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Showing papers by "University of Washington published in 1996"


Journal ArticleDOI
Claude Amsler1, Michael Doser2, Mario Antonelli, D. M. Asner3  +173 moreInstitutions (86)
TL;DR: This biennial Review summarizes much of particle physics, using data from previous editions.

12,798 citations


Journal ArticleDOI
TL;DR: Among women with low bone mass and existing vertebral fractures, alendronate is well tolerated and substantially reduces the frequency of morphometric and clinical vertebra fractures, as well as other clinical fractures.

3,730 citations


Journal ArticleDOI
TL;DR: After an average of four years of supplementation, the combination of beta carotene and vitamin A had no benefit and may have had an adverse effect on the incidence of lung cancer and on the risk of death from lung cancer, cardiovascular disease, and any cause in smokers and workers exposed to asbestos.
Abstract: Background Lung cancer and cardiovascular disease are major causes of death in the United States. It has been proposed that carotenoids and retinoids are agents that may prevent these disorders. Methods We conducted a multicenter, randomized, double-blind, placebo-controlled primary prevention trial — the Beta-Carotene and Retinol Efficacy Trial — involving a total of 18,314 smokers, former smokers, and workers exposed to asbestos. The effects of a combination of 30 mg of beta carotene per day and 25,000 IU of retinol (vitamin A) in the form of retinyl palmitate per day on the primary end point, the incidence of lung cancer, were compared with those of placebo. Results A total of 388 new cases of lung cancer were diagnosed during the 73,135 person-years of follow-up (mean length of follow-up, 4.0 years). The active-treatment group had a relative risk of lung cancer of 1.28 (95 percent confidence interval, 1.04 to 1.57; P = 0.02), as compared with the placebo group. There were no statistically significant ...

3,417 citations


Journal ArticleDOI
TL;DR: The events leading to the acquisition of HIV and the initial clinical and diagnostic evaluation of 46 patients with primary HIV infection are summarized.
Abstract: Background: The acute clinical events surrounding the acquisition of human immunodeficiency virus (HIV) have not been well characterized. Objective: To further define the clinical and epidemiologic...

3,331 citations


Book
15 Nov 1996
TL;DR: Spikes provides a self-contained review of relevant concepts in information theory and statistical decision theory about the representation of sensory signals in neural spike trains and a quantitative framework is used to pose precise questions about the structure of the neural code.
Abstract: Our perception of the world is driven by input from the sensory nerves. This input arrives encoded as sequences of identical spikes. Much of neural computation involves processing these spike trains. What does it mean to say that a certain set of spikes is the right answer to a computational problem? In what sense does a spike train convey information about the sensory world? Spikes begins by providing precise formulations of these and related questions about the representation of sensory signals in neural spike trains. The answers to these questions are then pursued in experiments on sensory neurons.The authors invite the reader to play the role of a hypothetical observer inside the brain who makes decisions based on the incoming spike trains. Rather than asking how a neuron responds to a given stimulus, the authors ask how the brain could make inferences about an unknown stimulus from a given neural response. The flavor of some problems faced by the organism is captured by analyzing the way in which the observer can make a running reconstruction of the sensory stimulus as it evolves in time. These ideas are illustrated by examples from experiments on several biological systems. Intended for neurobiologists with an interest in mathematical analysis of neural data as well as the growing number of physicists and mathematicians interested in information processing by "real" nervous systems, Spikes provides a self-contained review of relevant concepts in information theory and statistical decision theory. A quantitative framework is used to pose precise questions about the structure of the neural code. These questions in turn influence both the design and analysis of experiments on sensory neurons.

2,811 citations


Journal ArticleDOI
TL;DR: The findings indicate that the FAD–linked mutations may all cause Alzheimer's disease by increasing the extracellular concentration of Aβ42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.
Abstract: To determine whether the presenilin 1 (PS1), presenilin 2 (PS2) and amyloid beta-protein precursor (APP) mutations linked to familial Alzheimer's disease (FAD) increase the extracellular concentration of amyloid beta-protein (A beta) ending at A beta 42(43) in vivo, we performed a blinded comparison of plasma A beta levels in carriers of these mutations and controls. A beta 1-42(43) was elevated in plasma from subjects with FAD-linked PS1 (P < 0.0001), PS2N1411 (P = 0.009), APPK670N,M671L (P < 0.0001), and APPV7171 (one subject) mutations. A beta ending at A beta 42(43) was also significantly elevated in fibroblast media from subjects with PS1 (P < 0.0001) or PS2 (P = 0.03) mutations. These findings indicate that the FAD-linked mutations may all cause Alzhelmer's disease by increasing the extracellular concentration of A beta 42(43), thereby fostering cerebral deposition of this highly amyloidogenic peptide.

