Delayed kinetics of poliovirus RNA synthesis in a human cell line with reduced levels of hnRNP C proteins.

The hnRNP C heterotetramer [(C1(3))C2] binds RNA polymerase II transcripts in the nucleus, along with other proteins of the core hnRNP complex, and plays an important role in mRNA biogenesis and transport. Infection of HeLa cells with poliovirus causes hnRNP C to re-localize from the nucleus, where it is normally retained during interphase, to the cytoplasm. We have proposed that in the cytoplasm, the protein isoforms of hnRNP C participate in the recognition of viral specific RNAs by the poliovirus replication proteins and/or in the assembly of membrane-bound RNA replication complexes. In SK-OV-3 cells, which express reduced levels of hnRNP C compared to HeLa cells or 293 cells, the kinetics of poliovirus replication are delayed. hnRNP C is also re-localized from the nucleus to the cytoplasm in SK-OV-3 cells infected with poliovirus. Increased expression of hnRNP C in SK-OV-3 cells by transient transfection increases the rate of virus production and overall yield over that seen in mock-transfected cells. We propose that hnRNP C interacts with poliovirus RNA and replication proteins to increase the efficiency of viral genomic RNA synthesis

An Extreme-AO Search for Giant Planets around a White Dwarf --VLT/SPHERE performance on a faint target GD 50

CONTEXT. Little is known about the planetary systems around single white dwarfs although there is strong evidence that they do exist. AIMS. We performed a pilot study with the extreme-AO system on the Spectro-Polarimetric High-contrast Exoplanet REsearch (SPHERE) on the Very Large Telescopes (VLT) to look for giant planets around a young white dwarf, GD 50. METHODS. We were awarded science verification time on the new ESO instrument SPHERE. Observations were made with the InfraRed Dual-band Imager and Spectrograph in classical imaging mode in H band. RESULTS. Despite the faintness of the target (14.2 mag in R band), the AO loop was closed and a strehl of 37\% was reached in H band. No objects were detected around GD 50. We achieved a 5-sigma contrast of 6.2, 8.0 and 8.25 mags at 0{\farcs}2, 0{\farcs}4 and 0{\farcs}6 and beyond, respectively. We exclude any substellar objects more massive than 4.0 M$_\textrm{J}$ at 6.2 AU, 2.9 M$_\textrm{J}$ at 12.4 AU and 2.8 M$_\textrm{J}$ at 18.6 AU and beyond. This rivals the previous upper limit set by Spitzer. We further show that SPHERE is the most promising instrument available to search for close-in substellar objects around nearby white dwarfs.Comment: A&A letters, accepte

Interpreting the extended emission around three nearby debris disc host stars

Cool debris discs are a relic of the planetesimal formation process around their host star, analogous to the solar system's Edgeworth-Kuiper belt. As such, they can be used as a proxy to probe the origin and formation of planetary systems like our own. The Herschel Open Time Key Programmes "DUst around NEarby Stars" (DUNES) and "Disc Emission via a Bias-free Reconnaissance in the Infrared/Submillimetre" (DEBRIS) observed many nearby, sun-like stars at far-infrared wavelengths seeking to detect and characterize the emission from their circumstellar dust. Excess emission attributable to the presence of dust was identified from around $\sim$ 20% of stars. Herschel's high angular resolution ($\sim$ 7" FWHM at 100 $\mu$m) provided the capacity for resolving debris belts around nearby stars with radial extents comparable to the solar system (50 to 100 au). As part of the DUNES and DEBRIS surveys, we obtained observations of three debris disc stars, HIP 22263 (HD 30495), HIP 62207 (HD 110897), and HIP 72848 (HD 131511), at far-infrared wavelengths with the Herschel PACS instrument. Combining these new images and photometry with ancilliary data from the literature, we undertook simultaneous multi-wavelength modelling of the discs' radial profiles and spectral energy distributions using three different methodologies: single annulus, modified black body, and a radiative transfer code. We present the first far-infrared spatially resolved images of these discs and new single-component debris disc models. We characterize the capacity of the models to reproduce the disc parameters based on marginally resolved emission through analysis of two sets of simulated systems (based on the HIP 22263 and HIP 62207 data) with the noise levels typical of the Herschel images. We find that the input parameter values are recovered well at noise levels attained in the observations presented here.Comment: 13 pages, 5 figures, 5 tables, accepted for publication in A&

