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  • American Geophysical Union (AGU)  (37,460)
  • Annual Reviews
  • 2000-2004  (27,345)
  • 1980-1984  (14,156)
  • 1935-1939  (699)
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  • 1
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract We assess the environmental health impact and policy implications of the widespread addition of methyl tert-butyl ether (MTBE) as a chemical that is used as an oxygenate to much of the gasoline supply in the United States. Initial concerns about short-term and long-term adverse health consequences following the substantial increase in MTBE use in the winter of 1992-1993 have been supplemented by the discovery in 1996 of what is now relatively widespread contamination of groundwater. We identify 14 governmental initiatives during the 10-year period 1989-1999 in which the potential adverse consequences of MTBE were considered and a nearly identical research agenda was proposed. The lessons from the ongoing MTBE episode show that: (a) research should precede rather than follow environmental health policy decisions; (b) the extent of potential human and environmental exposure should be an important criterion in determining the amount of information needed before making an environmental policy decision; (c) a better understanding of nonspecific human symptoms associated with environmental exposures is needed; (d) the boundaries between the US Environmental Protection Agency program offices should be as porous as the boundaries between environmental media; (e) the US Environmental Protection Agency needs to focus more on public health rather than on legal approaches to environmental management; (f) it is more difficult to remove a chemical once it is in commerce than it is to prevent its use; (g) resolution of uncertainty is best accomplished through research rather than through repetitive review; and (h) better tools are needed to evaluate risk/risk trade-offs. The ongoing replacement of MTBE by other, less well studied oxygenates such as tertiary amyl methyl ether indicates that these environmental public policy lessons have not been learned.
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  • 2
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The interdependency of aircraft technological systems, the global reach of the aviation transport industry, and the uncertainty surrounding potential atmospheric effects have made defining the relationship between aviation and environmental impact an arduous task. Air travel continues to experience the fastest growth of all modes of transport, and although the energy intensity of the aviation transport system continues to decline, fuel use and total emissions have steadily risen. This trend, which represents a conflict between growth and environmental impact, has motivated the aircraft manufacturing and airline industries, the scientific community, and governmental bodies to consider what pace of emissions reduction is acceptable. This paper analyzes the historical influence of aircraft performance on cost to examine the potential pace of future efficiency improvements and emissions reduction. Technological and operational influences on aircraft energy intensity are quantified and correlated with direct operating cost and aircraft price using analytical and statistical models built upon historical data for US airlines. The energy intensity reduction potential and economic characteristics of future aircraft are also projected, through extrapolations of historical trends in aircraft technology and operations.
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  • 3
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Over the past 20 years, a new scientific discipline based on direct measurement of human exposure to environmental pollutants has developed. The fundamental principle of the new science is to "measure where the people are." This has required developing small, lightweight, quiet personal monitors for volatile organic compounds and other pollutants. A second principle has been to measure body burden, particularly exhaled breath, whenever possible to determine the relationship between exposure and dose. Studies employing the new monitors and breath measurements have overturned accepted ideas about the sources of most volatile organic pollutants. The main sources turn out surprisingly often to be small, close to the person, and completely unregulated. These findings should result in major changes in our approach to environmental regulation; however, powerful forces of resistance would need to be overcome.
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  • 4
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Civilization's advances during the twentieth century are closely bound with an unprecedented rise of energy consumption in general, and of hydrocarbons and electricity in particular. Substantial improvements of all key nineteenth-century energy techniques and introduction of new extraction and transportation means and new prime movers resulted in widespread diffusion of labor-saving and comfort-providing conversions and in substantially declining energy prices. Although modern societies could not exist without large and incessant flows of energy, there are no simple linear relationships between the inputs of fossil fuels and electricity and a nation's economic performance and social accomplishments. International comparisons show a variety of consumption patterns and a continuing large disparity between affluent and modernizing nations. The necessity of minimizing environmental impacts of energy use, particularly those with potentially worrisome global effects, is perhaps the greatest challenge resulting from the twentieth century's energy advances.
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  • 5
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Theoretical considerations and empirical data suggest that existing technologies and procedures can improve indoor environments in a manner that significantly increases productivity and health. The existing literature contains moderate to strong evidence that characteristics of buildings and indoor environments significantly influence rates of communicable respiratory illness, allergy and asthma symptoms, sick building symptoms, and worker performance. Whereas there is considerable uncertainty in the estimates of the magnitudes of productivity gains that may be obtained by providing better indoor environments, the projected gains are very large. For the United States, the estimated potential annual savings and productivity gains are $6 to $14 billion from reduced respiratory disease, $1 to $4 billion from reduced allergies and asthma, $10 to $30 billion from reduced sick building syndrome symptoms, and $20 to $160 billion from direct improvements in worker performance that are unrelated to health. Productivity gains that are quantified and demonstrated could serve as a strong stimulus for energy efficiency measures that simultaneously improve the indoor environment.
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  • 6
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Low environmental damage is one of the main justifications for continued efforts to reduce energy consumption and to shift to cleaner sources such as solar energy, especially now that supply security has slipped from public consciousness. In recent years there has been much progress in the analysis of environmental damages, in particular thanks to the ExternE (External Costs of Energy) Project of the European Commission. This paper presents a summary of the methodology and key results for the external costs of the major energy technologies. Even though the uncertainties are large, the results provide substantial evidence that the classic air pollutants (particles, NOx and SOx) from fossil fuels impose significant public health costs, comparable to the cost of global warming from CO2 emissions.
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  • 7
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: The evolution from an electrochemist was motivated by a growing conviction that Indian science and technology should be reoriented. A cell was created in the Indian Institute of Science in 1974 to initiate and promote work of rural relevance as a weapon against poverty. Surveys led to a detailed empirical study of energy consumption patterns in villages and to the design and construction of rural energy centers. The lessons from this village work are described. The principal outcome of the collaboration with J. Goldemberg (Brazil), T.B. Johansson (Sweden), and R.H. Williams (United States) was the book Energy for a Sustainable World that contributed significantly to the new paradigm for energy. The application of this paradigm resulted in a detailed electricity demand scenario for the South Indian state of Karnataka. Following mandatory retirement from the Indian Institute of Science, the International Energy Initiative (IEI) was set up in 1991 as a Southern-conceived, Southern-led, Southern-located South-North partnership. Persisting personal concerns about the ethical implications of science resurfaced through opposition to India's nuclear tests in 1998 and a visit to the concentration camps at Auschwitz. The associated human dimensions of energy were emphasized in the acceptance speech at Goteborg of the Volvo Environment Prize 2000. The penultimate endgame involved retirement.
