801 research outputs found

    Crossing Crawford’s conceptual divide: monumental linear earthworks in later prehistoric and early medieval Britain

    Get PDF
    In its early decades, Antiquity regularly featured the subject of linear earthworks that crisscross the British landscape. Subsequently, however, discussion has been largely relegated to period-specific and local journals. As a result, interpretations of these imposing but often poorly dated earthworks have been drawn in the contrasting research traditions of later prehistory and the early medieval period. Here, the authors propose a comparative dialogue as a means for reinterpreting these landscape features, and as a lens through which to explore social complexity. Combined with advances in archaeometrical dating, this new approach promises to reinvigorate the study of some of Britain’s largest archaeological monuments

    Improved gene delivery to human saphenous vein cells and tissue using a peptide-modified adenoviral vector

    Get PDF
    The establishment of efficient gene delivery to target human tissue is a major obstacle for transition of gene therapy from the pre-clinical phases to the clinic. The poor long-term patency rates for coronary artery bypass grafting (CABG) is a major clinical problem that lacks an effective and proven pharmacological intervention. Late vein graft failure occurs due to neointima formation and accelerated atherosclerosis. Since CABG allows a clinical window of opportunity to genetically modify vein ex vivo prior to grafting it represents an ideal opportunity to develop gene-based therapies. Adenoviral vectors have been frequently used for gene delivery to vein ex vivo and pre-clinical studies have shown effective blockade in neointima development by overexpression of candidate therapeutic genes. However, high titers of adenovirus are required to achieve sufficient gene delivery to provide therapeutic benefit. Improvement in the uptake of adenovirus into the vessel wall would therefore be of benefit. Here we determined the ability of an adenovirus serotype 5 vector genetically-engineered with the RGD-4C integrin targeting peptide inserted into the HI loop (Ad-RGD) to improve the transduction of human saphenous vein smooth muscle cells (HSVSMC), endothelial cells (HSVEC) and intact saphenous vein compared to a non-modified virus (Ad-CTL). We exposed each cell type to virus for 10, 30 or 60 mins and measured transgene at 24 h post infection. For both HSVSMC and HSVEC Ad-RGD mediated increased transduction, with the largest increases observed in HSVSMC. When the experiments were repeated with intact human saphenous vein (the ultimate clinical target for gene therapy), again Ad-RGD mediated higher levels of transduction, at all clinically relevant exposures times (10, 30 and 60 mins tissue:virus exposure). Our study demonstrates the ability of peptide-modified Ad vectors to improve transduction to human vein graft cells and tissue and has important implications for gene therapy for CABG

    A Chandra X-ray Study of Cygnus A - II. The Nucleus

    Full text link
    We report Chandra ACIS and quasi-simultaneous RXTE observations of the nearby, powerful radio galaxy Cygnus A, with the present paper focusing on the properties of the active nucleus. In the Chandra observation, the hard (> a few keV) X-ray emission is spatially unresolved with a size \approxlt 1 arcsec (1.5 kpc, H_0 = 50 km s^-1 Mpc^-1) and coincides with the radio and near infrared nuclei. In contrast, the soft (< 2 keV) emission exhibits a bi-polar nebulosity that aligns with the optical bi-polar continuum and emission-line structures and approximately with the radio jet. In particular, the soft X-ray emission corresponds very well with the [O III] \lambda 5007 and H\alpha + [N II] \lambda\lambda 6548, 6583 nebulosity imaged with HST. At the location of the nucleus there is only weak soft X-ray emission, an effect that may be intrinsic or result from a dust lane that crosses the nucleus perpendicular to the source axis. The spectra of the various X-ray components have been obtained by simultaneous fits to the 6 detectors. The compact nucleus is detected to 100 keV and is well described by a heavily absorbed power law spectrum with \Gamma_h = 1.52^{+0.12}_{-0.12} (similar to other narrow line radio galaxies) and equivalent hydrogen column N_H (nuc) = 2.0^{+0.1}_{-0.2} \times 10^{23} cm^-2. (Abstract truncated).Comment: To be published in the Astrophysical Journal, v564 January 1, 2002 issue; 34 pages, 11 figures (1 color