2,514 citations


Journal ArticleDOI
TL;DR: Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol.
Abstract: Objectives Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the...

2,211 citations


Journal ArticleDOI
TL;DR: In this paper, the authors present a model of the growth strategy of the firm in planned economies in transition such as Eastern Europe, the former Soviet republics, and China, focusing on the stylized state-owned enterprises.
Abstract: Highlighting an important facet of diversity among organizations operating in different institutional environments, this article presents a model of the growth strategy of the firm in planned economies in transition such as Eastern Europe, the former Soviet republics, and China. Focusing on the stylized state-owned enterprises, we explore the interaction between institutions and organizations in these countries. Given the institutional constraints, neither generic expansion nor acquisitions, two traditional strategies for growth found in the West, are viable for firms in these countries. Instead, firms settle on a network-based strategy of growth, building on personal trust and informal agreements among managers. The institutional environment that leads to this unique strategy of growth is examined, and boundary conditions, limitations, and implications of this model are discussed.

1,758 citations


Journal ArticleDOI
TL;DR: This list of scientists and lecturers from the United States and Canada who have contributed to the scientific literature over the past 25 years has been compiled.
Abstract: Mary E. Power is a professor in the Department of Integrative Biology, University of California, Berkeley, CA 94720. David Tilman is a professor in the Department of Ecology, Evolution, and Behavior, University of Minnesota, St. Paul, MN 55108. James A. Estes is a wildlife biologist in the National Biological Service, Institute of Marine Science, University of California, Santa Cruz, CA 95064. Bruce A. Menge is a professor in the Department of Zoology, Oregon State University, Corvallis, OR 97331. William J. Bond is a professor doctor in the Department of Botany, University of Cape Town, Rondebosch 7700 South Africa. L. Scott Mills is an assistant professor in the Wildlife Biology Program, School of Forestry, University of Montana, Missoula, MT 59812. Gretchen Daily is Bing Interdisciplinary Research Scientist, Department of Biological Science, Stanford University, Stanford, CA 94305. Juan Carlos Castilla is a full professor and marine biology head in Facultad de Ciencias Biologicas, Pontificia Universidad Catolica de Chile, Casilla 114-D, Santiago, Chile. Jane Lubchenco is a distinguished professor in the Department of Zoology, Oregon State University, Corvallis, OR 97331. Robert T. Paine is a professor in the Department of Zoology, NJ-15, University of Washington, Seattle, WA 98195. ? 1996 American Institute of Biological Sciences. A keystone species is

1,724 citations


Journal ArticleDOI
12 Apr 1996-Science
TL;DR: The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.
Abstract: Werner9s syndrome (WS) is an inherited disease with clinical symptoms resembling premature aging. Early susceptibility to a number of major age-related diseases is a key feature of this disorder. The gene responsible for WS (known as WRN ) was identified by positional cloning. The predicted protein is 1432 amino acids in length and shows significant similarity to DNA helicases. Four mutations in WS patients were identified. Two of the mutations are splice-junction mutations, with the predicted result being the exclusion of exons from the final messenger RNA. One of these mutations, which results in a frameshift and a predicted truncated protein, was found in the homozygous state in 60 percent of Japanese WS patients examined. The other two mutations are nonsense mutations. The identification of a mutated putative helicase as the gene product of the WS gene suggests that defective DNA metabolism is involved in the complex process of aging in WS patients.

1,673 citations


Journal ArticleDOI
01 Feb 1996-Nature
TL;DR: In this article, the authors proposed that multiple high-speed encounters between galaxies (galaxy harassment) drive the morphological evolution in clusters, and showed that these encounters are very different from mergers; they transform small disk galaxies into dwarf elliptical or dwarf spheroidal galaxies.
Abstract: NEARBY clusters of galaxies are filled with red elliptical 'E' and lenticular 'SO' galaxies1, while younger clusters (at redshifts of ≳ 0.4) contain substantial populations of blue spiral galaxies with morphological peculiarities2–7 (see Fig. 1). Thus, within the last 4–5 billion years, galaxies in clusters underwent strong evolution that completely changed their character. By contrast, galaxies that are not associated with clusters show far less morphological evolution8. Here we propose that multiple highspeed encounters between galaxies—'galaxy harassment'— drives the morphological evolution in clusters. Our simulations show that these encounters are very different from mergers; they transform small disk galaxies into dwarf elliptical or dwarf spheroidal galaxies. Harassment will leave detectable debris arcs and could provide fuel for quasars in sub-luminous host galaxies.