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  • 8
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract From modest beginnings in the 1960s, environmental economics has grown to be a major subdiscipline of economics. It combines traditional work in the field of welfare economics and the theory of economic growth with more recent perspectives on the political economy of choosing policy instruments and the philosophy of sustainable development. The central tenets are that environmental problems have their roots in the failure of economic systems to maximize human well-being, that environmental quality matters for human well-being and for more traditionally oriented economic growth objectives, and that efficient policy can be achieved through incentive design.
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  • 9
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Students of public policy sometimes envision an idealized policy process where competent data collection and incisive analysis on both sides of a debate lead to reasoned judgments and sound decisions. Unfortunately, numbers that prove decisive in policy debates are not always carefully developed, credibly documented, or correct. This paper presents four widely cited examples of numbers in the energy field that are either misleading or wrong. It explores the origins of these numbers, how they missed the mark, and how they have been misused by both analysts and the media. In addition, it describes and uses a three-stage analytical process for evaluating such statistics that involves defining terms and boundaries, assessing underlying data, and critically analyzing arguments.
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  • 10
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Fossil fuels play a crucial role in satisfying growing world energy demands, but their continued use could cause irreparable harm to the environment. Unless virtually all anthropogenic carbon dioxide is captured, either at the source or subsequently from the air, and disposed of safely and permanently, fossil fuels may have to be phased out over the next few decades. Sequestration of waste carbon dioxide will require methods that can safely store several trillion tons of carbon dioxide. Long-term storage of a gaseous substance is fraught with uncertainty and hazards, but carbonate chemistry offers permanent solutions to the disposal problem. Carbonates can be formed from carbon dioxide and metal oxides in reactions that are thermodynamically favored and exothermic, which result in materials that can be safely and permanently kept out of the active carbon stocks in the environment. Carbonate sequestration methods require the development of an extractive minerals industry that provides the base ions for neutralizing carbonic acid.
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  • 11
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract Technical change in the energy sector is central for addressing long-term environmental issues, including climate change. Most models of energy, economy, and the environment (E3 models) use exogenous assumptions for this. This is an important weakness. We show that there is strong evidence that technical change in the energy sector is to an important degree induced by market circumstances and expectations and, by implication, by environmental policies such as CO2 abatement. We classify the main approaches to modeling such induced technical change and review results with particular reference to climate change. Among models with learning by doing, weak responses are only obtained from models that are highly aggregated (lack technological diversity) and/or that equate rates of return to innovation across sectors. Induced technical change broadens the scope of efficient policies toward mitigation, including not just research and development and aggregated market instruments but a range of sectoral-based policies potentially at divergent marginal costs. Furthermore, to the extent that cleaner technologies induced by mitigation diffuse globally, a positive spillover will result that will tend to offset the substitution-based negative spillover usually hypothesized to result from the migration of polluting industries. Initial explorations suggest that this effect could also be very large.
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  • 12
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract The cement industry contributes about 5% to global anthropogenic CO2 emissions, making the cement industry an important sector for CO2-emission mitigation strategies. CO2 is emitted from the calcination process of limestone, from combustion of fuels in the kiln, as well as from power generation. In this paper, we review the total CO2 emissions from cement making, including process and energy-related emissions. Currently, most available data only includes the process emissions. We also discuss CO2 emission mitigation options for the cement industry. Estimated total carbon emissions from cement production in 1994 were 307 million metric tons of carbon (MtC), 160 MtC from process carbon emissions, and 147 MtC from energy use. Overall, the top 10 cement-producing countries in 1994 accounted for 63% of global carbon emissions from cement production. The average intensity of carbon dioxide emissions from total global cement production is 222 kg of C/t of cement. Emission mitigation options include energy efficiency improvement, new processes, a shift to low carbon fuels, application of waste fuels, increased use of additives in cement making, and, eventually, alternative cements and CO2 removal from flue gases in clinker kilns.
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  • 13
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract During the period 1995-1999, the President's Committee of Advisors on Science and Technology (PCAST) produced three major energy studies, at President Clinton's request. The panels that conducted these studies were broadly constituted from the academic, industrial, and NGO (nongovernmental organization) sectors, and their recommendations were unanimous. These efforts (a) helped lay the foundation for several major energy initiatives of the second Clinton term, including the Climate Change Technology Initiative, the Nuclear Energy Research Initiative, and the International Clean Energy Initiative; (b) helped launch energy R&D activities on methane hydrates and geological sequestration of carbon dioxide; and (c) strengthened related activities, such as the Partnership for a New Generation of Vehicles, the Partnership for Advancing Technologies in Housing, the fossil power Vision-21 Program, and the National Bioenergy Initiative. Federal budgets for research, development, demonstration, and deployment of advanced energy technologies have increased substantially over the past four years, but they still fall short of PCAST's recommendations; and a number of the PCAST recommendations on matters other than budget have yet to be fully implemented. The PCAST energy studies demonstrate the possibility of forging consensus around key energy issues and provide a foundation on which, it is hoped, the continuing pursuit of a coherent national policy on energy innovation will be able to build.
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  • 14
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: FAUST: Ich fuhl's, vergebens hab' ich alle Schatze Des Menschengeists auf mich herbeigerafft, Und wenn ich mich am Ende niedersetze, Quilt innerlich doch keine neue Kraft; Ich bin nicht um ein Haar breit hoher, Bin dem Unendlichen nicht naher. Goethe's Faust, Part I, lines 1810-15. 1 A dedication to research in the physical sciences together with the circumstances of World War II, led me into theoretical and observational studies of the global physical climate. For all practical purposes, I was on my own when working in Cambridge and London, England, and I went whereever my interests led me. I organized three atmospheric observatories (two in England). I have also worked at many astronomical observatories. As time progressed, I became increasingly involved in studies of atmospheric radiation as a controlling factor for the Earth's climate. I am often taken to be a specialist in atmospheric radiation, but I have never regarded it as more than an important element in climate studies. But radiative transfer and global questions did not become important for climate science until later, and in the 1950s and 1960s I found myself drawn to studies of planetary atmospheres as an arena in which my skills were of central importance. Mars and Venus were the focus of my work for many years, and I was partly responsible for launching the Pioneer Venus mission, which placed probes into the Venus atmosphere in 1978. Much later, the experience I gained in space instrumentation and in the structure of atmospheres led me back to climate science, where I started. Then my interest was in observing the climate and testing the credibility of climate predictions. I still maintain some activity in this field. Outside these research activities, I created a Center for Earth and Planetary Physics at Harvard University to take over the activities of the Blue Hill Observatory, when that Observatory ceased to be a viable facility. The purpose of the Center was to teach earth science in the context of the discipline of physical science. The Center had some notable achievements but eventually had to give way to requirements for environmental sciences in the University, a change that I regret. During my active life in the United States, I invested a great deal of effort in support of the work of the National Research Council (NRC), including many years spent on report review. I am increasingly troubled by the postmodern view of science that appears to dominate these activities. But that may be no more than a biased rosy view of the past with its exciting early experiences and hopes.