    The Murmur of the Sleeping Black Hole: Detection of Nuclear Ultraviolet Variability in LINER Galaxies

    Get PDF
    LINER nuclei, which are present in many nearby galactic bulges, may be the manifestation of low-rate or low-radiative-efficiency accretion onto supermassive central black holes. However, it has been unclear whether the compact UV nuclear sources present in many LINERs are clusters of massive stars, rather than being directly related to the accretion process. We have used HST to monitor the UV variability of a sample of 17 galaxies with LINER nuclei and compact nuclear UV sources. Fifteen of the 17 galaxies were observed more than once, with two to five epochs per galaxy, spanning up to a year. We detect significant variability in most of the sample, with peak-to-peak amplitudes from a few percent to 50%. In most cases, correlated variations are seen in two independent bands (F250W and F330W). Comparison to previous UV measurements indicates, for many objects, long-term variations by factors of a few over decade timescales. Variability is detected in LINERs with and without detected compact radio cores, in LINERs that have broad H-alpha wings detected in their optical spectra (``LINER 1's''), and in those that do not (``LINER 2s''). This variability demonstrates the existence of a non-stellar component in the UV continuum of all types, and sets a lower limit to the luminosity of this component. We note a trend in the UV color (F250W/F330W) with spectral type - LINER 1s tend to be bluer than LINER 2s. This trend may indicate a link between the shape of the nonstellar continuum and the presence or the visibility of a broad-line region. In one target, the post-starburst galaxy NGC 4736, we detect variability in a previously noted UV source that is offset by 2.5" (60 pc in projection) from the nucleus. This may be the nearest example of a binary active nucleus, and of the process leading to black hole merging.Comment: accepted to Ap

    Revealing the Dusty Warm Absorber in MCG--6-30-15 with the Chandra HETG

    Full text link
    We present detailed evidence for a warm absorber in the Seyfert 1 galaxy MCG--6-30-15 and dispute earlier claims for relativistic O line emission. The HETG spectra show numerous narrow, unresolved (FWHM < 200 km/s) absorption lines from a wide range of ionization states of N, O, Mg, Ne, Si, S, Ar, and Fe. The O VII edge and 1s^2--1snp resonance line series to n=9 are clearly detected at rest in the AGN frame. We attribute previous reports of an apparently highly redshifted O VII edge to the 1s^2--1snp (n > 5) O VII resonance lines, and a neutral Fe L absorption complex. The shape of the Fe L feature is nearly identical to that seen in the spectra of several X-ray binaries, and in laboratory data. The implied dust column density agrees with that obtained from reddening studies, and gives the first direct X-ray evidence for dust embedded in a warm absorber. The O VIII resonance lines and weak edge are also detected, and the spectral rollover below 2 keV is explained by the superposition of numerous absorption lines and edges. We identify, for the first time, a KLL resonance in the O VI photoabsorption cross section, giving a measure of the O VI column density. The O VII (f) emission detected at the systemic velocity implies a covering fraction of ~5% (depending on the observed vs. time-averaged ionizing flux). Our observations show that a dusty warm absorber model is not only adequate to explain all the spectral features > 0.48 keV (< 26 \AA) the data REQUIRE it. This contradicts the interpretation of Branduardi-Raymont et al. (2001) that this spectral region is dominated by highly relativistic line emission from the vicinity of the black hole.Comment: 4.5 pages, 1 color figure, accepted (April 2001) for publication in ApJL, not many changes from the initial submission - updated/added some measuements for the O VII resonance series, and added a discussion about FeO2 grain