Journal ArticleDOI
31 May 1996-Cell
TL;DR: P27 deficiency may cause a cell-autonomous defect resulting in enhanced proliferation in response to mitogens, and in the spleen, the absence of p27 selectively enhanced proliferation of hematopoietic progenitor cells.

Journal ArticleDOI
TL;DR: The findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.
Abstract: The hypothesis that leptin (OB protein) acts in the hypothalamus to reduce food intake and body weight is based primarily on evidence from leptin-deficient, ob/ob mice. To investigate whether leptin exerts similar effects in normal animals, we administered leptin intracerebroventricularly (icv) to Long-Evans rats. Leptin administration (3.5 microg icv) at the onset of nocturnal feeding reduced food intake by 50% at 1 h and by 42% at 4 h, as compared with vehicle-treated controls (both P < 0.05). To investigate the basis for this effect, we used in situ hybridization (ISH) to determine whether leptin alters expression of hypothalamic neuropeptides involved in energy homeostasis. Two injections of leptin (3.5 microg icv) during a 40 h fast significantly decreased levels of mRNA for neuropeptide Y (NPY, which stimulates food intake) in the arcuate nucleus (-24%) and increased levels of mRNA for corticotrophin releasing hormone (CRH, an inhibitor of food intake) in the paraventricular nucleus (by 38%) (both P < 0.05 vs. vehicle-treated controls). To investigate the anatomic basis for these effects, we measured leptin receptor gene expression in rat brain by ISH using a probe complementary to mRNA for all leptin receptor splice variants. Leptin receptor mRNA was densely concentrated in the arcuate nucleus, with lower levels present in the ventromedial and dorsomedial hypothalamic nuclei and other brain areas involved in energy balance. These findings suggest that leptin action in rat hypothalamus involves altered expression of key neuropeptide genes, and implicate leptin in the hypothalamic response to fasting.