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  • 15
    ISSN: 1056-3466
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Energy, Environment Protection, Nuclear Power Engineering
    Notes: Abstract This paper explores how long-term energy forecasts are created and why they are useful. It focuses on forecasts of energy use in the United States for the year 2000 but considers only long-term predictions, i.e., those covering two or more decades. The motivation is current interest in global warming forecasts, some of which run beyond a century. The basic observation is that forecasters in the 1950-1980 period underestimated the importance of unmodeled surprises. A key example is the failure to foresee the ability of the United States economy to respond to the oil embargos of the 1970s by increasing efficiency. Not only were most forecasts of that period systematically high, but forecasters systematically underestimated uncertainties. Long-term energy forecasts must make assumptions about both technologies and social systems. At their most successful, they influence how people act by showing the consequences of not acting. They are useful when they provide insights to energy planners, influence the perceptions of the public and the energy policy community, capture current understanding of underlying physical and economic principles, or highlight key emerging social or economic trends. It is true that at best we see dimly into the future, but those who acknowledge their duty to posterity will feel impelled to use their foresight upon what facts and guiding principles we do possess. Though many data are at present wanting or doubtful, our conclusions may be rendered so far probable as to lead to further inquiries... (1), p. 4.
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  • 16
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract A fundamental perspective can be achieved by targeting single cells for analysis with the goal of deconvoluting complex biological functions. However, single-cell studies have their own difficulties, such as minute volumes and sample amounts. Quantitative chemical analysis of single cells has emerged as a powerful new area in recent years due to several technological advancements. The development of microelectrodes has allowed the measurement of redox-active species as a function of cellular dynamics. This miniaturization trend is also evident in the separation sciences with the application of small column separations to single cells. Desorption ionization methods with mass spectrometric detection have shown single-cell capability owing to numerous technological developments. Finally, fluorescence imaging has also progressed to the point where single-cell dynamics can be probed by native fluorescence utilizing either single or multiple photon excitation. The results of these studies are reviewed with an emphasis on the quantitation of single-cell dynamics.
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  • 17
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Species and tissue-specific isozymes of phosphorylase display differences in regulatory properties consistent with their distinct roles in particular organisms and tissues. In this review, we compare crystallographic structures of regulated and unregulated phosphorylases, including maltodextrin phosphorylase (MalP) from Escherichia coli, glycogen phosphorylase from yeast, and mammalian isozymes from muscle and liver tissues. Mutagenesis and functional studies supplement the structural work and provide insights into the structural basis for allosteric control mechanisms. MalP, a simple, unregulated enzyme, is contrasted with the more complicated yeast and mammalian phosphorylases that have evolved regulatory sites onto the basic catalytic architecture. The human liver and muscle isozymes show differences structurally in their means of invoking allosteric activation. Phosphorylation, though common to both the yeast and mammalian enzymes, occurs at different sites and activates the enzymes by surprisingly different mechanisms.
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  • 18
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    Palo Alto, Calif. : Annual Reviews
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Atomic resolution structure determinations of proteins by X-ray crystallography are formidable multidisciplinary undertakings, requiring protein construct design, expression and purification, crystallization trials, phase determination, and model building. Modern mass spectrometric methods can greatly facilitate these obligate tasks. Thus, mass spectrometry can be used to verify that the desired protein construct has been correctly expressed, to define compact domains in the target protein, to assess the components contained within the protein crystals, and to screen for successful incorporation of seleno-methionine and other heavy metal reagents used for phasing. In addition, mass spectrometry can be used to address issues of modeling, topology, and side-chain proximity. Here, we demonstrate how rational use of mass spectrometry assists and expedites high resolution X-ray structure determination through each stage of the process of protein crystallography.
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  • 19
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Proteins are designed to function in environments crowded by cosolutes, but most studies of protein equilibria are conducted in dilute solution. While there is no doubt that crowding changes protein equilibria, interpretations of the changes remain controversial. This review combines experimental observations on the effect of small uncharged cosolutes (mostly sugars) on protein stability with a discussion of the thermodynamics of cosolute-induced nonideality and critical assessments of the most commonly applied interpretations. Despite the controversy surrounding the most appropriate manner for interpreting these effects of thermodynamic nonideality arising from the presence of small cosolutes, experimental advantage may still be taken of the ability of the cosolute effect to promote not only protein stabilization but also protein self-association and complex formation between dissimilar reactants. This phenomenon clearly has potential ramifications in the cell, where the crowded environment could well induce the same effects.
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  • 20
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The mammalian thioredoxins are a family of small (approximately 12 kDa) redox proteins that undergo NADPH-dependent reduction by thioredoxin reductase and in turn reduce oxidized cysteine groups on proteins. The two main thioredoxins are thioredoxin-1, a cytosolic and nuclear form, and thioredoxin-2, a mitochondrial form. Thioredoxin-1 has been studied more. It performs many biological actions including the supply of reducing equivalents to thioredoxin peroxidases and ribonucleotide reductase, the regulation of transcription factor activity, and the regulation of enzyme activity by heterodimer formation. Thioredoxin-1 stimulates cell growth and is an inhibitor of apoptosis. Thioredoxins may play a role in a variety of human diseases including cancer. An increased level of thioredoxin-1 is found in many human tumors, where it is associated with aggressive tumor growth. Drugs are being developed that inhibit thioredoxin and that have antitumor activity.