    An XMM-Newton Study of Six Narrow-Line Seyfert 1 Galaxies at z = 0.35--0.92

    Full text link
    We report a detailed analysis of the XMM-Newton spectra of six Narrow-Line Seyfert 1 (NLS1) galaxies at redshift z = 0.35--0.92. Compared with the NLS1s at lower redshift in the previously most-studied sample, these NLS1s have larger black hole (BH) masses (logMBH>7.5\log\,M_\text{BH}>7.5) with similar or even lower Eddington ratios. Our extended XMM-Newton sample of NLS1s shows strong soft X-ray excess emission below 2 keV. The quantified soft excess strength does not show an obvious discrepancy from previous studies of the lower-redshift NLS1s. The systematic effect in the measurement of the Eddington ratio mainly lies in the bolometric correction factor. We also tentatively fit the spectra assuming two more physical models for the soft excess: warm Comptonization and relativistic reflection from the inner accretion disk. In the first scenario, we confirm the ubiquity of a warm and optically thick corona. The behavior of a single source can be better explained by relativistic reflection, although we cannot distinguish which model is a more favorable explanation for the soft excess based on the best-fit statistics.Comment: 13 pages, 10 figure

    Broad iron K-alpha emission lines as a diagnostic of black hole spin

    Full text link
    We address the ability of broad iron emission lines from black hole accretion disks to diagnose the spin of the black hole. Using a high-resolution 3-dimensional MHD simulation of a geometrically-thin accretion disk in a Pseudo-Newtonian potential, we show that both the midplane density and the vertical column density of the accretion flow drop dramatically over a narrow range of radii close to the innermost stable circular orbit (ISCO). We argue that this drop of density is accompanied by a sharp increase in the ionization parameter of the X-ray photosphere, and that the resulting imprint of the ISCO on the X-ray reflection spectrum can be used to constrain spin. Motivated by this simulation, we construct a simplified toy-model of the accretion flow within the ISCO of a Kerr black hole, and use this model to estimate the systematic error on inferred black hole spin that may result from slight bleeding of the iron line emission to the region inside of the ISCO. We find that these systematic errors can be significant for slowly spinning black holes but become appreciably smaller as one considers more rapidly rotating black holes.Comment: 23 pages, 5 figures. Accepted for publication in the Astrophysical Journa

    Lrg1 Regulates β (1, 3)-Glucan Masking in Candida albicans through the Cek1 MAP Kinase Pathway

    Get PDF
    Candida albicans is among the most prevalent opportunistic human fungal pathogens. The ability to mask the immunogenic polysaccharide β (1,3)-glucan from immune detection via a layer of mannosylated proteins is a key virulence factor of C. albicans. We previously reported that hyperactivation of the Cek1 mitogen-activated protein (MAP) kinase pathway promotes β (1,3)-glucan exposure. In this communication, we report a novel upstream regulator of Cek1 activation and characterize the impact of Cek1 activity on fungal virulence. Lrg1 encodes a GTPase-activating protein (GAP) that has been suggested to inhibit the GTPase Rho1. We found that disruption of LRG1 causes Cek1 hyperactivation and β (1,3)-glucan unmasking. However, when GTPase activation was measured for a panel of GTPases, the lrg1ΔΔ mutant exhibited increased activation of Cdc42 and Ras1 but not Rho1 or Rac1. Unmasking and Cek1 activation in the lrg1ΔΔ mutant can be blocked by inhibition of the Ste11 MAP kinase kinase kinase (MAPKKK), indicating that the lrg1ΔΔ mutant acts through the canonical Cek1 MAP kinase cascade. In order to determine how Cek1 hyperactivation specifically impacts virulence, a doxycycline-repressible hyperactive STE11ΔN467 allele was expressed in C. albicans. In the absence of doxycycline, this allele overexpressed STE11ΔN467, which induced production of proinflammatory tumor necrosis factor alpha (TNF-α) from murine macrophages. This in vitrophenotype correlates with decreased colonization and virulence in a mouse model of systemic infection. The mechanism by which Ste11ΔN467 causes unmasking was explored with RNA sequencing (RNA-Seq) analysis. Overexpression of Ste11ΔN467 caused upregulation of the Cph1 transcription factor and of a group of cell wall-modifying proteins which are predicted to impact cell wall architecture
    corecore