Multi-wavelength modeling of the spatially resolved debris disk of HD 107146

(abridged) We aim to constrain the location, composition, and dynamical state of planetesimal populations and dust around the young, sun-like (G2V) star HD 107146}. We consider coronagraphic observations obtained with the Advanced Camera for Surveys (HST/ACS) onboard the HST in broad V and broad I filters, a resolved 1.3mm map obtained with the Combined Array for Research in Millimeter-Wave Astronomy (CARMA), Spitzer/IRS low resolution spectra, and the spectral energy distribution (SED) of the object at wavelengths ranging from 3.5micron to 3.1mm. We complement these data with new coronagraphic high resolution observations of the debris disk using the Near Infrared Camera and Multi-Object Spectrometer (HST/NICMOS) aboard the HST in the F110W filter. The SED and images of the disk in scattered light as well as in thermal reemission are combined in our modeling using a parameterized model for the disk density distribution and optical properties of the dust. A detailed analytical model of the debris disk around HD 107146 is presented that allows us to reproduce the almost entire set of spatially resolved and unresolved multi-wavelength observations. Considering the variety of complementary observational data, we are able to break the degeneracies produced by modeling SED data alone. We find the disk to be an extended ring with a peak surface density at 131AU. Furthermore, we find evidence for an additional, inner disk probably composed of small grains released at the inner edge of the outer disk and moving inwards due to Poynting-Robertson drag. A birth ring scenario (i.e., a more or less broad ring of planetesimals creating the dust disk trough collisions) is found to be the most likely explanation of the ringlike shape of the disk.Comment: 15 pages, 9 figures, accepted for publication in A&

J004457+4123 (Sharov 21): not a remarkable nova in M31 but a background quasar with a spectacular UV flare

We announce the discovery of a quasar behind the disk of M31, which was previously classified as a remarkable nova in our neighbour galaxy. The paper is primarily aimed at the outburst of J004457+4123 (Sharov 21), with the first part focussed on the optical spectroscopy and the improvement in the photometric database. Both the optical spectrum and the broad band spectral energy distribution of Sharov 21 are shown to be very similar to that of normal, radio-quiet type 1 quasars. We present photometric data covering more than a century and resulting in a long-term light curve that is densely sampled over the past five decades. The variability of the quasar is characterized by a ground state with typical fluctuation amplitudes of ~0.2 mag around B~20.5, superimposed by a singular flare of ~2 yr duration (observer frame) with the maximum at 1992.81 where the UV flux has increased by a factor of ~20. The total energy in the flare is at least three orders of magnitudes higher than the radiated energy of the most luminous supernovae, provided that it comes from an intrinsic process and the energy is radiated isotropically. The profile of the flare light curve appears to be in agreement with the standard predictions for a stellar tidal disruption event where a ~10 M_sun giant star was shredded in the tidal field of a ~2...5 10^8 M_sun black hole. The short fallback time derived from the light curve requires an ultra-close encounter where the pericentre of the stellar orbit is deep within the tidal disruption radius. Gravitational microlensing provides an alternative explanation, though the probability of such a high amplification event is very low.Comment: Accepted for publication in Astronomy and Astrophysics, 14 pages, 11 figure

