereas others are novel. Experience from the classical era of genetic control research indicates that the population structure and population dynamics of the target population will determine which, if any, genetic control approaches would be appropriate for addressing a specific problem. As such, there continues to be a need for ongoing communication between scientists who are developing strains and those who study the native pest populations.
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  • 21
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 29-53 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Coating is the process of applying thin liquid layers to a substrate, often a moving web. Complex coating processes can be approached through examination of their fluid mechanical components. The flow elements reviewed in this article include the boundary layer along a moving wall, the dynamic wetting line, withdrawal from a pool, flow metered by a narrow channel, die flow, flow on an incline, the freely falling liquid curtain, premetered coating with a small gap, and flow after coating. Although some flow elements are well studied and understood, others require additional investigation. Genuinely predictive modeling of complex coating processes is not yet possible and coating practice remains largely empirical. Nonetheless, coating science is sufficiently advanced that physical insights and mathematical models greatly benefit design and practice.
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  • 22
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 55-79 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Since Leibovich's comprehensive review of Langmuir circulation in 1983 there have been substantial advances in modeling (notably the construction of Large Eddy Simulation models) and in observations using novel techniques that together have led to a radical change in understanding the phenomena. It is now regarded as one of the several turbulent processes driven by wind and waves in the upper layers of large bodies of water, influential in producing and maintaining the uniform surface mixed layer and in driving dispersion.
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  • 23
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 81-96 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: Early concepts in shock wave drag reduction enabled modern aeronautical systems, and continuing research progress in this arena is crucial for significant improvements in long haul transports and various military platforms and weapons. The research area is rich in concepts/approaches, but many of these have not progressed into the realm of application. This is due in part to a lack of knowledge on the part of the fluids research community concerning the multidisciplinary "real-world" design space/metrics and a consequent lack of the requisite breadth and depth of research information required to evaluate/apply the concept. The article reviews the extant wave drag reduction approaches that are (a) well understood/applied, (b) under active study/indicate considerable promise, and (c) those in the nascent stage only.
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  • 24
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 97-119 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: This paper reviews the current state of the art in accidental explosion modeling using methods based on computational fluid dynamics (CFD) in the petrochemical process industries. We discuss the problem in terms of its industrial importance and its technical difficulty, which stems mainly from the large range of length and timescales that must be represented. Explicit representation of all scales is not feasible due to limitations of computational cost, and modeling of unresolved physical features is required. We also discuss geometry modeling using the porosity/distributed resistance (PDR) method and review relevant combustion modeling. We describe an advanced CFD approach using unstructured adaptive gridding and discuss its usefulness in the context of results obtained for both two dimensional and three dimensional simulations of gas explosion phenomena in complex geometries.
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  • 25
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 255-279 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: This paper is a short and nonexhaustive survey of some recent developments in optimal shape design (OSD) for fluids. OSD is an interesting field both mathematically and for industrial applications. Existence, sensitivity, and compatibility of discretizations are important theoretical issues. Efficient algorithmic implementations with low complexity are also critical. In this paper we discuss topological optimization, algorithmic differentiation, gradient smoothers, Computer Aided Design (CAD)-free platforms and shock differentiation; all these are applied to a multicriterion optimization for a supersonic business jet.
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  • 26
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Fluid Mechanics 36 (2004), S. 233-253 
    ISSN: 0066-4189
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics , Physics
    Notes: We review the use of ray models for internal waves, particularly formulations for calculating wave amplitudes along the ray. These are expressed in spatial, wave number, and phase-space coordinates. The choice of formulation affects not only the difficulty of the calculations for rays and caustics but also the degree to which the waves satisfy slowly varying assumptions. We describe several examples taken from atmospheric and oceanic applications that illustrate the variety of options for ray models.
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  • 27
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 55 (2004), S. 1-13 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: With the official completion of the Human Genome Project in April 2003, we have both the opportunity and the imperative to translate this unprecedented scientific accomplishment into tangible improvements in human health. Medical benefits from the genome will come in stages and can be conceptualized as occurring in three areas: improved understanding of disease causation at the molecular level, improved diagnosis and disease classification based on genetic profiles, and new therapeutics based on targets identified in the genome. These improvements will require increased physician understanding of genetic principles applied to common diseases.
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  • 28
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    Annual Review of Medicine 55 (2004), S. 255-282 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: The prospects for successful clinical trials of neuroprotective and neurorestorative interventions for patients with acute and chronic myelopathies depend on preclinical animal models of injury and repair that reflect the human condition. Remarkable progress continues in the attempt to promote connections between the brain and the sensory and motor neurons below a spinal cord lesion. Recent experiments demonstrate the potential for biological therapies to regenerate or remyelinate axons and to incorporate new neural cells into the milieu of a traumatic spinal cord injury. The computational flexibility and plasticity of the sensorimotor systems of the brain, spinal cord, and motor unit make functional use of new circuitry feasible in patients. To incorporate residual and new pathways, neural repair strategies must be coupled to rehabilitation therapies that drive activity-dependent plasticity for walking, for reaching and grasping, and for bowel and bladder control. Prevention of pain and dysautonomia are also clinical targets. Research aims to define the temporal windows of opportunity for interventions, test the safety and efficacy of delivery systems of agents and cells, and provide a better understanding of the cascades of gene expression and cell interactions both acutely and chronically after injury. These bench-to-bedside studies are defining the neurobiology of spinal cord injury rehabilitation.