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  • 21
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
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  • 22
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The first crystal structures of intact T cell receptors (TCRs) bound to class I peptide-MHC (pMHCs) antigens were determined in 1996. Since then, further structures of class I TCR/pMHC complexes have explored the degree of structural variability in the TCR-pMHC system and the structural basis for positive and negative selection. The recent determination of class II and allogeneic class I TCR/pMHC structures, as well as those of accessory molecules (e.g., CD3), has pushed our knowledge of TCR/pMHC interactions into new realms, shedding light on clinical pathologies, such as graft rejection and graft-versus-host disease. Furthermore, the determination of coreceptor structures lays the foundation for a more comprehensive structural description of the supramolecular TCR signaling events and those assemblies that arise in the immunological synapse. While these telling photodocumentaries of the TCR/pMHC interaction are composed mainly from static crystal structures, a full description of the biological snapshots in T cell signaling requires additional analytical methods that record the dynamics of the process. To this end, surface plasmon resonance (SPR), isothermal titration calorimetry (ITC), and ultracentrifugation (UC) have furnished both affinities and kinetics of the TCR/pMHC association. In the past year, structural, biochemical, and molecular biological data describing TCR/pMHC interactions have sublimely coalesced into a burgeoning well of understanding that promises to deliver further insights into T cell recognition. The coming years will, through a more intimate union of structural and kinetic data, allow many pressing questions to be addressed, such as how TCR/pMHC ligation is affected by coreceptor binding and what is the mechanism of TCR signaling in both early and late stages of T cell engagement with antigen-presenting cells.
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  • 23
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract During the course of their biological function, proteins undergo different types of structural rearrangements ranging from local to large-scale conformational changes. These changes are usually triggered by their interactions with small-molecular-weight ligands or other macromolecules. Because binding interactions occur at specific sites and involve only a small number of residues, a chain of cooperative interactions is necessary for the propagation of binding signals to distal locations within the protein structure. This process requires an uneven structural distribution of protein stability and cooperativity as revealed by NMR-detected hydrogen/deuterium exchange experiments under native conditions. The distribution of stabilizing interactions does not only provide the architectural foundation to the three-dimensional structure of a protein, but it also provides the required framework for functional cooperativity. In this review, the statistical thermodynamic linkage between protein stability, functional cooperativity, and ligand binding is discussed.
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  • 24
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The field of computational cell biology has emerged within the past 5 years because of the need to apply disciplined computational approaches to build and test complex hypotheses on the interacting structural, physical, and chemical features that underlie intracellular processes. To meet this need, newly developed software tools allow cell biologists and biophysicists to build models and generate simulations from them. The construction of general-purpose computational approaches is especially challenging if the spatial complexity of cellular systems is to be explicitly treated. This review surveys some of the existing efforts in this field with special emphasis on a system being developed in the authors' laboratory, Virtual Cell. The theories behind both stochastic and deterministic simulations are discussed. Examples of respective applications to cell biological problems in RNA trafficking and neuronal calcium dynamics are provided to illustrate these ideas.
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  • 25
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    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract Structural and thermodynamic characterizations of a variety of intra- and intermolecular interactions stabilizing/destabilizing protein systems represent a major part of multidisciplinary efforts aimed at solving the problems of protein folding and binding. To this end, volumetric techniques have been successfully used to gain insights into protein hydration and intraglobular packing. Despite the fact that the use of volumetric measurements in protein-related studies dates back to the 1950s, such measurements still represent a relatively untapped yet potentially informative means for tackling the problems of protein folding and binding. This notion has been further emphasized by recent advances in the development of highly sensitive volumetric instrumentation that has led to intensifying volumetric investigations of protein systems. This paper reviews the volumetric properties of proteins and their low-molecular-weight analogs, in particular, discussing the recent progress in the use of volumetric data for studying conformational transitions of proteins as well as protein-ligand, protein-protein, and protein-nucleic acid interactions.
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  • 26
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract This review focuses on cofactor-ligand and protein-protein interactions within the photosystem I reaction center. The topics include a description of the electron transfer cofactors, the mode of binding of the cofactors to protein-bound ligands, and a description of intraprotein contacts that ultimately allow photosystem I to be assembled (in cyanobacteria) from 96 chlorophylls, 22 carotenoids, 2 phylloquinones, 3 [4Fe-4S] clusters, and 12 polypeptides. During the 15 years that have elapsed from the first report of crystals to the atomic-resolution X-ray crystal structure, cofactor-ligand interactions and protein-protein interactions were systematically being explored by spectroscopic and genetic methods. This article charts the interplay between these disciplines and assesses how good the early insights were in light of the current structure of photosystem I.
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  • 27
    ISSN: 1056-8700
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology , Physics
    Notes: Abstract The past decade has witnessed increasingly detailed insights into the structural mechanism of the bacteriorhodopsin photocycle. Concurrently, there has been much progress within our knowledge pertaining to the lipids of the purple membrane, including the discovery of new lipids and the overall effort to localize and identify each lipid within the purple membrane. Therefore, there is a need to classify this information to generalize the findings. We discuss the properties and roles of haloarchaeal lipids and present the structural data as individual case studies. Lipid-protein interactions are discussed in the context of structure-function relationships. A brief discussion of the possibility that bacteriorhodopsin functions as a light-driven inward hydroxide pump rather than an outward proton pump is also presented.
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  • 28
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    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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    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Hydrogels are cross-linked hydrophilic polymers that can imbibe water or biological fluids. Their biomedical and pharmaceutical applications include a very wide range of systems and processes that utilize several molecular design characteristics. This review discusses the molecular structure, dynamic behavior, and structural modifications of hydrogels as well as the various applications of these biohydrogels. Recent advances in the preparation of three-dimensional structures with exact chain conformations, as well as tethering of functional groups, allow for the preparation of promising new hydrogels. Meanwhile, intelligent biohydrogels with pH- or temperature-sensitivity continue to be important materials in medical applications.