Journal ArticleDOI
TL;DR: Ecosystem management is management driven by explicit goals, executed by policies, protocols, and practices, and made adaptable by monitoring and research based on our best understanding of the ecological interactions and processes necessary to sustain ecosystem composition, structure, and function as discussed by the authors.
Abstract: Ecosystem management is management driven by explicit goals, executed by policies, protocols, and practices, and made adaptable by monitoring and research based on our best understanding of the ecological interactions and processes necessary to sustain ecosystem composition, structure, and function. In recent years, sustainability has become an explicitly stated, even legislatively mandated, goal of natural resource management agencies. In practice, however, management approaches have often focused on maximizing short-term yield and economic gain rather than long-term sustainability. Several obstacles contribute to this disparity, including: (1) inadequate information on the biological diversity of environments; (2) widespread ignorance of the function and dynamics of ecosystems; (3) the openness and interconnectedness of ecosystems on scales that transcend management boundaries; (4) a prevailing public perception that the immediate economic and social value of supposedly renewable resources outweighs the risk of future ecosystem damage or the benefits of alternative management approaches. The goal of ecosystem management is to overcome these obstacles. Ecosystem management includes the following elements: (1) Sustainability. Ecosystem management does not focus primarily on deliverables" but rather regards intergenerational sustainability as a precondition. (2) Goals. Ecosystem management establishes measurable goals that specify future processes and outcomes necessary for sustainability. (3) Sound ecological models and understanding. Ecosystem management relies on research performed at all levels of ecological organization. (4) Complexity and connectedness. Ecosystem management recognizes that biological diversity and structural complexity strengthen ecosystems against disturbance and supply the genetic resources necessary to adapt to long-term change. (5) The dynamic character of ecosystems. Recognizing that change and evolution are inherent in ecosystem sustainability, ecosystem management avoids attempts to freeze" ecosystems in a particular state or configuration. (6) Context and scale. Ecosystem processes operate over a wide range of spatial and temporal scales, and their behavior at any given location is greatly affected by surrounding systems. Thus, there is no single appropriate scale or time frame for management. (7) Humans as ecosystem components. Ecosystem management values the active role of humans in achieving sustainable management goals. (8) Adaptability and accountability. Ecosystem management acknowledges that current knowledge and paradigms of ecosystem function are provisional, incomplete, and subject to change. Management approaches must be viewed as hypotheses to be tested by research and monitoring programs. The following are fundamental scientific precepts for ecosystem management. (1) Spatial and temporal scale are critical. Ecosystem function includes inputs, outputs, cycling of materials and energy, and the interactions of organisms. Boundaries defined for the study or management of one process are often inappropriate for the study of others; thus, ecosystem management requires a broad view. (2) Ecosystem function depends on its structure, diversity, and integrity. Ecosystem management seeks to maintain biological diversity as a critical component in strengthening ecosystems against disturbance. Thus, management of biological diversity requires a broad perspective and recognition that the complexity and function of any particular location is influenced heavily by the surrounding system. (3) Ecosystems are dynamic in space and time. Ecosystem management is challenging in part because ecosystems are constantly changing. Over time scales of decades or centuries, many landscapes are altered by natural disturbances that lead to mosaics of successional patches of different ages. Such patch dynamics are critical to ecosystem structure and function. (4) Uncertainty, surprise, and limits to knowledge. Ecosystem management acknowledges that, given sufficient time and space, unlikely events are certain to occur. Adaptive management addresses this uncertainty by combining democratic principles, scientific analysis, education, and institutional learning to increase our understanding of ecosystem processes and the consequences of management interventions, and to improve the quality of data upon which decisions must be made. Ecosystem management requires application of ecological science to natural resource actions. Moving from concepts to practice is a daunting challenge and will require the following steps and actions. (1) Defining sustainable goals and objectives. Sustainable strategies for the provision of ecosystem goods and services cannot take as their starting points statements of need or want such as mandated timber supply, water demand, or arbitrarily set harvests of shrimp or fish. Rather, sustainability must be the primary objective, and levels of commodity and amenity provision must be adjusted to meet that goal. (2) Reconciling spatial scales. Implementation of ecosystem management would be greatly simplified if management jurisdictions were spatially congruent with the behavior of ecosystem processes. Given the variation in spatial domain among processes, one perfect fit for all processes is virtually impossible; rather, ecosystem management must seek consensus among the various stakeholders within each ecosystem. (3) Reconciling temporal scales. Whereas management agencies are often forced to make decisions on a fiscal-year basis, ecosystem management must deal with time scales that transcend human lifetimes. Ecosystem management requires long-term planning and commitment. (4) Making the system adaptable and accountable. Successful ecosystem management requires institutions that are adaptable to changes in ecosystem characteristics and in our knowledge base. Adaptive management by definition requires the scientist's ongoing interaction with managers and the public. Communication must flow in both directions, and scientists must be willing to prioritize their research with regard to critical management needs. Scientists have much to offer in the development of monitoring programs, particularly in creating sampling approaches, statistical analyses, and scientific models. As our knowledge base evolves, scientists must develop new mechanisms to communicate research and management results. More professionals with an understanding of scientific, management, and social issues, and the ability to communicate with scientists, managers, and the public are needed. Ecosystem management is not a rejection of an anthropocentric for a totally biocentric worldview. Rather it is management that acknowledges the importance of human needs while at the same time confronting the reality that the capacity of our world to meet those needs in perpetuity has limits and depends on the functioning of ecosystems.

Journal ArticleDOI
TL;DR: Surrogate end points are rarely, if ever, adequate substitutes for the definitive clinical outcome in phase 3 trials and proper justification for such replacement requires that the effect of the intervention on the surrogate end point predicts the effect on the clinical outcome.
Abstract: Phase 3 clinical trials, which evaluate the effect that new interventions have on the clinical outcomes of particular relevance to the patient (such as death, loss of vision, or other major symptom...

Journal ArticleDOI
01 Aug 1996-Stroke
TL;DR: White matter findings were significantly associated with age, silent stroke, hypertension, FEV1, and income, and may not be considered benign because they are associated with impaired cognitive and lower extremity function.
Abstract: Background and Purpose Our aim was to identify potential risk factors for and clinical manifestations of white matter findings on cranial MRI in elderly people. Methods Medicare eligibility lists were used to obtain a representative sample of 5888 community-dwelling people aged 65 years or older. Correlates of white matter findings were sought among 3301 participants who underwent MRI scanning and denied a history of stroke or transient ischemic attack. Participants underwent extensive standardized evaluations at baseline and on follow-up, including standard questionnaires, physical examination, multiple blood tests, electrocardiogram, pulmonary function tests, carotid sonography, and M-mode echocardiography. Neuroradiologists graded white matter findings from 0 (none) to 9 (maximal) without clinical information. Results Many potential risk factors were related to the white matter grade, but in the multivariate model the factors significantly (all P<.01) and independently associated with increased grade w...

