The Three-Dimensional Structure of Cassiopeia A

We used the Spitzer Space Telescope's Infrared Spectrograph to map nearly the entire extent of Cassiopeia A between 5-40 micron. Using infrared and Chandra X-ray Doppler velocity measurements, along with the locations of optical ejecta beyond the forward shock, we constructed a 3-D model of the remnant. The structure of Cas A can be characterized into a spherical component, a tilted thick disk, and multiple ejecta jets/pistons and optical fast-moving knots all populating the thick disk plane. The Bright Ring in Cas A identifies the intersection between the thick plane/pistons and a roughly spherical reverse shock. The ejecta pistons indicate a radial velocity gradient in the explosion. Some ejecta pistons are bipolar with oppositely-directed flows about the expansion center while some ejecta pistons show no such symmetry. Some ejecta pistons appear to maintain the integrity of the nuclear burning layers while others appear to have punched through the outer layers. The ejecta pistons indicate a radial velocity gradient in the explosion. In 3-D, the Fe jet in the southeast occupies a "hole" in the Si-group emission and does not represent "overturning", as previously thought. Although interaction with the circumstellar medium affects the detailed appearance of the remnant and may affect the visibility of the southeast Fe jet, the bulk of the symmetries and asymmetries in Cas A are intrinsic to the explosion.Comment: Accepted to ApJ. 54 pages, 21 figures. For high resolution figures and associated mpeg movie and 3D PDF files, see http://homepages.spa.umn.edu/~tdelaney/pape

Locating the most energetic electrons in Cassiopeia A

We present deep ($>$2.4 Ms) observations of the Cassiopeia A supernova remnant with {\it NuSTAR}, which operates in the 3--79 keV bandpass and is the first instrument capable of spatially resolving the remnant above 15 keV. We find that the emission is not entirely dominated by the forward shock nor by a smooth "bright ring" at the reverse shock. Instead we find that the $>$15 keV emission is dominated by knots near the center of the remnant and dimmer filaments near the remnant's outer rim. These regions are fit with unbroken power-laws in the 15--50 keV bandpass, though the central knots have a steeper ($\Gamma \sim -3.35$) spectrum than the outer filaments ($\Gamma \sim -3.06$). We argue this difference implies that the central knots are located in the 3-D interior of the remnant rather than at the outer rim of the remnant and seen in the center due to projection effects. The morphology of $>$15 keV emission does not follow that of the radio emission nor that of the low energy ($<$12 keV) X-rays, leaving the origin of the $>$15 keV emission as an open mystery. Even at the forward shock front we find less steepening of the spectrum than expected from an exponentially cut off electron distribution with a single cutoff energy. Finally, we find that the GeV emission is not associated with the bright features in the {\it NuSTAR} band while the TeV emission may be, suggesting that both hadronic and leptonic emission mechanisms may be at work.Comment: 12 pages, 11 figures, accepted for publication in Ap

Perceived access and barriers to care among illicit drug users and hazardous drinkers: findings from the Seek, Test, Treat, and Retain data harmonization initiative (STTR).

BACKGROUND: Illicit drug use (DU) and hazardous drinking (HD) among marginalized populations may be associated with greater barriers to care. METHODS: We used baseline data on the participants of the Seek, Test, Treat, and Retain data harmonization initiative. DU includes use of any illicit drugs within the past 6 months. HD was defined as scores ≥8 for men and ≥ 7 for women on Alcohol Use Disorders Identification Test within the past 12 months. Social support scores were assigned by summing scores from individual questions related to social support. Two outcomes for multivariable regression models and mediation analysis were perceived access to care and perceived barriers to care scores, calculated from summated points from individual questions within each domain. All models were adjusted for age, gender, race/ethnicity, and social support and stratified by HIV status. RESULTS: Among 1403 illicit drug users and 4984 non-drug users, the mean age was 39.6 ± 12.2 years old, 71% were male, 57% African Americans, and 39% Hispanic/Latinos. Over 25% reported difficulties in covering medical costs and finding transportation to health care facilities and greater proportions of drug users and hazardous drinkers reported these issues than non-DU/non-HD. In multivariable models, DU and HD were both independently associated with having greater barriers to care (β: 0.49 (95% confidence interval: 0.19 to 0.79) p \u3c 0.01; 0.31 (0.18 to 0.45) \u3c 0.01) in HIV-negative participants. Neither DU nor HD was strongly associated with barriers to care for HIV-positive participants. Social support was associated with better perceived access to care and fewer barriers to care in the HIV-negative participants. CONCLUSION: The current study found that financial burdens of care, logistical difficulties in accessing care, and low social support were common challenges among individuals using illicit drugs and/or drinking hazardously. Addressing structural barriers and strengthening social support may be important strategies to improve health care among marginalized populations, regardless of HIV status