Collisional modelling of the AU Microscopii debris disc

The spatially resolved AU Mic debris disc is among the most famous and best-studied debris discs. We aim at a comprehensive understanding of the dust production and the dynamics of the disc objects with in depth collisional modelling including stellar radiative and corpuscular forces. Our models are compared to a suite of observational data for thermal and scattered light emission, ranging from the ALMA radial surface brightness profile at 1.3mm to polarisation measurements in the visible. Most of the data can be reproduced with a planetesimal belt having an outer edge at around 40au and subsequent inward transport of dust by stellar winds. A low dynamical excitation of the planetesimals with eccentricities up to 0.03 is preferred. The radial width of the planetesimal belt cannot be constrained tightly. Belts that are 5au and 17au wide, as well as a broad 44au-wide belt are consistent with observations. All models show surface density profiles increasing with distance from the star as inferred from observations. The best model is achieved by assuming a stellar mass loss rate that exceeds the solar one by a factor of 50. While the SED and the shape of the ALMA profile are well reproduced, the models deviate from the scattered light data more strongly. The observations show a bluer disc colour and a lower degree of polarisation for projected distances <40au than predicted by the models. The problem may be mitigated by irregularly-shaped dust grains which have scattering properties different from the Mie spheres used. From tests with a handful of selected dust materials, we derive a preference for mixtures of silicate, carbon, and ice of moderate porosity. We address the origin of the unresolved central excess emission detected by ALMA and show that it cannot stem from an additional inner belt alone. Instead, it should derive, at least partly, from the chromosphere of the central star.Comment: Astronomy and Astrophysics (accepted for publication), 18 pages, 11 figure

Einfluss der Sakrumfraktur auf das funktionelle Langzeitergebnis von Beckenringverletzungen

Zusammenfassung: In der Akutphase umfasst die Behandlung der Beckenringverletzung mit Beteiligung des iliosakralen Komplexes die effiziente Blutungskontrolle und Stabilisierung des Beckenrings. Für das Langzeitresultat sind jedoch neurologische Ausfälle, Fehlverheilungen des hinteren Beckenrings mit tieflumbalen Schmerzen und urologische Komplikationen entscheidend. Zwischen 1991 und 2000 wurden in unserer Klinik 173Patienten mit Sakrumfrakturen behandelt. Diese wurden im Rahmen einer lateralen Kompressionsfraktur (AO-Klassifikation TypB2) oder einer "vertical-shear-" (Typ-C-)Verletzung mit einer Dislokation von 1cm wurden operativ (n=33, 19%) versorgt. 112Patienten wurden nach durchschnittlich 4,9Jahren nachkontrolliert. Von den 39Patienten mit neurologischen Ausfällen (35%) zeigten lediglich 4 eine vollständige neurologische Erholung. Chronische tieflumbale Schmerzen traten selten (n=8, 7%) und nur bei einer Typ-C-Verletzung auf. Die geringe Inzidenz an lumbalen Schmerzen rechtfertigt die konservative Therapie wenig dislozierter (<1cm) Sakrumfrakturen. Entscheidend für das Langzeitergebnis sind neurologische Defizite, die bei 30% aller Patienten persistiere

Annotation and function of switch-like genes in health and disease

Gene expression microarrays provide transcript-level measurements across entire genomes and are traditionally used for differential expression analysis between health and disease or classification of disease subtypes. The abundance of gene expression microarray data currently available to the scientific community makes it possible to assess gene transcript levels among diverse tissue types for an entire genome. Gene expression is controlled over a wide range at the transcript level through complex interplay between DNA and regulatory proteins, resulting in gene expression profiles that can be represented as normal, graded, and bimodal (switch-like) distributions. It is our assertion that these distributions of gene expression, notably the bimodal distribution, result from biologically relevant regulation events. We have performed genome-scale identification and annotation of genes with bimodal, switch-like expression at the transcript level in human and mouse, using large microarray datasets for healthy tissue, in order to study the cellular pathways and regulatory mechanisms involving this class of genes. Our method implemented a likelihood ratio test to identify bimodal genes by comparing the best-fit two-component normal mixture, estimated using the expectation maximization algorithm, against a single-component normal distribution for each gene. This procedure identified roughly 15% of genes in human and mouse as bimodal, with a substantial overlap between human genes and their orthologous mouse counterparts. A survey of biological pathways revealed that the set of bimodal genes plays a role in cell communication and signaling with the external environment. Our analysis of regulatory sequence regions for bimodal genes revealed characteristics including enrichment of TATA boxes and an increased number of alternative transcription start sites. In addition to regulatory sequence analysis, we explored aspects of epigenetic regulation for their activity among the set of bimodal genes. We performed meta-analysis of gene expression microarray, DNA methylation, and histone methylation datasets representing human stem cells and liver tissue to reveal that the mode of expression within switch-like genes is primarily associated with histone methylation status. These results provide insight to normal patterns of histone methylation in healthy, differentiated tissue types. Aberrant methylation is a known marker in the progression of cancer, so these switch-like genes may also provide a valuable reference in disease diagnosis and prognosis. The method presented for bimodal gene identification also allows for an alternate approach to differential gene expression analysis between tissues and disease subtypes.Ph.D., Biomedical Engineering -- Drexel University, 200