Journal ArticleDOI
01 Feb 1996
TL;DR: Mechanical testing the modeling results for the McKibben artificial muscle pneumatic actuator, which contains an expanding tube surrounded by braided cords, and a linearized model of these properties for three different models is derived.
Abstract: This paper reports mechanical testing the modeling results for the McKibben artificial muscle pneumatic actuator. This device contains an expanding tube surrounded by braided cords. We report static and dynamic length-tension testing results and derive a linearized model of these properties for three different models. The results are briefly compared with human muscle properties to evaluate the suitability of McKibben actuators for human muscle emulation in biologically based robot arms.

01 Jan 1996
TL;DR: The platelet-derived growth factor has been shown in cell culture to be an extremely potent mitogen and will induce DNA synthesis and cell multiplication of a number of cells including smooth muscle cells, fibroblasts, and other mesenchymally derived cells as mentioned in this paper.
Abstract: The pathogenesis of atherosclerosis is hypothesized to occur as a response to various forms of injury to the lining arterial endothelial cells. The resulting endothelial alterations could potentially lead to interactions between platelets in the circulation and the underlying subendothelial connective tissue or with the altered endothelial cells themselves. Such interactions provide an opportunity for platelet degranulation and release of a platelet-derived growth factor. This factor has been shown in cell culture to be an extremely potent mitogen and will induce DNA synthesis and cell multiplication of a number of cells including smooth muscle cells, fibroblasts, and other mesenchymally derived cells. Chronic endothelial injury and repeated interactions between platelet-derived mitogens, plasma components, and the underlying arterial smooth muslce cells would promote the progression of the intimal proliferative lesions of atherosclerosis that lead to the clinical sequelae associated with this disease process.

Journal ArticleDOI
TL;DR: In this article, the authors provide an experimental test of the theory of change put forth by A. T. Beck, A. J.Rush, B. F. Shaw, and G. Emery (1979) to explain the efficacy of cognitive-behavioral therapy (CT) for depression.
Abstract: The purpose of this study was to provide an experimental test of the theory of change put forth by A. T. Beck, A. J. Rush, B. F. Shaw, and G. Emery (1979) to explain the efficacy of cognitive-behavioral therapy (CT) for depression. The comparison involved randomly assigning 150 outpatients with major depression to a treatment focused exclusively on the behavioral activation (BA) component of CT, a treatment that included both BA and the teaching of skills to modify automatic thoughts (AT), but excluding the components of CT focused on core schema, or the full CT treatment. Four experienced cognitive therapists conducted all treatments. Despite excellent adherence to treatment protocols by the therapists, a clear bias favoring CT, and the competent performance of CT, there was no evidence that the complete treatment produced better outcomes, at either the termination of acute treatment or the 6-month follow-up, than either component treatment. Furthermore, both BA and AT treatments were just as effective as CT at altering negative thinking as well as dysfunctional attributional styles. Finally, attributional style was highly predictive of both short- and long-term outcomes in the BA condition, but not in the CT condition.

Journal ArticleDOI
TL;DR: In this article, the authors define disturbance, natural or human-induced, as any event that measurably alters resources available to seagrasses so that a plant response is induced that results in degradation or loss.
Abstract: Many natural and human-induced events create disturbances in seagrasses throughout the world, but quantifying losses of habitat is only beginning. Over the last decade, 90000 ha of seagrass loss have been documented although the actual area lost is certainly greater. Seagrasses, an assemblage of marine flowering plant species, are valuable structural and functional components of coastal ecosystems and are currently experiencing worldwide decline. This group of plants is known to support a complex trophic food web and a detritus-based food chain, as well as to provide sediment and nutrient filtration, sediment stabilization, and breeding and nursery areas for finfish and shellfish.We define disturbance, natural or human-induced, as any event that measurably alters resources available to seagrasses so that a plant response is induced that results in degradation or loss. Applying this definition, we find a common thread in many seemingly unrelated seagrass investigations. We review reports of seagrass loss from both published and ‘grey’ literature and evaluate the types of disturbances that have caused seagrass decline and disappearance. Almost certainly more seagrass has been lost globally than has been documented or even observed, but the lack of comprehensive monitoring and seagrass. mapping makes an assessment of true loss of this resource impossible to determine.Natural disturbances that are most commonly responsible for seagrass loss include hurricanes, earthquakes, disease, and grazing by herbivores. Human activities most affecting seagrasses are those which alter water quality or clarity: nutrient and sediment loading from runoff and sewage disposal, dredging and filling, pollution, upland development, and certain fishing practices. Seagrasses depend on an adequate degree of water clarity to sustain productivity in their submerged environment. Although natural events have been responsible for both large-scale and local losses of seagrass habitat, our evaluation suggests that human population expansion is now the most serious cause of seagrass habitat loss, and specifically that increasing anthropogenic inputs to the coastal oceans are primarily responsible for the world-wide decline in seagrasses.