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  • 29
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    Annual Review of Medicine 55 (2004), S. 333-353 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: The United States currently has relatively low rates of meningococcal disease caused by Neisseria meningitidis. Serogroups Y, C, and B are most common. Although most cases are sporadic, a minority are associated with outbreaks. Pediatric populations have disproportionately higher rates of disease, but nearly two thirds of all cases occur in persons aged 15 years and older. The major challenge to control of domestic meningococcal disease is the absence of a vaccine to prevent sporadic cases spanning many age groups. The quadrivalent A/C/Y/W-135 meningococcal polysaccharide vaccine is licensed in the United States, but because of its limited efficacy in children under two years of age, it is recommended for high-risk groups and outbreak response rather than routine childhood immunization. New conjugate meningococcal vaccines have successfully reduced endemic disease in the United Kingdom, and similar vaccines promise to have a dramatic impact on the burden of meningococcal disease in the United States.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 55 (2004), S. 419-432 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Systemic mastocytosis is a clonal disorder of the mast cell and its progenitor. The symptoms of systemic mastocytosis are due to the pathologic accumulation and activation of mast cells in various tissues such as bone marrow, skin, gastrointestinal tract, liver, and spleen. Recent studies revealed striking differences between the molecular and cellular biology of mast cells in patients with mastocytosis and those of healthy individuals. These findings are being used in formulating diagnostic criteria as well as designing novel treatment approaches to the disease.
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    Annual Review of Medicine 55 (2004), S. 477-503 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Rituximab (RituxanR) is a human-mouse chimeric monoclonal antibody that targets the B-cell CD20 antigen and causes rapid and specific B-cell depletion. Rituximab was approved in the United States in 1997 to treat low-grade or follicular, relapsed or refractory, CD20-positive B-cell non-Hodgkin's lymphoma (NHL). Since then, further clinical experience with rituximab has been incorporated into the prescribing information, which now stipulates an extended eight-week schedule, treatment of patients with refractory or relapsed bulky disease measuring 〉10 cm, and retreatment of patients who responded to rituximab previously. In 1998, the European Union approved rituximab (MabTheraR) to treat stage III/IV, follicular, chemotherapy-resistant, or relapsed NHL. Recently, the European Union also approved the use of rituximab in combination with standard chemotherapy for aggressive NHL. Many clinical trials have evaluated rituximab, alone or with other therapies, in indolent and aggressive NHL as well as other B-cell lymphoproliferative disorders. New studies are evaluating rituximab's role in first-line therapy, maintenance therapy, and stem-cell transplantation procedures. The use of rituximab against autoimmune disorders, such as rheumatoid arthritis, immune thrombocytopenic purpura, autoimmune hemolytic anemia, systemic lupus erythematosus, and multiple sclerosis, is also under investigation.
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    Palo Alto, Calif. : Annual Reviews
    Annual Review of Medicine 55 (2004), S. 97-112 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Mass spectrometry-based diagnostics has the potential to revolutionize molecular medicine. Using modern mass-spectrometer technologies, clinical tests can be developed that are practical, robust, accurate, and inexpensive. Serum proteomic pattern profiling couples mass spectrometry with adaptive artificial-intelligence-based bioinformatics, which can now be employed to detect pathological states reflected in the serum proteome. With this approach, rapid and cost-effective tests with exquisite clinical sensitivity and specificity are emerging. These tools may dramatically change how disease is detected, monitored, and managed.
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    Annual Review of Medicine 55 (2004), S. 179-189 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Treatment of end-stage renal disease with dialysis is characterized by high mortality rate, low quality of life, and high cost. Recent randomized controlled studies showed that increasing the dialysis dose above the currently recommended levels in thrice-weekly hemodialysis does not decrease the patient mortality rate. Short daily hemodialysis or daily home nocturnal hemodialysis are promising alternatives. Both improve quality of life and control blood pressure and anemia; nocturnal hemodialysis additionally controls serum phosphates without phosphate binders, allows a free diet, and corrects sleep apnea. Although the direct cost of daily hemodialysis is higher than that of conventional hemodialysis, the cost of total care, especially when delivered at home, seems to be lower. Further confirmation of these results is important. Restructuring of the dialysis reimbursement system is necessary to make the use of daily hemodialysis possible. Hemofiltration techniques, sorbents, and the renal tubular assist device may also help change the current grim statistics.
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    Annual Review of Medicine 55 (2004), S. 209-222 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Understanding of lead toxicity has advanced substantially over the past three decades, and focus has shifted from high-dose effects in clinically symptomatic individuals to the consequences of exposure at lower doses that cause no symptoms, particularly in children and fetuses. The availability of more sensitive analytic methods has made it possible to measure lead at much lower concentrations. This advance, along with more refined epidemiological techniques and better outcome measures, has lowered the least observable effect level until it approaches zero. As a consequence, the segment of the population who are diagnosed with exposure to toxic levels has expanded. At the same time, environmental efforts, most importantly the removal of lead from gasoline, have dramatically reduced the amount of lead in the biosphere. The remaining major source of lead is older housing stock. Although the cost of lead paint abatement is measured in billions of dollars, the monetized benefits of such a Herculean task have been shown to far outweigh the costs.
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    Annual Review of Medicine 55 (2004), S. 303-317 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Potent antiretroviral agents markedly suppress HIV and have dramatically improved the clinical course, prognosis, and survival of HIV-infected patients. Unfortunately, highly active antiretroviral therapy is often compromised by metabolic complications, including insulin resistance, dyslipidemia, and fat redistribution. Together these changes have been termed the HIV-lipodystrophy syndrome, which is estimated to affect a majority of patients treated with potent combination antiretroviral therapy. Routine testing of fasting glucose is recommended for all HIV-infected patients, particularly those who are obese, have a family history of diabetes mellitus, or are receiving protease inhibitor therapy. Preliminary investigations have demonstrated the potential utility of insulin-sensitizing agents and lipid-lowering therapies to ameliorate these metabolic disturbances. Patients with HIV infection who demonstrate fat redistribution and develop hyperinsulinemia and dyslipidemia may be at increased risk of cardiovascular disease. However, the long-term effects on cardiovascular disease have not yet been determined.
