What\u27s In A Label? The Effects of Substance Types and Labels on Treatment Considerations and Stigma

Visitors (N = 579) to a science center read selected scenarios and evaluated the most likely outcome for a hypothetical substance abuser. Respondents were randomly assigned to one of six scenario conditions: a person with one of three different substance abuse problems (alcohol, tobacco, or cocaine) was crossed with two labels reflecting high or low substance dependence. Results indicated that: (1) cigarettes were viewed as a less serious substance abuse problem than were alcohol or cocaine (a person who smoked cigarettes was rated as more likely to recover from his problem, self-change was regarded as more appropriate and less stigma was associated with smoking than with the other two drugs); (2) non-abstinent recoveries of all types were greeted with skepticism; and (3) recovery was rated as more likely to occur from treatment than from self-change

Alcohol Consumption and Incident Stroke Among Older Adults.

Objectives: This study examines the relationship between alcohol consumption and incident stroke among older adults and tests whether alcohol consumption contributes to observed race and sex differences in stroke. Method: Data are from a U.S. national cohort of black and white adults aged 45 and older, the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. Current and past drinking levels were reported at baseline (2003-2007). Participants who had never had a stroke were followed for adjudicated stroke events through September 2015 (n = 27,265). We calculated Cox proportional hazard models for stroke, adjusting for demographic, socioeconomic, behavioral, and health characteristics. Results: Participants, mean age 64.7 years, consumed on average 2.2 drinks/week and experienced 1,140 first-time stroke events over median 9.1 years follow-up. Nondrinkers had a 12% higher risk of stroke than current drinkers; the risk of stroke among nondrinkers largely reflected high risks among past drinkers; these differences were explained by socioeconomic characteristics. Among current drinkers, light drinkers had significantly lower stroke risks than moderate drinkers after accounting for demographic, socioeconomic, behavioral, and health characteristics. Implications of alcohol did not differ between blacks and whites but did differ by sex: Especially among women, nondrinkers, and specifically past drinkers, had higher risks; these differences were largely explained by health characteristics and behaviors. Alcohol did not explain race and sex differences in stroke incidence. Discussion: Among older adults, those who used to, but no longer, drink had higher risks of stroke, especially among women; current light drinkers had the lowest risk of stroke

Cataclysmic Variables in the First Year of the Zwicky Transient Facility

Using selection criteria based on amplitude, time, and color, we have identified 329 objects as known or candidate cataclysmic variables (CVs) during the first year of testing and operation of the Zwicky Transient Facility. Of these, 90 are previously confirmed CVs, 218 are strong candidates based on the shape and color of their light curves obtained during 3–562 days of observation, and the remaining 21 are possible CVs but with too few data points to be listed as good candidates. Almost half of the strong candidates are within 10 deg of the galactic plane, in contrast to most other large surveys that have avoided crowded fields. The available Gaia parallaxes are consistent with sampling the low mass transfer CVs, as predicted by population models. Our follow-up spectra have confirmed Balmer/helium emission lines in 27 objects, with four showing high-excitation He ii emission, including candidates for an AM CVn, a polar, and an intermediate polar. Our results demonstrate that a complete survey of the Galactic plane is needed to accomplish an accurate determination of the number of CVs existing in the Milky Way

Biochemical characterization of protease activity of Nsp3 from SARS-CoV-2 and its inhibition by nanobodies

Of the 16 non-structural proteins (Nsps) encoded by SARS CoV-2, Nsp3 is the largest and plays important roles in the viral life cycle. Being a large, multidomain, transmembrane protein, Nsp3 has been the most challenging Nsp to characterize. Encoded within Nsp3 is the papain-like protease domain (PLpro) that cleaves not only the viral polypeptide but also K48-linked polyubiquitin and the ubiquitin-like modifier, ISG15, from host cell proteins. We here compare the interactors of PLpro and Nsp3 and find a largely overlapping interactome. Intriguingly, we find that near full length Nsp3 is a more active protease compared to the minimal catalytic domain of PLpro. Using a MALDI-TOF based assay, we screen 1971 approved clinical compounds and identify five compounds that inhibit PLpro with IC50s in the low micromolar range but showed cross reactivity with other human deubiquitinases and had no significant antiviral activity in cellular SARS-CoV-2 infection assays. We therefore looked for alternative methods to block PLpro activity and engineered competitive nanobodies that bind to PLpro at the substrate binding site with nanomolar affinity thus inhibiting the enzyme. Our work highlights the importance of studying Nsp3 and provides tools and valuable insights to investigate Nsp3 biology during the viral infection cycle