Journal ArticleDOI
16 Oct 1996-Langmuir
TL;DR: The presence of two sulfur species was detected in X-ray photoelectron spectroscopy (XPS) studies of thiol and disulfide molecules adsorbed onto gold surfaces as discussed by the authors.
Abstract: The presence of two sulfur species was detected in X-ray photoelectron spectroscopy (XPS) studies of thiol and disulfide molecules adsorbed onto gold surfaces. These species are assigned to bound thiolate (S2p3/2 binding energy of 162 eV) and unbound thiol/disulfide (S2p3/2 binding energy from 163.5 to 164 eV). These assignments are consistent with XPS data obtained from different thiols (C12, C16, C18, and C22 alkane thiols, a fluorinated thiol, and a cyclic polysiloxane thiol) and different adsorption conditions (solvent type, thiol concentration, temperature, and rinsing). In particular, the use of a poor solvent for thiol adsorption solutions (e.g., ethanol for long chain alkanethiols) and the lack of a rinsing step both resulted in unbound thiol molecules present at the surface of the bound thiolate monolayer. This has implications for recent studies asserting the presence of multiple binding sites for gold−thiolate species in organic monolayers.

Journal ArticleDOI
TL;DR: It is demonstrated thatosphorylation of beta-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo, which provides a basis for understanding the interaction between XgSk-3 and beta-catsin in the establishment of the dorsal-ventral axis in early Xenopus embryos.
Abstract: The serine/threonine kinase Xgsk-3 and the intracellular protein beta-catenin are necessary for the establishment of the dorsal-ventral axis in Xenopus. Although genetic evidence from Drosophila indicates that Xgsk-3 is upstream of beta-catenin, direct interactions between these proteins have not been demonstrated. We demonstrate that phosphorylation of beta-catenin in vivo requires an in vitro amino-terminal Xgsk-3 phosphorylation site, which is conserved in the Drosophila protein armadillo. beta-catenin mutants lacking this site are more active in inducing an ectopic axis in Xenopus embryos and are more stable than wild-type beta-catenin in the presence of Xgsk-3 activity, supporting the hypothesis that Xgsk-3 is a negative regulator of beta-catenin that acts through the amino-terminal site. Inhibition of endogenous Xgsk-3 function with a dominant-negative mutant leads to an increase in the steady-state levels of ectopic beta-catenin, indicating that Xgsk-3 functions to destabilize beta-catenin and thus decrease the amount of beta-catenin available for signaling. The levels of endogenous beta-catenin in the nucleus increases in the presence of the dominant-negative Xgsk-3 mutant, suggesting that a role of Xgsk-3 is to regulate the steady-state levels of beta-catenin within specific subcellular compartments. These studies provide a basis for understanding the interaction between Xgsk-3 and beta-catenin in the establishment of the dorsal-ventral axis in early Xenopus embryos.

01 Jan 1996
TL;DR: In this paper, the authors present a theory of antisocial behavior, the social development model, which organizes the results of research on risk and protec · tive factors for delinquency, crime, and substance abuse into hypQtheses regarding the development of prosocial and antisocial behaviour.
Abstract: This chapter presents a theory of antisocial behavior, the social development model, which organizes the results of research on risk and protec· tive factors for delinquency, crime, and substance abuse into hypQtheses regarding the development of antisocial and prosocial behavior. The social development model is grounded in tests of prior criminological theory. It hypothesizes similar general processes leading to prosocial and antisocial development, and specifies submodels for four specific periods during ch ildhood and adolescent development. Theoretical Considerations The social development model seeks to explain a broad range of distinct behaviors ranging from the use of illegal drugs to homicide. Crime, including violent and nonviolent offending and drug abuse, is viewed as a constellation of behaviors subject to the general principles incorporated in the model. .By considering evidence from research on the etiology .of both delinquency and drug abuse, it is possible to identify general constructs that predict both types of behavior and to use this knowledge in specifying predictive relationships in the development of antisocial behavior. ~ used here, the terms delinquency and drug use refer to behaviors. All behaviors are subject to influence from a variety of forces. The same principles, factors, or processes that influence one behavior should predict other behaviors. At the least, this suggests that a theory of antisocial behavior should be able to predict both drug use and criminal behavior, whether committed by children or adults. More ambitiously, it suggests a search for universal factors, mechanisms, or processes that predict all behavior. This implies a general theory. Gottfredson and Hirschi ( 1990), for example, have proposed "A General Theory of Crime," which attributes all criminal Preparation of this chapter was supported in part by grants from the National Insti· tute on Drug Abuse.