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  • 30
    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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  • 31
    ISSN: 1056-8700
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    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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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Two-dimensional viewing of three-dimensional anatomy by conventional ultrasound limits our ability to quantify and visualize a number of diseases and is partly responsible for the reported variability in diagnosis. Over the past two decades, many investigators have addressed this limitation by developing three-dimensional imaging techniques, including three-dimensional ultrasound imaging. In this paper we describe the development of a number of three-dimensional ultrasound imaging systems that make use of B mode, color Doppler, and power Doppler. In these systems, the conventional ultrasound transducer is scanned mechanically or by a freehand technique. The ultrasound images are digitized and then reconstructed into a three-dimensional volume, which can be viewed and manipulated interactively by the diagnostician with a variety of image-rendering techniques. These developments as well as future trends are discussed with regard to their applications and limitations.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Electrical shock trauma tends to produce a very complex pattern of injury, mainly because of the multiple modes of frequency-dependent tissue-field interactions. Historically, Joule heating was thought to be the only cause of electrical injuries to tissue by commercial-frequency electrical shocks. In the last 15 years, biomedical engineering research has improved the understanding of the underlying biophysical injury mechanisms. Besides thermal burns secondary to Joule heating, permeabilization of cell membranes and direct electroconformational denaturation of macromolecules such as proteins have also been identified as tissue-damage mechanisms. This review summarizes the physics of tissue injury caused by contact with commercial-frequency power lines, as well as exposure to lightning and radio frequency (RF), microwave, and ionizing radiation. In addition, we describe the anatomic patterns of the resultant tissue injury from these modes of electromagnetic exposures.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract We review some of the most recent advances in the area of wavelet applications in medical imaging. We first review key concepts in the processing of medical images with wavelet transforms and multiscale analysis, including time-frequency tiling, overcomplete representations, higher dimensional bases, symmetry, boundary effects, translational invariance, orientation selectivity, and best-basis selection. We next describe some applications in magnetic resonance imaging, including activation detection and denoising of functional magnetic resonance imaging and encoding schemes. We then present an overview in the area of ultrasound, including computational anatomy with three-dimensional cardiac ultrasound. Next, wavelets in tomography are reviewed, including their relationship to the radon transform and applications in position emission tomography imaging. Finally, wavelet applications in digital mammography are reviewed, including computer-assisted diagnostic systems that support the detection and classification of small masses and methods of contrast enhancement.
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  • 35
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The goal of the Image Guided Therapy Program, as the name implies, is to develop the use of imaging to guide minimally invasive therapy. The program combines interventional and intraoperative magnetic resonance imaging (MRI) with high-performance computing and novel therapeutic devices. In clinical practice the multidisciplinary program provides for the investigation of a wide range of interventional and surgical procedures. The Signa SP 0.5 T superconducting MRI system (GE Medical Systems, Milwaukee, WI) has a 56-cm-wide vertical gap, allowing access to the patient and permitting the execution of interactive MRI-guided procedures. This system is integrated with an optical tracking system and utilizes flexible surface coils and MRI-compatible displays to facilitate procedures. Images are obtained with routine pulse sequences. Nearly real-time imaging, with fast gradient-recalled echo sequences, may be acquired at a rate of one image every 1.5 s with interactive image plane selection. Since 1994, more than 800 of these procedures, including various percutaneous procedures and open surgeries, have been successfully performed at Brigham and Women's Hospital (Boston, MA).
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Interrogation of tissue with light offers the potential for noninvasive chemical measurement, and penetration with near-infrared wavelengths (750-1000 nm) is greater than with visible light. Specific absorption by clinically relevant compounds such as oxy- and deoxyhemoglobin and the intracellular respiratory enzyme cytochrome oxidase enable in vivo measurement of these to be performed safely and conveniently. This is the basis of in vivo near-infrared spectroscopy (ivNIRS). Multiple scattering of the interrogating beam by tissues leads to an optical path that is considerably longer than the simple physical pathlength and this complicates the analysis. Modeling of photon propagation through tissues with, for example, finite element and Monte Carlo methods, is assisting in improving the ivNIRS methodology. Instrumentation has advanced from simple continuous wave approaches, through time-resolved methods based on either time-domain or frequency-domain approaches, to spatially resolved measurement based on diffuse reflectance. Initial clinical applications were for monitoring the brain in the neonate and fetus and muscle in adults. Currently, use in adults and children for neurological assessments are of growing interest.
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  • 37
    ISSN: 1523-9829
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Recent studies suggest that there are multiple regulatory pathways by which chondrocytes in articular cartilage sense and respond to mechanical stimuli, including upstream signaling pathways and mechanisms that may lead to direct changes at the level of transcription, translation, post-translational modifications, and cell-mediated extracellular assembly and degradation of the tissue matrix. This review focuses on the effects of mechanical loading on cartilage and the resulting chondrocyte-mediated biosynthesis, remodeling, degradation, and repair of this tissue. The effects of compression and tissue shear deformation are compared, and approaches to the study of mechanical regulation of gene expression are described. Of particular interest regarding dense connective tissues, recent experiments have shown that mechanotransduction is critically important in vivo in the cell-mediated feedback between physical stimuli, the molecular structure of newly synthesized matrix molecules, and the resulting macroscopic biomechanical properties of the tissue.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Thomas A. McMahon (1943-1999) was a pioneer in the field of biomechanics. He made primary contributions to our understanding of terrestrial locomotion, allometry and scaling, cardiac assist devices, orthopedic biomechanics, and a number of other areas. His work was frequently characterized by the use of simple mathematical models to explain seemingly complex phenomena. He also validated these models through creative experimentation. McMahon was a successful inventor and also published three well-received novels. He was raised in Lexington, Massachussetts, attended Cornell University as an undergraduate, and earned a PhD at MIT. From 1970 until his death, he was a member of the faculty of Harvard University, where he taught biomedical engineering. He is fondly remembered as a warm and gentle colleague and an exemplary mentor to his students.
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    Notes: Abstract It long has been known that mechanical forces play a role in the development of the cardiovascular system, but only recently have biomechanical engineers begun to explore this field. This paper reviews some of this work. First, an overview of the relevant biology is discussed. Next, a mechanical theory is presented that can be used to model developmental processes. The theory includes the effects of finite volumetric growth and active contractile forces. Finally, applications of this and other theories to problems of cardiovascular development are discussed, and some future directions are suggested. The intent is to stimulate further interest among engineers in this important area of research.
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    Notes: Abstract Medical imaging has been used primarily for diagnosis. In the past 15 years there has been an emergence of the use of images for the guidance of therapy. This process requires three-dimensional localization devices, the ability to register medical images to physical space, and the ability to display position and trajectory on those images. This paper examines the development and state of the art in those processes.
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  • 41
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract This is the second of two chapters (the first chapter appeared in the Annual Review of Biomedical Engineering, 2000, 2:55-81) dealing with some 60 years of accumulated knowledge in the field of impact biomechanics. The regions covered in the first chapter were the head, neck, and thorax. In this chapter, the abdomen, pelvis, and lower extremities are discussed. The thoracolumbar spine is not covered because of length limitations and the low frequency of injury to this area from automotive accidents. Again, in the cited results, the reader needs to be keenly aware of the wide variation in human response and tolerance. This is due primarily to the large biological variations among humans and to the effects of aging. Average values that are useful in design cannot be applied to individuals.
