3,786 research outputs found

    Fetal-derived trophoblast use the apoptotic cytokine tumor necrosis factor-alpha-related apoptosis-inducing ligand to induce smooth muscle cell death.

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    Remodeling of the uterine spiral arteries during pregnancy transforms them from high to low resistance vessels that lack vasoconstrictive properties. This process is essential to meet the demand for increased blood flow imposed by the growing fetus. Loss of endothelial and smooth muscle cells (SMC) is evident in remodeled arteries but the mechanisms underlying this transformation remain unknown. This study investigated the hypothesis that fetal trophoblast invading from the placenta instigate remodeling by triggering cell death in vascular SMC. Specifically, a role for trophoblast-derived death inducing cytokine tumor necrosis factor-α–related apoptosis-inducing ligand (TRAIL) was investigated. Expression of the activating TRAIL receptors R1 and R2 was detected by flow cytometry on human aortic SMC and by immunohistochemistry on spiral artery SMC. Recombinant human TRAIL induced human aortic SMC apoptosis, which was inhibited by antibodies against TRAIL-R1 or -R2. Perfusion of denuded spiral artery segments with recombinant human TRAIL also induced SMC apoptosis. Trophoblasts isolated from first trimester placenta expressed membrane-associated TRAIL and induced apoptosis of human aortic SMC; apoptosis was significantly inhibited by a recombinant human TRAIL-R1:Fc construct. Trophoblast within the first trimester placental bed also expressed TRAIL. These data show that: 1) TRAIL causes SMC death; 2) trophoblast produce the apoptotic cytokine TRAIL; and 3) trophoblast induce SMC apoptosis via a TRAIL-dependent mechanism. We conclude that TRAIL produced by trophoblast causes apoptosis of SMC and thus may contribute to SMC loss during spiral artery remodeling in pregnancy

    The regional economic impact of more graduates in the labour market: a “micro-to-macro” analysis for Scotland

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    This paper explores the system-wide impact of graduates on the regional economy. Graduates enjoy a significant wage premium, often interpreted as reflecting their greater productivity relative to non-graduates. If this is so there is a clear and direct supply-side impact of HEI activities on regional economies. We use an HEI-disaggregated computable general equilibrium model of Scotland to estimate the impact of the growing proportion of graduates in the Scottish labour force that is implied by the current participation rate and demographic change, taking the graduate wage premium in Scotland as an indicator of productivity enhancement. While the detailed results vary with alternative assumptions about the extent to which wage premia reflect productivity, they do suggest that the long-term supply-side impacts of HEIs provide a significant boost to regional GDP. Furthermore, the results suggest that the supply-side impacts of HEIs are likely to be more important than the expenditure impacts that are the focus of most HEI impact studies

    Statistical Shape Analysis using Kernel PCA

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    ©2006 SPIE--The International Society for Optical Engineering. One print or electronic copy may be made for personal use only. Systematic reproduction and distribution, duplication of any material in this paper for a fee or for commercial purposes, or modification of the content of the paper are prohibited. The electronic version of this article is the complete one and can be found online at: http://dx.doi.org/10.1117/12.641417DOI:10.1117/12.641417Presented at Image Processing Algorithms and Systems, Neural Networks, and Machine Learning, 16-18 January 2006, San Jose, California, USA.Mercer kernels are used for a wide range of image and signal processing tasks like de-noising, clustering, discriminant analysis etc. These algorithms construct their solutions in terms of the expansions in a high-dimensional feature space F. However, many applications like kernel PCA (principal component analysis) can be used more effectively if a pre-image of the projection in the feature space is available. In this paper, we propose a novel method to reconstruct a unique approximate pre-image of a feature vector and apply it for statistical shape analysis. We provide some experimental results to demonstrate the advantages of kernel PCA over linear PCA for shape learning, which include, but are not limited to, ability to learn and distinguish multiple geometries of shapes and robustness to occlusions

    Which older people decline participation in a primary care trial of physical activity and why: insights from a mixed methods approach

