REFINED ORBITAL SOLUTION AND QUIESCENT VARIABILITY IN THE BLACK HOLE TRANSIENT GS 1354-64 (= BW Cir)

In Casares et al. we presented the first radial velocity curve of the companion star to BW Cir which demonstrates the presence of a black hole in this historical X-ray transient. But these data were affected by aliasing and two possible periods at 2.5445 days and 2.5635 days were equally possible. Here we present new spectroscopic data that enable us to break the 1-year aliasing and confirm 2.5445 days as the correct orbital period. We also present R-band photometry over 14 years, which reveals the presence of important flaring activity dominating the light curves.Spain. Ministerio de Ciencia y Tecnología (Spanish MCYT grant AYA2002-0036)Spain. Ministerio de Ciencia y Tecnología (programme Ramon y Cajal)Chandra X-ray Center (U.S.) (NASA Contract NAS8-03060

The Chemical Evolution Carousel of Spiral Galaxies : Azimuthal Variations of Oxygen Abundance in NGC1365

19 pages, 13 figures. Accepted to ApJThe spatial distribution of oxygen in the interstellar medium of galaxies is the key to understanding how efficiently metals that are synthesized in massive stars can be redistributed across a galaxy. We present here a case study in the nearby spiral galaxy NGC1365 using 3D optical data obtained in the TYPHOON Program. We find systematic azimuthal variations of the HII region oxygen abundance imprinted on a negative radial gradient. The 0.2 dex azimuthal variations occur over a wide radial range of 0.3 to 0.7 R25 and peak at the two spiral arms in NGC1365. We show that the azimuthal variations can be explained by two physical processes: gas undergoes localized, sub-kpc scale self-enrichment when orbiting in the inter-arm region, and experiences efficient, kpc scale mixing-induced dilution when spiral density waves pass through. We construct a simple chemical evolution model to quantitatively test this picture and find that our toy model can reproduce the observations. This result suggests that the observed abundance variations in NGC1365 are a snapshot of the dynamical local enrichment of oxygen modulated by spiral-driven, periodic mixing and dilution.Peer reviewedFinal Published versio

An Improved Dynamical Model for the Microquasar XTE J1550-564

We present an improved dynamical model of the X-ray binary and microquasar XTE J1550-564 based on new moderate-resolution optical spectroscopy and near-infrared photometry. By combining our new radial velocity measurements with previous measurements obtained 2001 May at the 8.2m VLT and with light curves, we find an orbital period of P=1.5420333 +/- 0.0000024 days and a radial velocity semiamplitude of K_2=363.14 +/- 5.97$ km/sec, which together imply an optical mass function of f(M)=7.65 +/- 0.38 solar masses. We find that the projected rotational velocity of the secondary star is 55 +/- 5 km/sec, which implies a very extreme mass ratio of Q=M/M_2=30. Using a model of a Roche lobe-filling star and an azimuthally symmetric accretion disk, we fit simultaneously optical light curves from 2001, near-infrared light curves from 2008 and all of the radial velocity measurements to derive system parameters. We find an inclination of 74.7 +/- 3.8 deg and component masses of M_2=0.30 +/- 0.07 solar masses and M=9.10 +/- 0.61 solar masses for the secondary star and black hole, respectively. The radius of the secondary star for the adopted model is 1.75 +/- 0.12 solar radii. Using this radius, the average K_S magnitude, and an extinction of A_K=0.507 +/- 0.050 mag, we find a distance of 4.38^{+0.58}_{-0.41} kpc, which is in good agreement with a recent distance estimate based on HI absorption lines (abstract shortened).Comment: 29 pages, 11 figures, to appear in ApJ, figures 1 and 2 are compresse

Healthcare workers hospitalized due to COVID-19 have no higher risk of death than general population. Data from the Spanish SEMI-COVID-19 Registry

Aim To determine whether healthcare workers (HCW) hospitalized in Spain due to COVID-19 have a worse prognosis than non-healthcare workers (NHCW). Methods Observational cohort study based on the SEMI-COVID-19 Registry, a nationwide registry that collects sociodemographic, clinical, laboratory, and treatment data on patients hospitalised with COVID-19 in Spain. Patients aged 20-65 years were selected. A multivariate logistic regression model was performed to identify factors associated with mortality. Results As of 22 May 2020, 4393 patients were included, of whom 419 (9.5%) were HCW. Median (interquartile range) age of HCW was 52 (15) years and 62.4% were women. Prevalence of comorbidities and severe radiological findings upon admission were less frequent in HCW. There were no difference in need of respiratory support and admission to intensive care unit, but occurrence of sepsis and in-hospital mortality was lower in HCW (1.7% vs. 3.9%; p = 0.024 and 0.7% vs. 4.8%; p<0.001 respectively). Age, male sex and comorbidity, were independently associated with higher in-hospital mortality and healthcare working with lower mortality (OR 0.211, 95%CI 0.067-0.667, p = 0.008). 30-days survival was higher in HCW (0.968 vs. 0.851 p<0.001). Conclusions Hospitalized COVID-19 HCW had fewer comorbidities and a better prognosis than NHCW. Our results suggest that professional exposure to COVID-19 in HCW does not carry more clinical severity nor mortality