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    Notes: Abstract The heart requires a large amount of energy to sustain both ionic homeostasis and contraction. Under normal conditions, adenosine triphosphate (ATP) production meets this demand. Hence, there is a complex regulatory system that adjusts energy production to meet this demand. However, the mechanisms for this control are a topic of active debate. Energy metabolism can be divided into three main stages: substrate delivery to the tricarboxylic acid (TCA) cycle, the TCA cycle, and oxidative phosphorylation. Each of these processes has multiple control points and exerts control over the other stages. This review discusses the basic stages of energy metabolism, mechanisms of control, and the mathematical and computational models that have been used to study these mechanisms.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The development of man-made systems to restore functional vision in the profoundly blind has recently undergone a renaissance that has been fueled by a combination of celebrity and government interest, advances in the field of bioengineering, and successes with existing neuroprosthetic systems. This chapter presents the underlying physiologic principles of artificial vision, discusses three contemporary approaches to restoring functional vision in the blind, and concludes by presenting several relevant questions to vision prostheses. While there has been significant progress in the individual components constituting an artificial vision system, the remaining challenge of integrating these components with each other and the nervous system does not lie strictly in the realm of neuroscience, medicine, or engineering but at the interface of all three. In spite of the apparent complexity of an artificial vision system, it is not unreasonable to be optimistic about its eventual success.
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    Notes: Abstract The Human Genome Project and other major genomic sequencing projects have pushed the development of sequencing technology. In the past six years alone, instrument throughput has increased 15-fold. New technologies are now on the horizon that could yield massive increases in our capacity for de novo DNA sequencing. This review presents a summary of state-of-the-art technologies for genomic sequencing and describes technologies that may be candidates for the next generation of DNA sequencing instruments.
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  • 45
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    Notes: Abstract Outer hair cell electromotility is crucial for the amplification, sharp frequency selectivity, and nonlinearities of the mammalian cochlea. Current modeling efforts based on morphological, physiological, and biophysical observations reveal transmembrane potential gradients and membrane tension as key independent variables controlling the passive and active mechanics of the cell. The cell's mechanics has been modeled on the microscale using a continuum approach formulated in terms of effective (cellular level) mechanical and electric properties. Another modeling approach is nanostructural and is based on the molecular organization of the cell's membranes and cytoskeleton. It considers interactions between the components of the composite cell wall and the molecular elements within each of its components. The methods and techniques utilized to increase our understanding of the central role outer hair cell mechanics plays in hearing are also relevant to broader research questions in cell mechanics, cell motility, and cell transduction.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract Recent interest in using modeling and simulation to study movement is driven by the belief that this approach can provide insight into how the nervous system and muscles interact to produce coordinated motion of the body parts. With the computational resources available today, large-scale models of the body can be used to produce realistic simulations of movement that are an order of magnitude more complex than those produced just 10 years ago. This chapter reviews how the structure of the neuromusculoskeletal system is commonly represented in a multijoint model of movement, how modeling may be combined with optimization theory to simulate the dynamics of a motor task, and how model output can be analyzed to describe and explain muscle function. Some results obtained from simulations of jumping, pedaling, and walking are also reviewed to illustrate the approach.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
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    Notes: Abstract The potential role of therapeutic ultrasound in medicine is promising. Currently, medical devices are being developed that utilize high-intensity focused ultrasound as a noninvasive method to treat tumors and to stop bleeding (hemostasis). The primary advantage of ultrasound that lends the technique so readily to use in noninvasive therapy is its ability to penetrate deep into the body and deliver to a specific site thermal or mechanical energy with submillimeter accuracy. Realizing the full potential of acoustic therapy, however, requires precise targeting and monitoring. Fortunately, several imaging modalities can be utilized for this purpose, thus leading to the concept of image-guided acoustic therapy. This article presents a review of high-intensity focused ultrasound therapy, including its mechanisms of action, the imaging modalities used for guidance and monitoring, some current applications, and the requirements and technology associated with this exciting and promising field.
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  • 49
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    Notes: Abstract Education in biomedical engineering offers a number of challenges to all constituents of the educational process-faculty, students, and employers of graduates. Although biomedical engineering educational systems have been under development for 40 years, interest in and the pace of development of these programs has accelerated in recent years. New advances in the learning sciences have provided a framework for the reexamination of instructional paradigms in biomedical engineering. This work shows that learning environments should be learner centered, knowledge centered, assessment centered, and community centered. In addition, learning technologies offer the potential to achieve this environment with efficiency. Biomedical engineering educators are in a position to design and implement new learning systems that can take advantage of advances in learning science, learning technology, and reform in engineering education.
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    Notes: Abstract Magnetic resonance imaging (MRI) is widely applied for functional imaging of the microcirculation and for functional and structural studies of the microvasculature. The interest in the capabilities of MRI in noninvasively monitoring changes in vascular structure and function expanded over the past years, with specific efforts directed toward the development of novel imaging methods for quantification of angiogenesis. Molecular imaging approaches hold promise for further expansion of the ability to characterize the microvasculature. Exciting applications for MRI are emerging in the study of the biology of microvessels and in the evaluation of potential pharmaceutical modulators of vascular function and development, and preclinical MRI tools can serve for the design of mechanism-of-action-based noninvasive clinical methods for monitoring response to therapy. The aim of this review is to provide a current snapshot of recent developments in this rapidly evolving field.
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    Notes: Abstract Computational models of the electrical and mechanical function of the heart are reviewed. These models attempt to explain the integrated function of the heart in terms of ventricular anatomy, the structure and material properties of myocardial tissue, the membrane ion channels, and calcium handling and myofilament mechanics of cardiac myocytes. The models have established the computational framework for linking the structure and function of cardiac cells and tissue to the integrated behavior of the intact heart, but many more aspects of physiological function, including metabolic and signal transduction pathways, need to be included before significant progress can be made in understanding many disease processes.
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    Notes: Abstract Advances in chemistry and physics are providing an expanding array of nanostructured materials with unique and powerful optical properties. These nanomaterials provide a new set of tools that are available to biomedical engineers, biologists, and medical scientists who seek new tools as biosensors and probes of biological fluids, cells, and tissue chemistry and function. Nanomaterials are also being used to develop optically controlled devices for applications such as modulated drug delivery as well as optical therapeutics. This review discusses applications that have been successfully demonstrated using nanomaterials including semiconductor nanocrystals, gold nanoparticles, gold nanoshells, and silver plasmon resonant particles.
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    Notes: Time reversal is a very powerful method for focusing through complex and heterogeneous media and shows very promising results in biomedical applications. In this paper, we review some of the main applications investigated during the past decade. An iterative implementation of the time-reversal process allows tracking gallstones in real time during lithotripsy treatments. In this application domain, a smart exploitation of the reverberations in solid waveguides permits the focusing of high-amplitude ultrasonic shock waves with a small number of transducers. Finally, because time reversal is able to correct the strong distortions induced by the skull bone on ultrasonic propagation, this adaptive focusing technique is very promising for ultrasonic hyperthermia brain therapy.