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    Annual Review of Medicine 55 (2004), S. 355-372 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: An increasing body of evidence suggests that a vaccine that elicits anti-HIV-1 cellular immunity could provide the basis for an effective AIDS vaccine. Comparative immunization experiments testing a variety of vaccine approaches have demonstrated that replication-incompetent adenovirus vectors are an effective means for eliciting cytotoxic T-lymphocyte (CTL) immune responses against HIV-1 antigens. These immune responses effectively control viremia in nonhuman primates following challenge with simian AIDS viruses. Such data, coupled with epidemiology studies that identify HIV-1 gag, pol, and nef as the best antigens for broadly directed cellular immune responses, provide guidance for the development of a potential AIDS vaccine.
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    Annual Review of Medicine 55 (2004), S. 459-475 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Over the past decade, considerable advances have been made in the field of allogeneic hematopoietic stem cell transplantation. Recognition that transplanted donor immune cells can cure patients with leukemia has led to the development of nonmyeloablative or "low-intensity" conditioning regimens, which have expanded the application of allogeneic transplantation to a growing number of hematological malignancies. The improved safety and preliminary success of this transplant approach have justified applying allogeneic immunotherapy to patients with treatment-refractory solid tumors.
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    Annual Review of Medicine 55 (2004), S. 519-526 
    ISSN: 0066-4219
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine
    Notes: Neutropenic patients continue to be at increased risk for developing serious infections despite substantial advances in supportive care. Epidemiologic shifts occur periodically and need to be detected early because they influence prophylactic, empiric, and specific therapy strategies. Although effective in preventing bacterial and some fungal infections, prophylaxis must be used with caution because it is associated with the emergence of resistance. The choices for empiric therapy include combination regimens and monotherapy. Specific choices depend on local factors (epidemiology, susceptibility/resistance patterns, availability). Various treatment settings (hospital-based, early discharge, outpatient) are also available, and the choice depends on the patient's risk category. Early diagnosis and treatment of many fungal and viral infections remains suboptimal. Infection control and prevention are important strategies, especially with the emergence of multidrug-resistant organisms.
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    Annual Review of Physiology 66 (2004), S. 571-599 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: Many cell types in the kidney express adenosine receptors, and adenosine has multiple effects on renal function. Although adenosine is produced within the kidney by several biochemical reactions, recent studies support a novel mechanism for renal adenosine production, the extracellular cAMP-adenosine pathway. This extracellular cAMP-adenosine pathway is initiated by efflux of cAMP from cells following activation of adenylyl cyclase. Extracellular cAMP is then converted to adenosine by the serial actions of ecto-phosphodiesterase and ecto-5'-nucleotidase. When extracellular cAMP is converted to adenosine near the biophase of cAMP production and efflux, this local extracellular cAMP-adenosine pathway permits tight coupling of the site of adenosine production to the site of adenosine receptors. cAMP in renal compartments may also be formed by tissues/organs remote from the kidney. For example, stimulation of hepatic adenylyl cyclase by the pancreatic hormone glucagon increases circulating cAMP, which is filtered at the glomerulus and concentrated in the tubular lumen as water is extracted from the ultrafiltrate. Conversion of hepatic-derived cAMP to adenosine in the kidney completes a pancreatohepatorenal cAMP-adenosine pathway that may serve as an endocrine link between the pancreas, liver, and kidney.
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    Annual Review of Physiology 66 (2004), S. 647-663 
    ISSN: 0066-4278
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Medicine , Biology
    Notes: The lung is a complex organ consisting of numerous cell types that function to ensure sufficient gas exchange to oxygenate the blood. In order to accomplish this function, the lung must be exposed to the external environment and at the same time maintain a homeostatic balance between its function in gas exchange and the maintenance of inflammatory balance. During the past two decades, as molecular methodologies have evolved with the sequencing of entire genomes, the use of in vivo models to elucidate the molecular mechanisms involved in pulmonary physiology and disease have increased. The mouse has emerged as a potent model to investigate pulmonary physiology due to the explosion in molecular methods that now allow for the developmental and tissue-specific regulation of gene transcription. Initial efforts to manipulate gene expression in the mouse genome resulted in the generation of transgenic mice characterized by the constitutive expression of a specific gene and knockout mice characterized by the ablation of a specific gene. The utility of these original mouse models was limited, in many cases, by phenotypes resulting in embryonic or neonatal lethality that prevented analysis of the impact of the genetic manipulation on pulmonary biology. Second-generation transgenic mouse models employ multiple strategies that can either activate or silence gene expression thereby providing extensive temporal and spatial control of the experimental parameters of gene expression. These highly regulated mouse models are intended to serve as a foundation for further investigation of the molecular basis of human disease such as tumorigenesis. This review describes the principles, progress, and application of systems that are currently employed in the conditional regulation of gene expression in the investigation of lung cancer.
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    Annual Review of Anthropology 33 (2004), S. 73-102 
    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: This review addresses methods and theories for the archaeological study of ancient state economies, from the earliest states through the Classical period and beyond. Research on this topic within anthropological archaeology has been held back by reliance on simple concepts and an impoverished notion of the extent of variation in ancient state economies. First I review a long-standing debate between scholars who see similarities with modern capitalist economies (modernists and formalists) and those who see ancient economies as radically different from their modern counterparts (primitivists and substantivists). I suggest that the concept of the level of commercialization provides an avenue for transcending this debate and moving research in more productive directions. Next I review work on the traditional archaeological topics of production and exchange. A discussion of the scale of the economy (households, temple and palace institutions, state finance, cities and regional systems, and international economies) reveals considerable variation between and within ancient states. I review key topics in current archaeological political economy, including commercial exchange, money, property, labor, and the nature of economic change, and close with suggestions for future research.