The distribution of radioactive 44Ti in Cassiopeia A

The distribution of elements produced in the innermost layers of a supernova explosion is a key diagnostic for studying the collapse of massive stars. Here we present the results of a 2.4 Ms NuSTAR observing campaign aimed at studying the supernova remnant Cassiopeia A (Cas A). We perform spatially resolved spectroscopic analyses of the 44Ti ejecta, which we use to determine the Doppler shift and thus the three-dimensional (3D) velocities of the 44Ti ejecta. We find an initial 44Ti mass of (1.54 ± 0.21) × 10−4 M⊙, which has a present-day average momentum direction of 340° ± 15° projected onto the plane of the sky (measured clockwise from celestial north) and is tilted by 58° ± 20° into the plane of the sky away from the observer, roughly opposite to the inferred direction of motion of the central compact object. We find some 44Ti ejecta that are clearly interior to the reverse shock and some that are clearly exterior to it. Where we observe 44Ti ejecta exterior to the reverse shock we also see shock-heated iron; however, there are regions where we see iron but do not observe 44Ti. This suggests that the local conditions of the supernova shock during explosive nucleosynthesis varied enough to suppress the production of 44Ti by at least a factor of two in some regions, even in regions that are assumed to be the result of processes like α-rich freezeout that should produce both iron and titanium

Cellular Growth Kinetics Distinguish a Cyclophilin Inhibitor from an HSP90 Inhibitor as a Selective Inhibitor of Hepatitis C Virus

During antiviral drug discovery, it is critical to distinguish molecules that selectively interrupt viral replication from those that reduce virus replication by adversely affecting host cell viability. In this report we investigate the selectivity of inhibitors of the host chaperone proteins cyclophilin A (CypA) and heat-shock protein 90 (HSP90) which have each been reported to inhibit replication of hepatitis C virus (HCV). By comparing the toxicity of the HSP90 inhibitor, 17-(Allylamino)-17-demethoxygeldanamycin (17-AAG) to two known cytostatic compounds, colchicine and gemcitabine, we provide evidence that 17-AAG exerts its antiviral effects indirectly through slowing cell growth. In contrast, a cyclophilin inhibitor, cyclosporin A (CsA), exhibited selective antiviral activity without slowing cell proliferation. Furthermore, we observed that 17-AAG had little antiviral effect in a non-dividing cell-culture model of HCV replication, while CsA reduced HCV titer by more than two orders of magnitude in the same model. The assays we describe here are useful for discriminating selective antivirals from compounds that indirectly affect virus replication by reducing host cell viability or slowing cell growth

Properties and distribution of paired candidate stony meteorites at Meridiani Planum, Mars

The Mars Exploration Rover Opportunity investigated four rocks, informally dubbed Barberton, Santa Catarina, Santorini, and Kasos, that are possible stony meteorites. Their chemical and mineralogical composition is similar to the howardite, eucrite, and diogenite group but with additional metal, similar to mesosiderite silicate clasts. Because of their virtually identical composition and because they appear to represent a relatively rare group of meteorites, they are probably paired. The four rocks were investigated serendipitously several kilometers apart, suggesting that Opportunity is driving across a larger population of similar rock fragments, maybe a meteorite strewn field. Small amounts of ferric Fe are a result of weathering. We did not observe evidence for fusion crusts. Four iron meteorites were found across the same area. Although mesosiderites are stony irons, a genetic link to these irons is unlikely. The stony meteorites probably fell later than the irons. The current atmosphere is sufficiently dense to land such meteorites at shallow entry angles, and it would disperse fragments over several kilometers upon atmospheric breakup. Alternatively, dispersion by spallation from an impacting meteoroid may have occurred. Santa Catarina and a large accumulation of similar rocks were found at the rim of Victoria crater. It is possible that they are associated with the impactor that created Victoria crater, but our limited knowledge about their distribution cannot exclude mere coincidence

The impact of donor and recipient common clinical and genetic variation on estimated glomerular filtration rate in a European renal transplant population

Genetic variation across the HLA is known to influence renal‐transplant outcome. However, the impact of genetic variation beyond the HLA is less clear. We tested the association of common genetic variation and clinical characteristics, from both the donor and recipient, with post‐transplant eGFR at different time‐points, out to 5‐years post‐transplantation. We conducted GWAS meta‐analyses across 10,844 donors and recipients from five European ancestry cohorts. We also analysed the impact of polygenic risk scores (PRS), calculated using genetic variants associated with non‐transplant eGFR, on post‐transplant eGFR. PRS calculated using the recipient genotype alone, as well as combined donor and recipient genotypes were significantly associated with eGFR at 1‐year post‐transplant. 32% of the variability in eGFR at 1‐year post‐transplant was explained by our model containing clinical covariates (including weights for death/graft‐failure), principal components and combined donor‐recipient PRS, with 0.3% contributed by the PRS. No individual genetic variant was significantly associated with eGFR post‐transplant in the GWAS. This is the first study to examine PRS, composed of variants that impact kidney function in the general population, in a post‐transplant context. Despite PRS being a significant predictor of eGFR post‐transplant, the effect size of common genetic factors is limited compared to clinical variables