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    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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    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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    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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    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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    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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    ISSN: 1527-8204
    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The population of Quebec, Canada (7.3 million) contains ~6 million French Canadians; they are the descendants of ~8500 permanent French settlers who colonized Nouvelle France between 1608 and 1759. Their well-documented settlements, internal migrations, and natural increase over four centuries in relative isolation (geographic, linguistic, etc.) contain important evidence of social transmission of demographic behavior that contributed to effective family size and population structure. This history is reflected in at least 22 Mendelian diseases, occurring at unusually high prevalence in its subpopulations. Immigration of non-French persons during the past 250 years has given the Quebec population further inhomogeneity, which is apparent in allelic diversity at various loci. The histories of Quebec's subpopulations are, to a great extent, the histories of their alleles. Rare pathogenic alleles with high penetrance and associated haplotypes at 10 loci (CFTR, FAH, HBB, HEXA, LDLR, LPL, PAH, PABP2, PDDR, and SACS) are expressed in probands with cystic fibrosis, tyrosinemia, beta-thalassemia, Tay-Sachs, familial hypercholesterolemia, hyperchylomicronemia, PKU, oculopharyngeal muscular dystrophy, pseudo vitamin D deficiency rickets, and spastic ataxia of Charlevoix-Saguenay, respectively) reveal the interpopulation and intrapopulation genetic diversity of Quebec. Inbreeding does not explain the clustering and prevalence of these genetic diseases; genealogical reconstructions buttressed by molecular evidence point to founder effects and genetic drift in multiple instances. Genealogical estimates of historical meioses and analysis of linkage disequilibrium show that sectors of this young population are suitable for linkage disequilibrium mapping of rare alleles. How the population benefits from what is being learned about its structure and how its uniqueness could facilitate construction of a genomic map of linkage disequilibrium are discussed.
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    Topics: Biology
    Notes: The chapter describes some personal reminiscences of various stages in the growth of knowledge of the mouse genome in the past 50 years. Initially mapping was done by crossing new mutants with linkage testing stocks, a slow and laborious method. In the 1950s major mutagenesis experiments led to spin-offs in terms of new mutants, new knowledge of phenomena including sex determination and X-chromosome inactivation, and further understanding of the t-complex. The 1970s saw the development of recombinant inbred (RI) strains and the use of biochemical variants for mapping. In addition the linkage groups were assigned to chromosomes. Techniques of embryo surgery were developed, leading to work with embryonic stem (ES) cells and hence to the identification of gene functioning by knockouts and transgenesis. Another major advance in the 1970s and 1980s was the beginning of comparative mapping, which is now so important. With the advent of DNA technology, progress in mapping increased considerably. Progress became even faster with the use of interspecific backcrosses and with the development of microsatellite markers. The completion of the mouse DNA sequence is now imminent, opening fascinating prospects for the analysis of gene function.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Developmental pathways first elucidated by genetic studies in the fruit fly Drosophila melanogaster are conserved in vertebrates. The hedgehog pathway, first discovered because of its involvement in early Drosophila development, plays a key role in human embryogenesis. Dissruption of this pathway has been associated with congenital anomalies of the central nervous system, axial skeleton, limbs, and occasionally other organs. Many developmental genes continue to play an important role in regulation of cell growth and differentiation after embryogenesis, and mutations that lead to activation of the hedgehog pathway result in skin cancer and other malignancies in children and adults.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Genetic screens in Drosophila melanogaster, Caenorhabditis elegans, and Danio rerio clarified the logic of metazoan development by revealing critical unitary steps and pathways to embryogenesis. Can genetic screens similarly organize medicine? We here examine human diseases that resemble mutations in Danio rerio, the zebrafish, the one vertebrate species for which large-scale genetic screens have been performed and extensively analyzed. Zebrafish mutations faithfully phenocopy many human disorders. Each mutation, once cloned, provides candidate genes and pathways for evaluation in the human. The collection of mutations in their entirety potentially provides a medical taxonomy, one based in developmental biology and genetics.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Gene finding in genetically complex diseases has been difficult as a result of many factors that have diagnostic and methodologic considerations. For bipolar disorder and schizophrenia, numerous family, twin, and adoption studies have identified a strong genetic component to these behavioral psychiatric disorders. Despite difficulties that include diagnostic differences between sample populations and the lack of statistical significance in many individual studies, several promising patterns have emerged, suggesting that true susceptibility loci for schizophrenia and bipolar disorder may have been identified. In this review, the genetic epidemiology of these disorders is covered as well as linkage findings on chromosomes 4, 12, 13, 18, 21, and 22 in bipolar disorder and on chromosomes 1, 6, 8, 10, 13, 15, and 22 in schizophrenia. The sequencing of the human genome and identification of numerous single nucleotide polymorphisms (SNP) should substantially enhance the ability of investigators to identify disease-causing genes in these areas of the genome.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Fifty years after the publication of DNA structure, the whole human genome sequence will be officially finished. This achievement marks the beginning of the task to catalogue every human gene and identify each of their function expression patterns. Currently, researchers estimate that there are about 30,000 human genes and approximately 70% of these can be automatically predicted using a combination of ab initio and similarity-based programs. However, to experimentally investigate every gene's function, the research community requires a high-quality annotation of alternative splicing, pseudogenes, and promoter regions that can only be provided by manual intervention. Manual curation of the human genome will be a long-term project as experimental data are continually produced to confirm or refine the predictions, and new features such as noncoding RNAs and enhancers have not been fully identified. Such a highly curated human gene-set made publicly available will be a great asset for the experimental community and for future comparative genome projects.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Geneticists are interested in finding genes associated with disease. Because of widespread health disparities, race is a variable that is often said to be relevant in this context. The idea is that members of a preconceived "race" share common ancestry that may include genetic risk factors. Human variation has been shaped by the long-term processes of population history, and population samples that reflect that history carry statistical information about shared genetic variation or "ancestry." But race is an elusive concept and a term difficult even to define rigorously. Unfortunately, these problems are neither new nor related to recent genetic knowledge. Race is also one of the most politically charged subjects in American life because its associated sociocultural component has notoriously led to categorical treatment that has been misleading and politically misused. There are ways in which the concept of race (whether or not the term is used) can be a legitimate tool in the search for disease-associated genes. But in that context race reflects deeply confounded cultural as well as biological factors, and a careful distinction must be made between race as a statistical risk factor and causal genetic variables.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Genomic rearrangements play a major role in the pathogenesis of human genetic diseases. Nonallelic homologous recombination (NAHR) between low-copy repeats (LCRs) that flank unique genomic segments results in changes of genome organization and can cause a loss or gain of genomic segments. These LCRs appear to have arisen recently during primate speciation via paralogous segmental duplication, thus making the human species particularly susceptible to genomic rearrangements. Genomic disorders are defined as a group of diseases that result from genomic rearrangements, mostly mediated by NAHR. Molecular investigations of genomic disorders have revealed genome architectural features associated with susceptibility to rearrangements and the recombination mechanisms responsible for such rearrangements. The human genome sequence project reveals that LCRs may account for 5% of the genome, suggesting that many novel genomic disorders might still remain to be recognized.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract The polymorphisms within the human genome include several functional variants that cause debilitating inherited diseases. An elevated frequency of some of these deleterious mutations can be explained by a beneficial effect that confers a selective advantage owing to disease resistance in carriers of such mutations during an infectious disease outbreak. We here review plausible examples of balanced functional polymorphisms and their roles in the defense against pathogens. The genome organization of the chemokine receptor and HLA gene clusters and their influence on the HIV/AIDS epidemic provides compelling evidence for the interaction of infectious and genetic diseases in recent human history.