Journal ArticleDOI
TL;DR: The hypothesis that most early acting inbreeding depression is due to recessive lethals and can be purged through inbreeding, whereas much of the late‐acting inbreeding depressions are due to weakly deleterious mutations and is very difficult to purge, even under extreme inbreeding is supported.
Abstract: Estimates of inbreeding depression obtained from the literature were used to evaluate the association between inbreeding depression and the degree of self-fertilization in natural plant populations. Theoretical models predict that the magnitude of inbreeding depression will decrease with inbreeding as deleterious recessive alleles are expressed and purged through selection. If selection acts differentially among life history stages and deleterious effects are uncorrelated among stages, then the timing of inbreeding depression may also evolve with inbreeding. Estimates of cumulative inbreeding depression and stage-specific inbreeding depression (four stages: seed production of parent, germination, juvenile survival, and growth/reproduction) were compiled for 79 populations (using means of replicates, N = 62) comprising 54 species from 23 families of vascular plants. Where available, data on the mating system also were collected and used as a measure of inbreeding history. A significant negative correlation was found between cumulative inbreeding depression and the primary selfing rate for the combined sample of angiosperms (N = 35) and gymnosperms (N = 9); the correlation was significant for angiosperms but not gymnosperms examined separately. The average inbreeding depression in predominantly selfing species (8 = 0.23) was significantly less (43%) than that in predominantly outcrossing species (8 = 0.53). These results support the theoretical prediction that selfing reduces the magnitude of inbreeding depression. Most self-fertilizing species expressed the majority of their inbreeding de- pression late in the life cycle, at the stage of growth/reproduction (14 of 18 species), whereas outcrossing species expressed much of their inbreeding depression either early, at seed production (17 of 40 species), or late (19 species). For species with four life stages examined, selfing and outcrossing species differed in the magnitude of inbreeding depression at the stage of seed production (selfing 8 = 0.05, N = 11; outcrossing 8 = 0.32, N = 31), germination (selfing 8 = 0.02, outcrossing 8 = 0.12), and survival to reproduction (selfing 8 = 0.04, outcrossing 8 = 0.15), but not at growth and reproduction (selfing 8 = 0.21, outcrossing 8 = 0.27); inbreeding depression in selfers relative to outcrossers increased from early to late life stages. These results support the hypothesis that most early acting inbreeding depression is due to recessive lethals and can be purged through inbreeding, whereas much of the late-acting inbreeding depression is due to weakly deleterious mutations and is very difficult to purge, even under extreme inbreeding.

Journal ArticleDOI
TL;DR: The concept of meta-emotion philosophy was introduced in this paper, which refers to an organized set of feelings and thoughts about one's own emotions and one's children's emotions.
Abstract: This article introduces the concepts of parental meta-emotion, which refers to parents' emotions about their own and their children's emotions, and meta-emotion philosophy, which refers to an organized set of thoughts and metaphors, a philosophy, and an approach to one's own emotions and to one's children's emotions. In the context of a longitudinal study beginning when the children were 5 years old and ending when they were 8 years old, a theoretical model and path analytic models are presented that relate parental meta-emotion philosophy to parenting, to child regulatory physiology, to emotion regulation abilities in the child, and to child outcomes in middle childhood. The importance of parenting practices for children's long-term psychological adjustment has been a central tenet in developmental and family psychology. In this article, we introduce a new concept of parenting that we call parental meta-emotion philosophy, which refers to an organized set of feelings and thoughts about one's own emotions and one's children's emotions. We use the term meta-emotion broadly to encompass both feelings and thoughts about emotion, rather than in the more narrow sense of one's feelings about feelings (e.g., feeling guilty about being angry). The notion we have in mind parallels metacognition, which refers to the executive functions of cognition (Allen & Armour, 1993; Bvinelli, 1993; Flavell, 1979; Fodor, 1992; Olson & Astington, 1993). In an analogous manner, meta-emotion philosophy