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    Annual Review of Anthropology 33 (2004), S. 173-199 
    ISSN: 0084-6570
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Ethnic Sciences , Biology
    Notes: In this review, we examine the earliest states in Mesoamerica and how they developed. We present a definition of the state and explain why first-generation or primary states have special significance in anthropology and archaeology; we also discuss how anthropological archaeologists can detect the emergence of state organization in the archaeological record. We review the archaeological data bearing on early state formation in Oaxaca, the Southern Gulf Coast, the Southeastern Lowlands, and the Basin of Mexico. Although we acknowledge that more data are needed from all regions, we conclude that Oaxaca currently provides the most compelling evidence of primary state formation in Mesoamerica.
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: Visible and near-infrared spectra of reflected sunlight from asteroid surfaces exhibit features that hold the promise for identifying surface mineralogy. However, the very surfaces that are observed by remote-sensing are also subject to impingement by micrometeoroids and solar wind particles, which are believed to play the dominant role in space weathering, which is the time-dependent modification of an asteroid's reflectance spectrum. Such space weathering has confused the interpretations of telescopic spectra of asteroids, especially concerning the possible association of common ordinary chondritic meteorites with so-called S-type asteroids. Recent spacecraft studies of asteroids (especially of Eros by NEAR-Shoemaker) have documented aspects of space weathering processes, but we still do not understand the physics of space weathering well enough to confidently assay mineralogy of diverse asteroids by remote-sensing. A review of the intellectual history of this topic reveals the complexity of interdisciplinary research on far-away astronomical bodies.
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    ISSN: 0084-6597
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Geosciences , Physics
    Notes: The migration of the Mendocino triple junction through central and northern California over the past 25-30 million years has led to a profound change in plate interactions along coastal California. The tectonic consequences of the abrupt change from subduction plate interactions north of the triple junction to the development of the San Andreas transform system south of the triple junction can be seen in the geologic record and geophysical observations. The primary driver of this tectonism is a coupling among the subducting Juan de Fuca (Gorda), North American, and Pacific plates that migrates with the triple junction. This coupling leads to ephemeral thickening of the overlying North American crust, associated uplift and subsequent subsidence, and a distinctive sequence of fault development and volcanism.
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    Annual Review of Neuroscience 27 (2004), S. 549-579 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neuronal circuits are shaped by experience during critical periods of early postnatal life. The ability to control the timing, duration, and closure of these heightened levels of brain plasticity has recently become experimentally accessible, especially in the developing visual system. This review summarizes our current understanding of known critical periods across several systems and species. It delineates a number of emerging principles: functional competition between inputs, role for electrical activity, structural consolidation, regulation by experience (not simply age), special role for inhibition in the CNS, potent influence of attention and motivation, unique timing and duration, as well as use of distinct molecular mechanisms across brain regions and the potential for reactivation in adulthood. A deeper understanding of critical periods will open new avenues to "nurture the brain"-from international efforts to link brain science and education to improving recovery from injury and devising new strategies for therapy and lifelong learning.
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    Annual Review of Neuroscience 27 (2004), S. 419-451 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: We explore the extent to which neocortical circuits generalize, i.e., to what extent can neocortical neurons and the circuits they form be considered as canonical? We find that, as has long been suspected by cortical neuroanatomists, the same basic laminar and tangential organization of the excitatory neurons of the neocortex is evident wherever it has been sought. Similarly, the inhibitory neurons show characteristic morphology and patterns of connections throughout the neocortex. We offer a simple model of cortical processing that is consistent with the major features of cortical circuits: The superficial layer neurons within local patches of cortex, and within areas, cooperate to explore all possible interpretations of different cortical input and cooperatively select an interpretation consistent with their various cortical and subcortical inputs.
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    Annual Review of Neuroscience 27 (2004), S. 193-222 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Anxiety and its disorders have long been known to be familial. Recently, genetic approaches have been used to clarify the role of heredity in the development of anxiety and to probe its neurobiological underpinnings. Twin studies have shown that a significant proportion of the liability to develop any given anxiety disorder is due to genetic factors. Ongoing efforts to map anxiety-related loci in both animals and humans are underway with limited success to date. Animal models have played a large role in furthering our understanding of the genetic basis of anxiety, demonstrating that the genetic factors underlying anxiety are complex and varied. Recent advances in molecular genetic techniques have allowed increasing specificity in the manipulation of gene expression within the central nervous system of the mouse. With this increasing specificity has come the ability to ask and answer precise questions about the mechanisms of anxiety and its treatment.
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    Annual Review of Neuroscience 27 (2004), S. 611-647 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Single-unit recording studies in the macaque have carefully documented the modulatory effects of attention on the response properties of visual cortical neurons. Attention produces qualitatively different effects on firing rate, depending on whether a stimulus appears alone or accompanied by distracters. Studies of contrast gain control in anesthetized mammals have found parallel patterns of results when the luminance contrast of a stimulus increases. This finding suggests that attention has co-opted the circuits that mediate contrast gain control and that it operates by increasing the effective contrast of the attended stimulus. Consistent with this idea, microstimulation of the frontal eye fields, one of several areas that control the allocation of spatial attention, induces spatially local increases in sensitivity both at the behavioral level and among neurons in area V4, where endogenously generated attention increases contrast sensitivity. Studies in the slice have begun to explain how modulatory signals might cause such increases in sensitivity.
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    Annual Review of Neuroscience 27 (2004), S. 509-547 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Neurotransmitter release is mediated by exocytosis of synaptic vesicles at the presynaptic active zone of nerve terminals. To support rapid and repeated rounds of release, synaptic vesicles undergo a trafficking cycle. The focal point of the vesicle cycle is Ca2+-triggered exocytosis that is followed by different routes of endocytosis and recycling. Recycling then leads to the docking and priming of the vesicles for another round of exo- and endocytosis. Recent studies have led to a better definition than previously available of how Ca2+ triggers exocytosis and how vesicles recycle. In particular, insight into how Munc18-1 collaborates with SNARE proteins in fusion, how the vesicular Ca2+ sensor synaptotagmin 1 triggers fast release, and how the vesicular Rab3 protein regulates release by binding to the active zone proteins RIM1alpha and RIM2alpha has advanced our understanding of neurotransmitter release. The present review attempts to relate these molecular data with physiological results in an emerging view of nerve terminals as macromolecular machines.