Annotation and function of switch-like genes in health and disease

Gene expression microarrays provide transcript-level measurements across entire genomes and are traditionally used for differential expression analysis between health and disease or classification of disease subtypes. The abundance of gene expression microarray data currently available to the scientific community makes it possible to assess gene transcript levels among diverse tissue types for an entire genome. Gene expression is controlled over a wide range at the transcript level through complex interplay between DNA and regulatory proteins, resulting in gene expression profiles that can be represented as normal, graded, and bimodal (switch-like) distributions. It is our assertion that these distributions of gene expression, notably the bimodal distribution, result from biologically relevant regulation events. We have performed genome-scale identification and annotation of genes with bimodal, switch-like expression at the transcript level in human and mouse, using large microarray datasets for healthy tissue, in order to study the cellular pathways and regulatory mechanisms involving this class of genes. Our method implemented a likelihood ratio test to identify bimodal genes by comparing the best-fit two-component normal mixture, estimated using the expectation maximization algorithm, against a single-component normal distribution for each gene. This procedure identified roughly 15% of genes in human and mouse as bimodal, with a substantial overlap between human genes and their orthologous mouse counterparts. A survey of biological pathways revealed that the set of bimodal genes plays a role in cell communication and signaling with the external environment. Our analysis of regulatory sequence regions for bimodal genes revealed characteristics including enrichment of TATA boxes and an increased number of alternative transcription start sites. In addition to regulatory sequence analysis, we explored aspects of epigenetic regulation for their activity among the set of bimodal genes. We performed meta-analysis of gene expression microarray, DNA methylation, and histone methylation datasets representing human stem cells and liver tissue to reveal that the mode of expression within switch-like genes is primarily associated with histone methylation status. These results provide insight to normal patterns of histone methylation in healthy, differentiated tissue types. Aberrant methylation is a known marker in the progression of cancer, so these switch-like genes may also provide a valuable reference in disease diagnosis and prognosis. The method presented for bimodal gene identification also allows for an alternate approach to differential gene expression analysis between tissues and disease subtypes.Ph.D., Biomedical Engineering -- Drexel University, 200

Simultaneous Water Vapor and Dry Air Optical Path Length Measurements and Compensation with the Large Binocular Telescope Interferometer

The Large Binocular Telescope Interferometer uses a near-infrared camera to measure the optical path length variations between the two AO-corrected apertures and provide high-angular resolution observations for all its science channels (1.5-13 $\mu$m). There is however a wavelength dependent component to the atmospheric turbulence, which can introduce optical path length errors when observing at a wavelength different from that of the fringe sensing camera. Water vapor in particular is highly dispersive and its effect must be taken into account for high-precision infrared interferometric observations as described previously for VLTI/MIDI or the Keck Interferometer Nuller. In this paper, we describe the new sensing approach that has been developed at the LBT to measure and monitor the optical path length fluctuations due to dry air and water vapor separately. After reviewing the current performance of the system for dry air seeing compensation, we present simultaneous H-, K-, and N-band observations that illustrate the feasibility of our feedforward approach to stabilize the path length fluctuations seen by the LBTI nuller.Comment: SPIE conference proceeding