204 research outputs found

    TGFβ upregulates PAR-1 expression and signalling responses in A549 lung adenocarcinoma cells

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    The major high-affinity thrombin receptor, proteinase activated receptor-1 (PAR-1) is expressed at low levels by the normal epithelium but is upregulated in many types of cancer, including lung cancer. The thrombin-PAR-1 signalling axis contributes to the activation of latent TGFβ in response to tissue injury via an avβ6 integrin-mediated mechanism. TGFβ is a pleiotropic cytokine that acts as a tumour suppressor in normal and dysplastic cells but switches into a tumour promoter in advanced tumours. In this study we demonstrate that TGFβ is a positive regulator of PAR-1 expression in A549 lung adenocarcinoma cells, which in turn increases the sensitivity of these cells to thrombin signalling. We further demonstrate that this effect is Smad3-, ERK1/2-and Sp1-dependent. We also show that TGFβ-mediated PAR-1 upregulation is accompanied by increased expression of integrin av and β6 subunits. Finally, TGFβ pre-stimulation promotes increased migratory potential of A549 to thrombin. These data have important implications for our understanding of the interplay between coagulation and TGFβ signalling responses in lung cancer

    Morphologies and Spectral Energy Distributions of Extremely Red Galaxies in the GOODS-South Field

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    Using U'- through Ks-band imaging data in the GOODS-South field, we construct a large, complete sample of 275 ``extremely red objects'' (EROs; K_s<22.0, R-K_s>3.35; AB), all with deep HST/ACS imaging in B_435, V_606, i_775, and z_850, and well-calibrated photometric redshifts. Quantitative concentration and asymmetry measurements fail to separate EROs into distinct morphological classes. We therefore visually classify the morphologies of all EROs into four broad types: ``Early'' (elliptical-like), ``Late'' (disk galaxies), ``Irregular'' and ``Other'' (chain galaxies and low surface brightness galaxies), and calculate their relative fractions and comoving space densities. For a broad range of limiting magnitudes and color thresholds, the relative number of early-type EROs is approximately constant at 33-44%, and the comoving space densities of Early- and Late-type EROs are comparable. Mean rest-frame spectral energy distributions (SEDs) at wavelengths between 0.1 and 1.2 um are constructed for all EROs. The SEDs are extremely similar in their range of shapes, independent of morphological type. The implication is that any differences between the broad-band SEDs of Early-type EROs and the other types are relatively subtle, and there is no robust way of photometrically distinguishing between different morphological types with usual optical/near-infrared photometry.Comment: Submitted to the ApJL. A version with full-resolution figures, all GOODS data and all GOODS collaboration papers may be found at http://www.stsci.edu/science/goods

    A trust approach for sharing research reagents

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    The core feature of trusts-holding property for the benefit of others-is well suited to constructing a research community that treats reagents as public goods

    The Lick AGN Monitoring Project: Photometric Light Curves and Optical Variability Characteristics

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    The Lick AGN Monitoring Project targeted 13 nearby Seyfert 1 galaxies with the intent of measuring the masses of their central black holes using reverberation mapping. The sample includes 12 galaxies selected to have black holes with masses roughly in the range 10^6-10^7 solar masses, as well as the well-studied AGN NGC 5548. In conjunction with a spectroscopic monitoring campaign, we obtained broad-band B and V images on most nights from 2008 February through 2008 May. The imaging observations were carried out by four telescopes: the 0.76-m Katzman Automatic Imaging Telescope (KAIT), the 2-m Multicolor Active Galactic Nuclei Monitoring (MAGNUM) telescope, the Palomar 60-in (1.5-m) telescope, and the 0.80-m Tenagra II telescope. Having well-sampled light curves over the course of a few months is useful for obtaining the broad-line reverberation lag and black hole mass, and also allows us to examine the characteristics of the continuum variability. In this paper, we discuss the observational methods and the photometric measurements, and present the AGN continuum light curves. We measure various variability characteristics of each of the light curves. We do not detect any evidence for a time lag between the B- and V-band variations, and we do not find significant color variations for the AGNs in our sample.Comment: 16 pages, 20 figures, 8 tables, accepted for publication in ApJ

    The Lick AGN Monitoring Project: Broad-Line Region Radii and Black Hole Masses from Reverberation Mapping of Hbeta

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    We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7 M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission. We present here the light curves for the objects in this sample and the subsequent Hbeta time lags for the nine objects where these measurements were possible. The Hbeta lag time is directly related to the size of the broad-line region, and by combining the lag time with the measured width of the Hbeta emission line in the variable part of the spectrum, we determine the virial mass of the central supermassive black hole in these nine AGNs. The absolute calibration of the black hole masses is based on the normalization derived by Onken et al. We also examine the time lag response as a function of velocity across the Hbeta line profile for six of the AGNs. The analysis of four leads to ambiguous results with relatively flat time lags as a function of velocity. However, SBS 1116+583A exhibits a symmetric time lag response around the line center reminiscent of simple models for circularly orbiting broad-line region (BLR) clouds, and Arp 151 shows an asymmetric profile that is most easily explained by a simple gravitational infall model. Further investigation will be necessary to fully understand the constraints placed on physical models of the BLR by the velocity-resolved response in these objects.Comment: 24 pages, 16 figures and 13 tables, submitted to Ap