Comparative Analysis of Human Nucleoside Kinase-Based Reporter Systems for PET Imaging

PurposeRadionuclide-based reporter gene imaging has the sensitivity to monitor gene- and cell-based therapies in human subjects. Potential immunogenicity of current viral transgenes warrants development of human-based reporter systems. We compared human nucleoside kinase reporters to a panel of nucleoside analogs of FEAU, FMAU, and FIAU, including the first in vivo assessment of L-[18F]FEAU.ProceduresHuman isogenic U87 cell lines were transduced to express different human reporter genes including dCK-R104M/D133A (dCKDM), dCK-R104Q/D133N (dCKep16A), dCK-A100V/R104M/D133A (dCK3M), and&nbsp;TK2-N93D/L109F (TK2DM), and wild-type dCK (dCK) and herpes simplex virus type-1 (HSVTK) reporter gene as references. In vitro cell uptake assays were performed with [18F]FEAU, L-[18F]FEAU, [14C]FMAU, L-[18F]FMAU, and [124I]FIAU. Micro-positron emission tomography/X-ray computed tomography imaging of xenograft-bearing nu/nu mice was conducted with [18F]FEAU, L-[18F]FEAU, L-[18F]FMAU, and [124I]FIAU on consecutive days. A cell viability assay was also performed to assess sensitivities to gemcitabine and bromovinyldeoxyuridine (BVdU).ResultsIn vitro, dCKep16A and dCKDM with [18F]FEAU exhibited the highest sensitivity and selectivity of the human reporters, second only to HSVTK/[18F]FEAU. L-[18F]FEAU biodistribution in mice was on par with [18F]FEAU and L-[18F]FMAU. L-[18F]FMAU uptake in isogenic xenografts was highest for all human reporter genes. However, [18F]FEAU was the most selective of the short half-life reporter probes due to its minimal recognition by human dCK and relative sensitivity, whereas [124I]FIAU permitted imaging at a later time point, improving signal-to-background ratio. Of the human reporter genes, dCKep16A consistently outperformed the&nbsp;other tested reporters. Reporter genes of interest increased potency to the nucleoside analog prodrugs gemcitabine and BVdU.ConclusionsWe demonstrate that human nucleoside kinase reporter systems vary significantly in their sensitivity and selectivity for in vivo imaging. The sufficiently high signal-to-background ratios and enhanced suicide gene potential support clinical translation

Abstract 2894: XMT-1592, a site-specific Dolasynthen-based NaPi2b-targeted antibody-drug conjugate for the treatment of ovarian cancer and lung adenocarcinoma

Abstract The Dolasynthen platform incorporates the highly potent anti-mitotic agent auristatin F-HPA (AF-HPA), with its associated DolaLock mechanism of controlled bystander effect, and enables the synthesis of antibody-drug conjugates (ADCs) with precise control of the drug-to-antibody ratio (DAR) and site-specific bioconjugation. XMT-1592 is a novel ADC comprised of an anti-NaPi2b antibody and Dolasynthen, conjugated in a site-specific manner to yield DAR 6. NaPi2b, also known as SLC34A2, is a transmembrane sodium-phosphate transporter that is broadly expressed on tumor cells in ovarian carcinoma, NSCLC lung adenocarcinoma and other tumor types. Recent studies have shown that NaPi2b expression is enriched in the EGFR and KRAS mutant subtypes of lung adenocarcinoma. Binding studies showed a specific, high-affinity interaction of XMT-1592 with NaPi2b that was not affected by conjugated Dolasynthen. XMT-1592 elicited potent and specific in vitro cytotoxicity against NaPi2b-expressing ovarian carcinoma cells. XMT-1592 exhibited potent and specific in vivo activity in NaPi2b-expressing tumor xenografts derived from ovarian carcinoma or lung adenocarcinoma. Consistent with the targeted delivery benefits of the ADC approach, XMT-1592 yielded high and sustained concentrations of AF-HPA to tumors but not normal tissues. To evaluate the benefits of site-specific bioconjugation of Dolasynthen, we conducted in vitro and in vivo comparisons of XMT-1592 to a stochastically conjugated version of the ADC. XMT-1592 had improved in vivo activity, pharmacokinetics, and clinical pathology relative to its stochastic counterpart. Taken together, these results support XMT-1592 as a development candidate for the treatment of NaPi2b-expressing tumors. Citation Format: Shawn Fessler, Anouk Dirksen, Scott D. Collins, Ling Xu, Winnie Lee, Jason Wang, Ron Eydelloth, Elena Ter-Ovanesyen, Jeffrey Zurita, Elizabeth Ditty, Barrett Nehilla, Susan Clardy, Susan Clardy, Tyler Carter, Kenneth Avocetien, Mark Nazzaro, Nam Le, Kalli C. Catcott, Alex Uttard, Bingfan Du, Chen-Ni Chin, Rebecca Mosher, Kelly Slocum, Liuliang Qin, David Lee, Dorin Toader, Marc Damelin, Timothy B. Lowinger. XMT-1592, a site-specific Dolasynthen-based NaPi2b-targeted antibody-drug conjugate for the treatment of ovarian cancer and lung adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 2894