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    Annual Review of Neuroscience 27 (2004), S. 369-392 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: In mammalian visual cortex, neurons are organized according to their functional properties into multiple maps such as retinotopic, ocular dominance, orientation preference, direction of motion, and others. What determines the organization of cortical maps? We argue that cortical maps reflect neuronal connectivity in intracortical circuits. Because connecting distant neurons requires costly wiring (i.e., axons and dendrites), there is an evolutionary pressure to place connected neurons as close to each other as possible. Then, cortical maps may be viewed as solutions that minimize wiring cost for given intracortical connectivity. These solutions can help us in inferring intracortical connectivity and, ultimately, in understanding the function of the visual system.
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    Annual Review of Neuroscience 27 (2004), S. 341-368 
    ISSN: 0147-006X
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: A hostile environment and decreased regenerative capacity may contribute to the failure of axon regeneration in the adult central nervous system. Recent studies leading to the identification of several myelin-associated inhibitors and their signaling molecules provide opportunitities to assess the contribution of these inhibitory molecules in restricting axon regeneration. These findings may ultimately allow for the development of strategies to alleviate the inhibitory effects of such molecules in an effort to encourage axon regeneration after spinal cord and brain injury.
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    Annual Review of Sociology 30 (2004), S. 409-425 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: Investigators interested in developing a general theory of social cohesion are confronted with a complex body of work that involves various definitions of social cohesion, specialized literatures on particular dimensions of social cohesion (e.g., membership turnover, organizational commitment, categorical identifications, interpersonal attachments, network structures), and lines of inquiry focused on the social cohesion of specific types of groups (e.g., families, schools, military units, and sports teams). This review addresses the problem of integrating the individual and group levels at which social cohesion has been defined. It also develops a perspective on social cohesion as a domain of causally interrelated phenomena concerned with individuals' membership attitudes and behaviors, in which the major dimensions of social cohesion occupy different theoretical positions with respect to one another as antecedent, intervening, or outcome variables.
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    Annual Review of Sociology 30 (2004), S. 199-220 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: We define the knowledge economy as production and services based on knowledge-intensive activities that contribute to an accelerated pace of technical and scientific advance, as well as rapid obsolescence. The key component of a knowledge economy is a greater reliance on intellectual capabilities than on physical inputs or natural resources. We provide evidence drawn from patent data to document an upsurge in knowledge production and show that this expansion is driven by the emergence of new industries. We then review the contentious literature that assesses whether recent technological advances have raised productivity. We examine the debate over whether new forms of work that embody technological change have generated more worker autonomy or greater managerial control. Finally, we assess the distributional consequences of a knowledge-based economy with respect to growing inequality in wages and high-quality jobs.
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    Annual Review of Sociology 30 (2004), S. 221-242 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: Over the past four decades, immigration has increased the racial and ethnic diversity in the United States. Once a mainly biracial society with a large white majority and relatively small black minority-and an impenetrable color line dividing these groups-the United States is now a society composed of multiple racial and ethnic groups. Along with increased immigration are rises in the rates of racial/ethnic intermarriage, which in turn have led to a sizeable and growing multiracial population. Currently, 1 in 40 persons identifies himself or herself as multiracial, and this figure could soar to 1 in 5 by the year 2050. Increased racial and ethnic diversity brought about by the new immigration, rising intermarriage, and patterns of multiracial identification may be moving the nation far beyond the traditional and relatively persistent black/white color line. In this chapter, we review the extant theories and recent findings concerning immigration, intermarriage, and multiracial identification, and consider the implications for America's changing color lines. In particular, we assess whether racial boundaries are fading for all groups or whether America's newcomers are simply crossing over the color line rather than helping to eradicate it.
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    Annual Review of Sociology 30 (2004), S. 125-145 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: I review the development of the political opportunity or political process perspective, which has animated a great deal of research on social movements. The essential insight-that the context in which a movement emerges influences its development and potential impact-provides a fruitful analytic orientation for addressing numerous questions about social movements. Reviewing the development of the literature, however, I note that conceptualizations of political opportunity vary greatly, and scholars disagree on basic theories of how political opportunities affect movements. The relatively small number of studies testing political opportunity hypotheses against other explanations have generated mixed results, owing in part to the articulation of the theory and the specifications of variables employed. I examine conflicting specifications of the theory by considering the range of outcomes scholars address. By disaggregating outcomes and actors, I argue, we can reconcile some of the apparent contradictions and build a more comprehensive and robust theory of opportunities and social movements.
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    Annual Review of Sociology 30 (2004), S. 173-197 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: Consumption is a social, cultural, and economic process of choosing goods, and this process reflects the opportunities and constraints of modernity. Viewing consumption as an "institutional field," the review suggests how consumption bridges economic and cultural institutions, large-scale changes in social structure, and discourses of the self. New technologies, ideologies, and delivery systems create consumption spaces in an institutional framework shaped by key social groups, while individual men and women experience consumption as a project of forming, and expressing, identity. Studying the institutional field requires research on consumer products, industries, and sites; on the role of consumption in constructing both the consuming subject and collective identity; and on historical transitions to a consumer society. Ethnography, interviews, and historical analysis show a global consumer culture fostered by media and marketing professionals yet subject to different local interpretations.