Changes in Mouse Thymus and Spleen after Return from the STS-135 Mission in Space

Our previous results with flight (FLT) mice showed abnormalities in thymuses and spleens that have potential to compromise immune defense mechanisms. In this study, the organs were further evaluated in C57BL/6 mice after Space Shuttle Atlantis returned from a 13-day mission. Thymuses and spleens were harvested from FLT mice and ground controls housed in similar animal enclosure modules (AEM). Organ and body mass, DNA fragmentation and expression of genes related to T cells and cancer were determined. Although significance was not obtained for thymus mass, DNA fragmentation was greater in the FLT group (P<0.01). Spleen mass alone and relative to body mass was significantly decreased in FLT mice (P<0.05). In FLT thymuses, 6/84 T cell-related genes were affected versus the AEM control group (P<0.05; up: IL10, Il18bp, Il18r1, Spp1; down: Ccl7, IL6); 15/84 cancer-related genes had altered expression (P<0.05; up: Casp8, FGFR2, Figf, Hgf, IGF1, Itga4, Ncam1, Pdgfa, Pik3r1, Serpinb2, Sykb; down: Cdc25a, E2F1, Mmp9, Myc). In the spleen, 8/84 cancer-related genes were affected in FLT mice compared to AEM controls (P<0.05; up: Cdkn2a; down: Birc5, Casp8, Ctnnb1, Map2k1, Mdm2, NFkB1, Pdgfa). Pathway analysis (apoptosis signaling and checkpoint regulation) was used to map relationships among the cancer–related genes. The results showed that a relatively short mission in space had a significant impact on both organs. The findings also indicate that immune system aberrations due to stressors associated with space travel should be included when estimating risk for pathologies such as cancer and infection and in designing appropriate countermeasures. Although this was the historic last flight of NASA’s Space Shuttle Program, exploration of space will undoubtedly continue

Cataclysmic Variables in the First Year of the Zwicky Transient Facility

Using selection criteria based on amplitude, time, and color, we have identified 329 objects as known or candidate cataclysmic variables (CVs) during the first year of testing and operation of the Zwicky Transient Facility. Of these, 90 are previously confirmed CVs, 218 are strong candidates based on the shape and color of their light curves obtained during 3–562 days of observation, and the remaining 21 are possible CVs but with too few data points to be listed as good candidates. Almost half of the strong candidates are within 10 deg of the galactic plane, in contrast to most other large surveys that have avoided crowded fields. The available Gaia parallaxes are consistent with sampling the low mass transfer CVs, as predicted by population models. Our follow-up spectra have confirmed Balmer/helium emission lines in 27 objects, with four showing high-excitation He ii emission, including candidates for an AM CVn, a polar, and an intermediate polar. Our results demonstrate that a complete survey of the Galactic plane is needed to accomplish an accurate determination of the number of CVs existing in the Milky Way

Evidence for Late-stage Eruptive Mass Loss in the Progenitor to SN2018gep, a Broad-lined Ic Supernova: Pre-explosion Emission and a Rapidly Rising Luminous Transient