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    This article is available through the Brunel Open Access Publishing Fund. Copyright 2014 Rogers et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background: Physical activity is of vital importance to older peoples’ health. Physical activity intervention studies with older people often have low recruitment, yet little is known about non-participants. Methods: Patients aged 60–74 years from three UK general practices were invited to participate in a nurse-supported pedometer-based walking intervention. Demographic characteristics of 298 participants and 690 non-participants were compared. Health status and physical activity of 298 participants and 183 non-participants who completed a survey were compared using age, sex adjusted odds ratios (OR) (95% confidence intervals). 15 non-participants were interviewed to explore perceived barriers to participation. Results: Recruitment was 30% (298/988). Participants were more likely than non-participants to be female (54% v 47%; p = 0.04) and to live in affluent postcodes (73% v 62% in top quintile; p < 0.001). Participants were more likely than non-participants who completed the survey to have an occupational pension OR 2.06 (1.35-3.13), a limiting longstanding illness OR 1.72 (1.05-2.79) and less likely to report being active OR 0.55 (0.33-0.93) or walking fast OR 0.56 (0.37-0.84). Interviewees supported general practice-based physical activity studies, particularly walking, but barriers to participation included: already sufficiently active, reluctance to walk alone or at night, physical symptoms, depression, time constraints, trial equipment and duration. Conclusion: Gender and deprivation differences suggest some selection bias. However, trial participants reported more health problems and lower activity than non-participants who completed the survey, suggesting appropriate trial selection in a general practice population. Non-participant interviewees indicated that shorter interventions, addressing physical symptoms and promoting confidence in pursuing physical activity, might increase trial recruitment and uptake of practice-based physical activity endeavours.The National Institute for Health Research (NIHR) under its Research for Patient Benefit Programme (Grant Reference Number PB-PG-0909-20055)

    Long-term spatiotemporal stability and dynamic changes in helminth infracommunities of bank voles (Myodes glareolus) in NE Poland

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    Parasites are considered to be an important selective force in host evolution but ecological studies of host-parasite systems are usually short-term providing only snap-shots of what may be dynamic systems. We have conducted four surveys of helminths of bank voles at three ecologically similar woodland sites in NE Poland, spaced over a period of 11 years, to assess the relative importance of temporal and spatial effects on helminth infracommunities. Some measures of infracom- munity structure maintained relative stability: the rank order of prevalence and abundance of Heligmosomum mixtum, Heligmosomoides glareoli and Mastophorus muris changed little between the four surveys. Other measures changed markedly: dynamic changes were evident in Syphacia petrusewiczi which declined to local extinction, while the capillariid Aonchotheca annulosa first appeared in 2002 and then increased in prevalence and abundance over the remaining three surveys. Some species are therefore dynamic and both introductions and extinctions can be expected in ecological time. At higher taxonomic levels and for derived measures, year and host-age effects and their interactions with site are import- ant. Our surveys emphasize that the site of capture is the major determinant of the species contributing to helminth community structure, providing some predictability in these systems

    Integrity of H1 helix in prion protein revealed by molecular dynamic simulations to be especially vulnerable to changes in the relative orientation of H1 and its S1 flank

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    In the template-assistance model, normal prion protein (PrPC), the pathogenic cause of prion diseases such as Creutzfeldt-Jakob (CJD) in human, Bovine Spongiform Encephalopathy (BSE) in cow, and scrapie in sheep, converts to infectious prion (PrPSc) through an autocatalytic process triggered by a transient interaction between PrPC and PrPSc. Conventional studies suggest the S1-H1-S2 region in PrPC to be the template of S1-S2 β\beta-sheet in PrPSc, and the conformational conversion of PrPC into PrPSc may involve an unfolding of H1 in PrPC and its refolding into the β\beta-sheet in PrPSc. Here we conduct a series of simulation experiments to test the idea of transient interaction of the template-assistance model. We find that the integrity of H1 in PrPC is vulnerable to a transient interaction that alters the native dihedral angles at residue Asn143^{143}, which connects the S1 flank to H1, but not to interactions that alter the internal structure of the S1 flank, nor to those that alter the relative orientation between H1 and the S2 flank.Comment: A major revision on statistical analysis method has been made. The paper now has 23 pages, 11 figures. This work was presented at 2006 APS March meeting session K29.0004 at Baltimore, MD, USA 3/13-17, 2006. This paper has been accepted for pubcliation in European Biophysical Journal on Feb 2, 200