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    Annual Review of Sociology 30 (2004), S. 103-124 
    ISSN: 0360-0572
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Sociology
    Notes: New state and market arrangements were twice imposed on the residents of the eastern part of Germany, once when Germany was divided in 1949 and again when it was reunified in 1990; these changes produced a unique natural experiment concerning the effect of policies and institutions on the gendered nature of work. This review synthesizes research on gender equality in paid and unpaid work in East versus West Germany during the decades immediately preceding and following reunification. We consider empirical evidence on gender equality in five major dimensions of work: the prevalence of labor market attachment, time spent in paid work, wages, employment sector and occupation, and time spent in unpaid work in the home. Taken together, developments across these dimensions suggest that, following reunification, the two parts of the country converged toward the gendered arrangement in which men are employed full-time and their female partners hold part-time jobs-with some evidence of continuing differences between East and West.
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 0163-8998
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: Lattice quantum chromodynamics provides first-principles calculations for hadrons containing heavy quarkscharm and bottom quarks. Their mass spectra, decay rates, and some hadronic matrix elements can be calculated on the lattice in a model-independent manner. In this review, we introduce the effective theories that treat heavy quarks on the lattice. We summarize results on the heavy quarkonium spectrum, which verify the validity of the effective theory approach. We then discuss applications to B physics, which is the main target of the lattice theory of heavy quarks. We review progress in lattice calculations of the B meson decay constant, the B parameter, semileptonic decay form factors, and other important quantities.
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    ISSN: 0163-8998
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Physics
    Notes: One can extract unique information about the nuclear interaction from the study of the heaviest elements. They exist solely on the basis of quantum effects, which create a barrier against spontaneous fission. The important questions concern the end of the periodic table and the location of the next closed nucleon shells. Considerable progress was achieved during the past few years in structure studies in this region. This was made possible by the development of detector systems for decay and in-beam studies using recoil separators and heavy ion fusion reactions. We concentrate on these developments and on recent results from structure studies in the region from einsteinium to dubnium. We present recent data on the elements 110 (darmstadtium), 111, and 112, and discuss claims for the synthesis of even heavier elements. We discuss the implications of these studies for predicting the location of the next spherical shells and give a brief outlook on the future.
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    Annual Review of Immunology 22 (2004), S. 247-306 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The twenty-first century is beginning with a sharp turn in the field of cancer therapy. Molecular targeted therapies against specific oncogenic events are now possible. The BCR-ABL story represents a notable example of how research from the fields of cytogenetics, retroviral oncology, protein phosphorylation, and small molecule chemical inhibitors can lead to the development of a successful molecular targeted therapy. Imatinib mesylate (Gleevec, STI571, or CP57148B) is a direct inhibitor of ABL (ABL1), ARG (ABL2), KIT, and PDGFR tyrosine kinases. This drug has had a major impact on the treatment of chronic myelogenous leukemia (CML) as well as other blood neoplasias and solid tumors with etiologies based on activation of these tyrosine kinases. Analysis of CML patients resistant to BCR-ABL suppression by Imatinib mesylate coupled with the crystallographic structure of ABL complexed to this inhibitor have shown how structural mutations in ABL can circumvent an otherwise potent anticancer drug. The successes and limitations of Imatinib mesylate hold general lessons for the development of alternative molecular targeted therapies in oncology.
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    Annual Review of Immunology 22 (2004), S. 817-890 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: This review summarizes the major features of CD1 genes and proteins, the patterns of intracellular trafficking of CD1 molecules, and how they sample different intracellular compartments for self- and foreign lipids. We describe how lipid antigens bind to CD1 molecules with their alkyl chains buried in hydrophobic pockets and expose their polar lipid headgroup whose fine structure is recognized by the TCR of CD1-restricted T cells. CD1-restricted T cells carry out effector, helper, and adjuvant-like functions and interact with other cell types including macrophages, dendritic cells, NK cells, T cells, and B cells, thereby contributing to both innate and adaptive immune responses. Insights gained from mice and humans now delineate the extensive range of diseases in which CD1-restricted T cells play important roles and reveal differences in the role of CD1a, CD1b, and CD1c in contrast to CD1d. Invariant TCRalpha chains, self-lipid reactivity, and rapid effector responses empower a subset of CD1d-restricted T cells (NKT cells) to have unique effector functions without counterpart among MHC-restricted T cells. This review describes the function of CD1-restricted T cells in antimicrobial responses, antitumor immunity, and in regulating the balance between tolerance and autoimmunity.
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    Annual Review of Immunology 22 (2004), S. 683-709 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Human vascular endothelial cells (EC) basally display class I and II MHC-peptide complexes on their surface and come in regular contact with circulating T cells. We propose that EC present microbial antigens to memory T cells as a mechanism of immune surveillance. Activated T cells, in turn, provide both soluble and contact-dependant signals to modulate normal EC functions, including formation and remodeling of blood vessels, regulation of blood flow, regulation of blood fluidity, maintenance of permselectivity, recruitment of inflammatory leukocytes, and antigen presentation leading to activation of T cells. T cell interactions with vascular EC are thus bidirectional and link the immune and circulatory systems.
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    Annual Review of Immunology 22 (2004), S. 33-54 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Dendritic cells (DCs) are highly efficient antigen-presenting cells (APCs) that collect antigen in body tissues and transport them to draining lymph nodes. Antigenic peptides are loaded onto major histocompatibility complex (MHC) molecules for presentation to naive T cells, resulting in the induction of cellular and humoral immune responses. DCs take up antigen through phagocytosis, pinocytosis, and endocytosis via different groups of receptor families, such as Fc receptors for antigen-antibody complexes, C-type lectin receptors (CLRs) for glycoproteins, and pattern recognition receptors, such as Toll-like receptors (TLRs), for microbial antigens. Uptake of antigen by CLRs leads to presentation of antigens on MHC class I and II molecules. DCs are well equipped to distinguish between self- and nonself-antigens by the variable expression of cell-surface receptors such as CLRs and TLRs. In the steady state, DCs are not immunologically quiescent but use their antigen-handling capacities to maintain peripheral tolerance. DCs are continuously sampling and presenting self- and harmless environmental proteins to silence immune activation. Uptake of self-components in the intestine and airways are good examples of sites where continuous presentation of self- and foreign antigens occurs without immune activation. In contrast, efficient antigen-specific immune activation occurs upon encounter of DCs with nonself-pathogens. Recognition of pathogens by DCs triggers specific receptors such as TLRs that result in DC maturation and subsequently immune activation. Here we discuss the concept that cross talk between TLRs and CLRs, differentially expressed by subsets of DCs, accounts for the different pathways to peripheral tolerance, such as deletion and suppression, and immune activation.