    The Size Evolution of High Redshift Galaxies

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    Hubble Space Telescope images of high-redshift galaxies selected via color and photometric redshifts are used to examine the size and axial-ratio distribution of galaxies as a function of redshift at lookback times t > 8 Gyr. These parameters are measured at rest-frame UV wavelengths (1200-2000 Angstroms) on images with a rest-frame resolution of less than 0.8 kpc. Galaxy radii are found to scale with redshift approximately as the inverse of the Hubble parameter H(z). This is in accord with the theoretical expectation that the typical sizes of the luminous parts of galaxies should track the expected evolution in the virial radius of dark-matter halos. The mean ratio of semi-major to semi-minor axis for a bright well-resolved sample of galaxies at z ~ 4 is b/a = 0.65, suggesting that these Lyman break galaxies are not drawn from a spheroidal population. However the median concentration index of this sample is C = 3.5, which is closer to the typical concentration indices, C ~ 4, of nearby elliptical galaxies than to the values, C<2 for local disk galaxies of type Sb and later.Comment: 5 pages, including 3 figures; uses emulateapj style; accepted by ApJL for publication in a special issue of early GOODS result

    Meta-analysis of genome-wide association studies of asthma in ethnically diverse North American populations.

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    Asthma is a common disease with a complex risk architecture including both genetic and environmental factors. We performed a meta-analysis of North American genome-wide association studies of asthma in 5,416 individuals with asthma (cases) including individuals of European American, African American or African Caribbean, and Latino ancestry, with replication in an additional 12,649 individuals from the same ethnic groups. We identified five susceptibility loci. Four were at previously reported loci on 17q21, near IL1RL1, TSLP and IL33, but we report for the first time, to our knowledge, that these loci are associated with asthma risk in three ethnic groups. In addition, we identified a new asthma susceptibility locus at PYHIN1, with the association being specific to individuals of African descent (P = 3.9 Ă— 10(-9)). These results suggest that some asthma susceptibility loci are robust to differences in ancestry when sufficiently large samples sizes are investigated, and that ancestry-specific associations also contribute to the complex genetic architecture of asthma

    Framing REDD+ in the Brazilian national media: how discourses evolved amid global negotiation uncertainties

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    Reducing emissions from deforestation and degradation (REDD+) in tropical countries is an important and contested element of the post-Kyoto climate regime. For policy options which generate controversy between diverse actor groups, such as REDD+, mass media plays an important role in defining and supporting policy possibilities. Analysis of the way in which national media frames issues of climate change and deforestation can offer insights into the nature of the contested domains of the REDD+ policy process. Here, we examine the Brazilian national media discourses surrounding REDD+ because it contributes to setting the tone of policy debates at the federal level. Specifically, we ask the following: (i) How was REDD+ portrayed in the Brazilian national print media and whose opinions and perceptions were represented? and (ii) How have media frames on REDD+ in the national print media changed over time? Our results contribute with new knowledge for understanding the observed progress of REDD+ in Brazil. We identify two main themes that dominate the focus in the national media coverage of REDD+, specifically “politics and policymaking” (representing half the coverage) and “economics and market” (with over a third). Results show that discussions around carbon markets were amongst the most contested and that optimism in relation to REDD+ effectiveness declined over time. The analysis suggests that positions adopted on the national REDD+ strategy were shaped by state and federal collision of interests. We demonstrate an evolution of national concerns from an initial focus on efficiency (e.g. finance and carbon markets) to a recentred focus on equity issues (e.g. implementation of safeguards). We conclude with some thoughts on the implications of these features for REDD+ interventions and implementation in Brazil

    First Results from the Lick AGN Monitoring Project: The Mass of the Black Hole in Arp 151

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    We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 13 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7 M_sun. We present here the first results from this project -- the mass of the central black hole in Arp 151. Strong variability throughout the campaign led to an exceptionally clean Hbeta lag measurement in this object of 4.25(+0.68/-0.66) days in the observed frame. Coupled with the width of the Hbeta emission line in the variable spectrum, we determine a black hole mass of (7.1 +/- 1.2)x10^6 M_sun, assuming the Onken et al. normalization for reverberation-based virial masses. We also find velocity-resolved lag information within the Hbeta emission line which clearly shows infalling gas in the Hbeta-emitting region. Further detailed analysis may lead to a full model of the geometry and kinematics of broad line region gas around the central black hole in Arp 151.Comment: 4 pages, 4 figures and 2 tables, accepted for publication in ApJ Letter
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