    The Hubble Constant from Observations of the Brightest Red Giant Stars in a Virgo-Cluster Galaxy

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    The Virgo and Fornax clusters of galaxies play central roles in determining the Hubble constant H_0. A powerful and direct way of establishing distances for elliptical galaxies is to use the luminosities of the brightest red-giant stars (the TRGB luminosity, at M_I = -4.2). Here we report the direct observation of the TRGB stars in a dwarf elliptical galaxy in the Virgo cluster. We find its distance to be 15.7 +- 1.5 Megaparsecs, from which we estimate a Hubble constant of H_0 = 77 +- 8 km/s/Mpc. Under the assumption of a low-density Universe with the simplest cosmology, the age of the Universe is no more than 12-13 billion years.Comment: 12 pages, LaTeX, with 2 postscript figures; in press for Nature, July 199

    Sex-Specific Differences in Shoaling Affect Parasite Transmission in Guppies

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    Background: Individuals have to trade-off the costs and benefits of group membership during shoaling behaviour. Shoaling can increase the risk of parasite transmission, but this cost has rarely been quantified experimentally. Guppies (Poecilia reticulata) are a model system for behavioural studies, and they are commonly infected by gyrodactylid parasites, notorious fish pathogens that are directly transmitted between guppy hosts. Methodology/Principal Findings:Parasite transmission in single sex shoals of male and female guppies were observed using an experimental infection of Gyrodactylus turnbulli. Parasite transmission was affected by sex-specific differences in host behaviour, and significantly more parasites were transmitted when fish had more frequent and more prolonged contact with each other. Females shoaled significantly more than males and had a four times higher risk to contract an infection. Conclusions/Significance: Intersexual differences in host behaviours such as shoaling are driven by differences in natural and sexual selection experienced by both sexes. Here we show that the potential benefits of an increased shoaling tendency are traded off against increased risks of contracting an infectious parasite in a group-living species

    Swings between rotation and accretion power in a millisecond binary pulsar

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    It is thought that neutron stars in low-mass binary systems can accrete matter and angular momentum from the companion star and be spun-up to millisecond rotational periods. During the accretion stage, the system is called a low-mass X-ray binary, and bright X-ray emission is observed. When the rate of mass transfer decreases in the later evolutionary stages, these binaries host a radio millisecond pulsar whose emission is powered by the neutron star's rotating magnetic field. This evolutionary model is supported by the detection of millisecond X-ray pulsations from several accreting neutron stars and also by the evidence for a past accretion disc in a rotation-powered millisecond pulsar. It has been proposed that a rotation-powered pulsar may temporarily switch on during periods of low mass inflow in some such systems. Only indirect evidence for this transition has hitherto been observed. Here we report observations of accretion-powered, millisecond X-ray pulsations from a neutron star previously seen as a rotation-powered radio pulsar. Within a few days after a month-long X-ray outburst, radio pulses were again detected. This not only shows the evolutionary link between accretion and rotation-powered millisecond pulsars, but also that some systems can swing between the two states on very short timescales.Comment: 43 pages, 9 figures, 4 table. Published by Nature on 26 Sep 2013. Includes Supplementary information. Minor differences with published version may exis

    Study of psi(2S) decays to X J/psi

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    Using J/psi -> mu^+ mu^- decays from a sample of approximately 4 million psi(2S) events collected with the BESI detector, the branching fractions of psi(2S) -> eta J/psi, pi^0 pi^0 J/psi, and anything J/psi normalized to that of psi(2S) -> pi^+ pi^- J/psi are measured. The results are B(psi(2S) -> eta J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.098 \pm 0.005 \pm 0.010, B(psi(2S) -> pi^0 pi^0 J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 0.570 \pm 0.009 \pm 0.026, and B(psi(2S) -> anything J/psi)/B(psi(2S) -> pi^+ pi^- J/psi) = 1.867 \pm 0.026 \pm 0.055.Comment: 13 pages, 8 figure
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