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    Annual Review of Immunology 22 (2004), S. 1-31 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
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    Annual Review of Immunology 22 (2004), S. 891-928 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Chemokines compose a sophisticated communication system used by all our cell types, including immune cells. Chemokine messages are decoded by specific receptors that initiate signal transduction events leading to a multitude of cellular responses, leukocyte chemotaxis and adhesion in particular. Critical determinants of the in vivo activities of chemokines in the immune system include their presentation by endothelial cells and extracellular matrix molecules, as well as their cellular uptake via "silent" chemokine receptors (interceptors) leading either to their transcytosis or to degradation. These regulatory mechanisms of chemokine histotopography, as well as the promiscuous and overlapping receptor specificities of inflammation-induced chemokines, shape innate responses to infections and tissue damage. Conversely, the specific patterns of homeostatic chemokines, where each chemokine is perceived by a single receptor, are charting lymphocyte navigation routes for immune surveillance. This review presents our current understanding of the mechanisms that regulate the cellular perception and pathophysiologic meaning of chemokines.
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    Annual Review of Immunology 22 (2004), S. 711-743 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: The purpose of immunological memory is to protect the host from reinfection, to control persistent infections, and, through maternal antibody, to protect the host's immunologically immature offspring from primary infections. Immunological memory is an exclusive property of the acquired immune system, where in the presence of CD4 T cell help, T cells and B cells clonally expand and differentiate to provide effector systems that protect the host from pathogens. Here we describe how T and B cell memory is generated in response to virus infections and how these cells respond when the host is infected again by similar or different viruses.
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    Annual Review of Immunology 22 (2004), S. 81-127 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Ubiquitin (Ub)-protein conjugation represents a novel means of posttranscriptional modification in a proteolysis-dependent or -independent manner. E3 Ub ligases play a key role in governing the cascade of Ub transfer reactions by recognizing and catalyzing Ub conjugation to specific protein substrates. The E3s, which can be generally classified into HECT-type and RING-type families, are involved in the regulation of many aspects of the immune system, including the development, activation, and differentiation of lymphocytes, T cell-tolerance induction, antigen presentation, immune evasion, and virus budding. E3-promoted ubiquitination affects a wide array of biological processes, such as receptor downmodulation, signal transduction, protein processing or translocation, protein-protein interaction, and gene transcription, in addition to proteasome-mediated degradation. Deficiency or mutation of some of the E3s like Cbl, Cbl-b, or Itch, causes abnormal immune responses such as autoimmunity, malignancy, and inflammation. This review discusses our current understanding of E3 Ub ligases in both innate and adaptive immunity. Such knowledge may facilitate the development of novel therapeutic approaches for immunological diseases.
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    Annual Review of Immunology 22 (2004), S. 503-529 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Cytokines are an integral component of the adaptive and innate immune responses. The signaling pathways triggered by the engagement of cytokines with their specific cell surface receptors have been extensively studied and have provided a profound understanding of the intracellular machinery that translates exposure of cells to cytokine to a coordinated biological response. It has also become clear that cells have evolved sophisticated mechanisms to prevent excessive responses to cytokines. In this review we focus on the suppressors of cytokine signaling (SOCS) family of cytoplasmic proteins that completes a negative feedback loop to attenuate signal transduction from cytokines that act through the janus kinase/signal transducer and activator of transcription (JAK/STAT) pathway. SOCS proteins inhibit components of the cytokine signaling cascade via direct binding or by preventing access to the signaling complex. The SOCS proteins also appear to target signal transducers for proteasomal destruction. Analyses of genetically modified mice in which SOCS proteins are overexpressed or deleted have established that this family of negative regulators has indispensable roles in regulating cytokine responses in cells of the immune system as well as other tissues. Emerging evidence also suggests that disruption of SOCS expression or activity is associated with several immune and inflammatory diseases, raising the prospect that manipulation of SOCS activity may provide a novel future therapeutic strategy in the management of immunological disorders.
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    Annual Review of Immunology 22 (2004), S. 307-328 
    ISSN: 0732-0582
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Development of the acquired immune response is dependent on the signaling of CD40 by its ligand, CD154. These molecules govern both the magnitude and quality of humoral- and cell-mediated immunity. A litany of studies have conclusively documented that blockade of this ligand-receptor pair can prevent, and also intervene in, the progression of antibody- and cell-mediated autoimmune diseases, and can instill long-lived allogeneic and xenogeneic graft tolerance. Many effector mechanisms of inflammation are abolished as a result of CD154 blockade, but we are now beginning to understand that CD154 blockade may, in some instances, engender long-lived, antigen-specific tolerance. In the context of transplantation tolerance, we present a hypothesis that alphaCD154 blockade is most effective at inducing long-lived allospecific tolerance if anergy and regulation can be elicited prior to the onslaught of inflammation that is induced by grafting (preemptive tolerance). This facet of alphaCD154-induced tolerance appears to co-opt the normal processes of peripheral tolerance induced by immature DCs and can be exploited to induce long-lived antigen-specific tolerance. The underlying science and the prospects for inducing long-lived antigen-specific tolerance in a model of allograft tolerance through CD154 blockade are presented and discussed.