We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.4 ± 0.1 mag hr-1) and luminous (Mg,peak = -20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The high peak luminosity (Lbol ≳ 3 × 1044 erg s-1), the short rise time (trise = 3 days in g band), and the blue colors at peak (g-r ∼ -0.4) all resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (Teff ≳ 40,000 K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (Mg ∼ Mr ≈ mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E γ,iso \u3c 4.9 × 10 48 erg, a limit on X-ray emission LX \u3c 1040 erg s-1, and a limit on radio emission ν Lν ≲ 1037 erg s-1. Taken together, we find that the early (\u3c 10 days) data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3 × 1014 cm) that was ejected in eruptive pre-explosion mass-loss episodes. The late-time (\u3e 10 days) light curve requires an additional energy source, which could be the radioactive decay of Ni-56

The Death Throes of a Stripped Massive Star: An Eruptive Mass-Loss History Encoded in Pre-Explosion Emission, a Rapidly Rising Luminous Transient, and a Broad-Lined Ic Supernova SN2018gep

We present detailed observations of ZTF18abukavn (SN2018gep), discovered in high-cadence data from the Zwicky Transient Facility as a rapidly rising (1.3 mag/hr) and luminous (M_(g,peak) = −20 mag) transient. It is spectroscopically classified as a broad-lined stripped-envelope supernova (Ic-BL SN). The rapid rise to peak bolometric luminosity and blue colors at peak (t_(rise)∼0.5-3 days, L_(bol)≳3×10^(44) erg sec^(−1), g−r = −0.3) resemble the high-redshift Ic-BL iPTF16asu, as well as several other unclassified fast transients. The early discovery of SN2018gep (within an hour of shock breakout) enabled an intensive spectroscopic campaign, including the highest-temperature (T_(eff) ≳ 40,000K) spectra of a stripped-envelope SN. A retrospective search revealed luminous (M_g ∼ M_r ≈ −14mag) emission in the days to weeks before explosion, the first definitive detection of precursor emission for a Ic-BL. We find a limit on the isotropic gamma-ray energy release E_(γ,iso) < 4.9×10^(48) erg, a limit on X-ray emission L_X < 10^(40) erg sec^(−1), and a limit on radio emission νL_ν ≲ 10^(37) erg sec^(−1). Taken together, we find that the data are best explained by shock breakout in a massive shell of dense circumstellar material (0.02 M⊙) at large radii (3×10^(14)cm) that was ejected in eruptive pre-explosion mass-loss episodes

The Zwicky Transient Facility: Data Processing, Products, and Archive

The Zwicky Transient Facility (ZTF) is a new robotic time-domain survey currently in progress using the Palomar 48-inch Schmidt Telescope. ZTF uses a 47 square degree field with a 600 megapixel camera to scan the entire northern visible sky at rates of ~3760 square degrees/hour to median depths of g ~ 20.8 and r ~ 20.6 mag (AB, 5sigma in 30 sec). We describe the Science Data System that is housed at IPAC, Caltech. This comprises the data-processing pipelines, alert production system, data archive, and user interfaces for accessing and analyzing the products. The realtime pipeline employs a novel image-differencing algorithm, optimized for the detection of point source transient events. These events are vetted for reliability using a machine-learned classifier and combined with contextual information to generate data-rich alert packets. The packets become available for distribution typically within 13 minutes (95th percentile) of observation. Detected events are also linked to generate candidate moving-object tracks using a novel algorithm. Objects that move fast enough to streak in the individual exposures are also extracted and vetted. The reconstructed astrometric accuracy per science image with respect to Gaia is typically 45 to 85 milliarcsec. This is the RMS per axis on the sky for sources extracted with photometric S/N >= 10. The derived photometric precision (repeatability) at bright unsaturated fluxes varies between 8 and 25 millimag. Photometric calibration accuracy with respect to Pan-STARRS1 is generally better than 2%. The products support a broad range of scientific applications: fast and young supernovae, rare flux transients, variable stars, eclipsing binaries, variability from active galactic nuclei, counterparts to gravitational wave sources, a more complete census of Type Ia supernovae, and Solar System objects.Comment: 30 pages, 16 figures, Published in PASP Focus Issue on the Zwicky Transient Facility (doi: 10.1088/1538-3873/aae8ac