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  • 68
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Abstract Dynamical modeling of biological systems is becoming increasingly widespread as people attempt to grasp biological phenomena in their full complexity and make sense of an accelerating stream of experimental data. We review a number of recent modeling studies that focus on systems specifically involving gene expression and regulation. These systems include bacterial metabolic operons and phase-variable piliation, bacteriophages T7 and lamba, and interacting networks of eukaryotic developmental genes. A wide range of conceptual and mathematical representations of genetic components and phenomena appears in these works. We discuss these representations in depth and give an overview of the tools currently available for creating and exploring dynamical models. We argue that for modeling to realize its full potential as a mainstream biological research technique the tools must become more general and flexible, and formal, standardized representations of biological knowledge and data must be developed.
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    Topics: Biology
    Notes: Abstract Our goal with this article is to inform the debate over gene patenting, by providing an understanding of (a) the scope of patent claims that are actually being issued on genetic inventions in the United States, (b) the issues that impact their enforcement, and (c) the role that patents and patent licensing play in the commercialization of genetic technologies and products. We conclude by discussing whether the current legal regime effectively balances the beneficial role of patents in the development of new genetic technologies and products against negative impacts on genetic research or clinical genetic testing, or whether the current laws should be amended.
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    Source: Annual Reviews Electronic Back Volume Collection 1932-2001ff
    Topics: Biology
    Notes: Many internal organs in the vertebrate body are asymmetrically oriented along the left-right (L-R) body axis. Organ asymmetry and some components of the molecular signaling pathways that direct L-R development are highly conserved among vertebrate species. Although individuals with full reversal of organ L-R asymmetry (situs inversus totalis) are healthy, significant morbidity and mortality is associated with perturbations in laterality that result in discordant orientation of organ systems and complex congenital heart defects. In humans and other vertebrates, genetic alterations of L-R signaling pathways can result in a wide spectrum of laterality defects. In this review we categorize laterality defects in humans, mice, and zebrafish into specific classes based on altered patterns of asymmetric gene expression, organ situs defects, and midline phenotypes. We suggest that this classification system provides a conceptual framework to help consolidate the disparate laterality phenotypes reported in humans and vertebrate model organisms, thereby refining our understanding of the genetics of L-R development. This approach helps suggest candidate genes and genetic pathways that might be perturbed in human laterality disorders and improves diagnostic criteria.
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    Topics: Biology
    Notes: Human narcolepsy is a genetically complex disorder. Family studies indicate a 20-40 times increased risk of narcolepsy in first-degree relatives and twin studies suggest that nongenetic factors also play a role. The tight association between narcolepsy-cataplexy and the HLA allele DQB1*0602 suggests that narcolepsy has an autoimmune etiology. In recent years, extensive genetic studies in animals, using positional cloning in dogs and gene knockouts in mice, have identified abnormalities in hypothalamic hypocretin (orexin) neurotransmission as key to narcolepsy pathophysiology. Though most patients with narcolepsy-cataplexy are hypocretin deficient, mutations or polymorphisms in hypocretin-related genes are extremely rare. It is anticipated that susceptibility genes that are independent of HLA and impinge on the hypocretin neurotransmitter system are isolated in human narcolepsy.
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    Topics: Biology
    Notes: The progress in understanding the genetics of nonsyndromic epilepsy is the direct result of dramatic advances made by the Human Genome Project. The development of thousands of precisely mapped genetic markers and the nearly complete sequencing of the entire human genome in 2001 allowed genetic researchers in epilepsy to identify many loci and genes as causal in inherited idiopathic epilepsy. This substantial increase in information has required the development of accurate and online bioinformatic databases. Only the Internet can enable such large amounts of precise DNA sequence information to be transferred to researchers. Along with the construction of these databases has been the development of efficient search algorithms for specific DNA sequences and genetic information. This article summarizes the effect that this burst of new genomic information has had on research aimed at discovering the underlying genetic factors for nonsyndromic epilepsy. Many of the web sites important to epilepsy gene discovery are listed and discussed in this article, including sites with extensive information on genetic markers, genetic analysis, gene sequence, gene expression, gene mutations, and DNA sequence variation. Continued acquisition of information on naturally occurring DNA sequence variants will greatly help research directed towards understanding the genetic susceptibility of the common, nonsyndromic epilepsies and will lead to the promise of personalized medicine.
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    Topics: Biology
    Notes: Fifty years after the publication of DNA structure, the whole human genome sequence will be officially finished. This achievement marks the beginning of the task to catalogue every human gene and identify each of their function expression patterns. Currently, researchers estimate that there are about 30,000 human genes and approximately 70% of these can be automatically predicted using a combination of ab initio and similarity-based programs. However, to experimentally investigate every gene's function, the research community requires a high-quality annotation of alternative splicing, pseudogenes, and promoter regions that can only be provided by manual intervention. Manual curation of the human genome will be a long-term project as experimental data are continually produced to confirm or refine the predictions, and new features such as noncoding RNAs and enhancers have not been fully identified. Such a highly curated human gene-set made publicly available will be a great asset for the experimental community and for future comparative genome projects.
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