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Nucleation of microtubules by eukaryotic microtubule organizing centers (MTOCs) is required for a variety of functions, including chromosome segregation during mitosis and meiosis, cytokinesis, fertilization, cellular morphogenesis, cell motility, and intracellular trafficking. Analysis of MTOCs from different organisms shows that the structure of these organelles is widely varied even though they all share the function of microtubule nucleation. Despite their morphological diversity, many components and regulators of MTOCs, as well as principles in their assembly, seem to be conserved. This review focuses on one of the best-characterized MTOCs, the budding yeast spindle pole body (SPB). We review what is known about its structure, protein composition, duplication, regulation, and functions. In addition, we discuss how studies of the yeast SPB have aided investigation of other MTOCs, most notably the centrosome of animal cells.
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Gap junctions contain hydrophilic membrane channels that allow direct communication between neighboring cells through the diffusion of ions, metabolites, and small cell signaling molecules. They are made up of a hexameric array of polypeptides encoded by the connexin multi-gene family. Cell-cell communication mediated by connexins is crucial to various cellular functions, including the regulation of cell growth, differentiation, and development. Mutations in connexin genes have been linked to a variety of human diseases, including cardiovascular anomalies, peripheral neuropathy, deafness, skin disorders, and cataracts. In addition to their coupling function, recent studies suggest that connexin proteins may also mediate signaling. This could involve interactions with other protein partners that may play a role not only in connexin assembly, trafficking, gating and turnover, but also in the coordinate regulation of cell-cell communication with cell adhesion and cell motility. The integration of these cell functions is likely to be important in the role of gap junctions in development and disease.
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Clathrin-coated vesicles (CCVs) are responsible for the transport of proteins between various compartments of the secretory and endocytic systems. Clathrin forms a scaffold around these vesicles that is linked to membranes by clathrin adaptors. The adaptors simultaneously bind to clathrin and to transmembrane proteins and/or phospholipids and can also interact with each other and with other components of the CCV formation machinery. The result is a collection of proteins that can make multiple, moderate strength (M Kd) interactions and thereby establish the dynamic regulatable networks to drive vesicle genesis at the correct time and place in the cell. This review focuses on the structure of clathrin adaptors and how these structures provide functional information on the mechanism of CCV formation.
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Cell polarity, as reflected by polarized growth and organelle segregation during cell division in yeast, appears to follow a simple hierarchy. On the basis of physical cues from previous cell cycles or stochastic processes, yeast cells select a site for bud emergence that also defines the axis of cell division. Once polarity is established, rho protein-based signal pathways set up a polarized cytoskeleton by activating localized formins to nucleate and assemble polarized actin cables. These serve as tracks for the transport of secretory vesicles, the segregation of the trans Golgi network, the vacuole, peroxisomes, endoplasmic reticulum, mRNAs for cell fate determination, and microtubules that orient the nucleus in preparation for mitosis, all by myosin-Vs encoded by the MYO2 and MYO4 genes. Most of the proteins participating in these processes in yeast are conserved throughout the kingdoms of life, so the emerging models are likely to be generally applicable. Indeed, several parallels to cellular organization in animals are evident.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Programmed cell death involves the removal of cell corpses by other cells in a process termed engulfment. Genetic studies of the nematode Caenorhabditis elegans have led to a framework not only for the killing step of programmed cell death but also for the process of cell-corpse engulfment. This work has defined two signal transduction pathways that act redundantly to control engulfment. Signals expressed by dying cells probably regulate these C. elegans pathways. Components of the cell-corpse recognition system of one of the C. elegans pathways include the CED-7 ABC transporter, which likely presents a death ligand on the surface of the dying cell; the CED-1 transmembrane receptor, which recognizes this signal; and the CED-6 adaptor protein, which may transduce a signal from CED-1. The second C. elegans pathway acts in parallel and involves a novel Rac GTPase signaling pathway, with the components CED-2 CrkII, CED-5 DOCK180, CED-12 ELMO, and CED-10 Rac. The cell-corpse recognition system that activates this pathway remains to be characterized. In C. elegans, and possibly in mammals, the process of cell-corpse engulfment promotes the death process itself. The known mechanisms for cell-corpse engulfment leave much to be discovered concerning this fundamental aspect of metazoan biology.
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    ISSN: 1081-0706
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Medicine
    Notes: Significant advances have been made in the application of genetics to probe the functions of basement membrane laminins. These studies have shown that different laminin subunits profoundly affect tissue morphogenesis, starting around the time of embryonic implantation and extending through organogenesis and into the postnatal period. Collectively they have revealed common functions that include the induction and maintenance of cell polarity, the establishment of barriers between tissue compartments, the organization of cells into tissues, and the protection of adherent cells from detachment-induced cell death, anoikis. Interpreted in light of what is known about laminin structure and self-assembly and binding activities, these advances have begun to provide insights into mechanisms of action. In this review we focus on the contributions of the laminins in invertebrate and vertebrate tissue morphogenesis.
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    Annual Review of Materials Research 34 (2004), S. 339-372 
    ISSN: 1531-7331
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Mechanical Engineering, Materials Science, Production Engineering, Mining and Metallurgy, Traffic Engineering, Precision Mechanics
    Notes: Nanostructures are fabricated using either conventional or unconventional tools-that is, by techniques that are highly developed and widely used or by techniques that are relatively new and still being developed. This chapter reviews techniques of unconventional nanofabrication, and focuses on experimentally simple and inexpensive approaches to pattern features with dimensions 〈100 nm. The techniques discussed include soft lithography, scanning probe lithography, and edge lithography. The chapter includes recent advances in fabricating nanostructures using each set of techniques, together with demonstrated advantages, limitations, and applications for each.
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