Journal ArticleDOI
06 Dec 1996-Science
TL;DR: The results suggest that during Neogene time the underthrusting Indian crust has acted as a plunger, displacing the molten middle crust to the north while at the same time contributing to this layer by melting and ductile flow.
Abstract: INDEPTH geophysical and geological observations imply that a partially molten midcrustal layer exists beneath southern Tibet. This partially molten layer has been produced by crustal thickening and behaves as a fluid on the time scale of Himalayan deformation. It is confined on the south by the structurally imbricated Indian crust underlying the Tethyan and High Himalaya and is underlain, apparently, by a stiff Indian mantle lid. The results suggest that during Neogene time the underthrusting Indian crust has acted as a plunger, displacing the molten middle crust to the north while at the same time contributing to this layer by melting and ductile flow. Viewed broadly, the Neogene evolution of the Himalaya is essentially a record of the southward extrusion of the partially molten middle crust underlying southern Tibet.

Journal ArticleDOI
TL;DR: It is demonstrated that leptin stimulates the reproductive endocrine system in both sexes of ob/ob mice and suggested that leptin may serve as a permissive signal to the reproductive system of normal animals.
Abstract: Leptin, a newly-discovered hormonal product of the obese (ob) gene, is expressed by adipocytes and thought to play a role in the regulation of food intake and metabolism. We tested the hypothesis that leptin signals metabolic information to the reproductive system by examining its effects on the reproductive system of ob/ob mice, which have a congenital deficiency in leptin and are infertile. We treated pair-fed males and females with leptin (50 microg twice daily, ip) or vehicle (n=10/group) for 14 days, after which the animals were bled and killed. Leptin-treated females had significantly elevated serum levels of LH, increased ovarian and uterine weights, and stimulated aspects of ovarian and uterine histology compared to controls. Leptin-treated males had significantly elevated serum levels of FSH, increased testicular and seminal vesicle weights, greater seminal vesicle epithelial cell height, and elevated sperm counts compared to controls. These results demonstrate that leptin stimulates the reproductive endocrine system in both sexes of ob/ob mice and suggest that leptin may serve as a permissive signal to the reproductive system of normal animals.

Journal ArticleDOI
30 May 1996-Nature
TL;DR: It is reported here that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation, and mutants are more susceptible to seizures induced by a GABA (γ-aminobutyric acid) antagonist when treated with recombinant leptin.
Abstract: NEUROPEPTIDE Y (NPY), a 36-amino-acid transmitter distributed throughout the nervous system1,2, is thought to function as a central stimulator of feeding behaviour1–4. NPY has also been implicated in the modulation of mood5, cerebrocortical excitability6, hypothalamic–pituitary signalling7, cardiovascular physiology1,8 and sympathetic function9,10. However, the biological significance of NPY has been difficult to establish owing to a lack of pharmacological antagonists. We report here that mice deficient for NPY have normal food intake and body weight, and become hyperphagic following food deprivation. Mutant mice decrease their food intake and lose weight, initially to a greater extent than controls, when treated with recombinant leptin. Occasional, mild seizures occur in NPY-deficient mice and mutants are more susceptible to seizures induced by a GABA (γ-aminobutyric acid) antagonist. These results indicate that NPY is not essential for certain feeding responses or leptin actions but is an important modulator of excitability in the central nervous system.

Journal ArticleDOI
Joseph L. Blackshear1, Vickie S. Baker1, F. Rubino1, Robert E. Safford1  +152 moreInstitutions (21)
TL;DR: Low-intensity, fixed-dose warfarin plus aspirin in this regimen is insufficient for stroke prevention in patients with non-valvular AF at high-risk for thromboembolism; adjusted-doseWarfarin (target INR 2.0-3.0) importantly reduces stroke for high- risk patients.

Journal ArticleDOI
TL;DR: It is hypothesized that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance.
Abstract: The adipocyte hormone, leptin (OB protein), is proposed to be an "adiposity signal" that acts in the brain to lower food intake and adiposity. As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance. To investigate the mechanisms underlying brain leptin uptake and to determine whether reduced uptake may contribute to leptin resistance, we measured immunoreactive leptin levels in plasma and cerebrospinal fluid (CSF) of 53 human subjects. Leptin concentrations in CSF were strongly correlated to the plasma level in a nonlinear manner (r = 0.92; p = 0.0001). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; p = 0.001), demonstrating that plasma leptin enters human cerebrospinal fluid in proportion to body adiposity. However, the efficiency of this uptake (measured as the CSF:plasma leptin ratio) was lower among those in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference). We hypothesize that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance.