The rapid evolution of the central star of the Stingray Nebula - latest news from the HST

SAO 244567 is an unusually fast evolving star. Within twenty years only, it had turned from a B-type supergiant into the central star of the Stingray Nebula. Space- and ground-based observations obtained over the last decades have revealed that its spectrum changes noticeably over just a few years, showing stellar evolution in real time. The low mass of SAO 244567 is, however, in strong contradiction with canonical post-asymptotic giant branch evolution. Thus, its fast evolution has been a mystery for decades. We present preliminary results of the non-LTE spectral analyis of the recently obtained HST/COS observations, which finally allow us to shed light on the evolutionary history of this extraordinary object.Facultad de Ciencias Astronómicas y GeofísicasInstituto de Astrofísica de La Plat

The photospheres of the hottest fastest stars in the Galaxy

We perform nonlocal thermodynamic equilibrium (NLTE) model atmosphere analyses of the three hottest hypervelocity stars (space velocities between $\approx$ 1500-2800 km s$^{-1}$) known to date, which were recently discovered spectroscopically and identified as runaways from Type Ia supernovae. The hottest of the three (J0546$+$0836, effective temperature $T_\mathrm{eff}$ = 95,000 $\pm$ 15,000 K, surface gravity log g = $5.5 \pm 0.5$) has an oxygen-dominated atmosphere with a significant amount of carbon (C = $0.10 \pm 0.05$, O = $0.90 \pm 0.05$, mass fractions). Its mixed absorption+emission line spectrum exhibits photospheric absorption lines from O V and O VI as well as O III and O IV emission lines that are formed in a radiation-driven wind with a mass-loss rate of the order of $10^{-8}$ $M_\odot$ yr$^{-1}$. Spectroscopically, J0546$+$0836 is a [WC]-PG1159 transition-type pre-white dwarf. The second object (J0927$-$6335) is a PG1159-type white dwarf with a pure absorption-line spectrum dominated by C III/C IV and O III/O IV. We find $T_\mathrm{eff}$ = 60,000 $\pm$ 5000 K, log g = $7.0 \pm 0.5$, and a carbon- and oxygen-dominated atmosphere with C = $0.47 \pm 0.25$, O = $0.48 \pm 0.25$, and possibly a minute amount of helium (He = $0.05 \pm 0.05$). Comparison with post-AGB evolutionary tracks suggests a mass of $M\approx0.5$ $M_\odot$ for both objects, if such tracks can safely be applied to these stars. We find the third object (J1332$-$3541) to be a relatively massive ($M=0.89 M_\odot$) hydrogen-rich (DAO) white dwarf with $T_\mathrm{eff}$ = 65,657 $\pm$ 2390 K, log g = $8.38 \pm 0.08$, and abundances H = $0.65 \pm 0.04$ and He = $0.35 \pm 0.04$. We discuss our results in the context of the "dynamically driven double-degenerate double-detonation" (D$^6$) scenario proposed for the origin of these stars.Comment: Accepted for publication in A&

Analysis of the Proteolytic Processing of ABCA3: Identification of Cleavage Site and Involved Proteases

Rationale ABCA3 is a lipid transporter in the limiting membrane of lamellar bodies in alveolar type II cells. Mutations in the ABCA3 gene cause respiratory distress syndrome in new-borns and childhood interstitial lung disease. ABCA3 is N-terminally cleaved by an as yet unknown protease, a process believed to regulate ABCA3 activity. Methods The exact site where ABCA3 is cleaved was localized using mass spectrometry (MS). Proteases involved in ABCA3 processing were identified using small molecule inhibitors and siRNA mediated gene knockdown. Results were verified by in vitro digestion of a synthetic peptide substrate mimicking ABCA3's cleavage region, followed by MS analysis. Results We found that cleavage of ABCA3 occurs after Lys174 which is located in the proteins' first luminal loop. Inhibition of cathepsin L and, to a lesser extent, cathepsin B resulted in attenuation of ABCA3 cleavage. Both enzymes showed activity against the ABCA3 peptide in vitro with cathepsin L being more active. Conclusion We show here that, like some other proteins of the lysosomal membrane, ABCA3 is a substrate of cathepsin L. Therefore, cathepsin L may represent a potential target to therapeutically influence ABCA3 activity in ABCA3-associated lung disease

The photospheres of the hottest fastest stars in the Galaxy

We perform nonlocal thermodynamic equilibrium (NLTE) model atmosphere analyses of the three hottest hypervelocity stars (space velocities between ≈1500–2800 km s−1) known to date, which were recently discovered spectroscopically and identified as runaways from Type Ia supernovae. The hottest of the three (J0546+0836, effective temperature Teff = 95 000 ± 15 000 K, surface gravity lo

Highly conserved serine residue 40 in HIV-1 p6 regulates capsid processing and virus core assembly

Background: The HIV-1 p6 Gag protein regulates the final abscission step of nascent virions from the cell membrane by the action of two late assembly (L-) domains. Although p6 is located within one of the most polymorphic regions of the HIV-1 gag gene, the 52 amino acid peptide binds at least to two cellular budding factors (Tsg101 and ALIX), is a substrate for phosphorylation, ubiquitination, and sumoylation, and mediates the incorporation of the HIV-1 accessory protein Vpr into viral particles. As expected, known functional domains mostly overlap with several conserved residues in p6. In this study, we investigated the importance of the highly conserved serine residue at position 40, which until now has not been assigned to any known function of p6. Results: Consistently with previous data, we found that mutation of Ser-40 has no effect on ALIX mediated rescue of HIV-1 L-domain mutants. However, the only feasible S40F mutation that preserves the overlapping pol open reading frame (ORF) reduces virus replication in T-cell lines and in human lymphocyte tissue cultivated ex vivo. Most intriguingly, L-domain mediated virus release is not dependent on the integrity of Ser-40. However, the S40F mutation significantly reduces the specific infectivity of released virions. Further, it was observed that mutation of Ser-40 selectively interferes with the cleavage between capsid (CA) and the spacer peptide SP1 in Gag, without affecting cleavage of other Gag products. This deficiency in processing of CA, in consequence, led to an irregular morphology of the virus core and the formation of an electron dense extra core structure. Moreover, the defects induced by the S40F mutation in p6 can be rescued by the A1V mutation in SP1 that generally enhances processing of the CA-SP1 cleavage site. Conclusions: Overall, these data support a so far unrecognized function of p6 mediated by Ser-40 that occurs independently of the L-domain function, but selectively affects CA maturation and virus core formation, and consequently the infectivity of released virions

Wetting of metals and glasses on Mo

The wetting of low melting point metals and Si-Ca-Al-Ti-O glasses on molybdenum has been investigated. The selected metals (Au, Cu, Ag) form a simple eutectic with Mo. Metal spreading occurs under nonreactive conditions without interdiffusion or ridge formation. The metals exhibit low (non-zero) contact angles on Mo but this requires temperatures higher than 1100 C in reducing atmospheres in order to eliminate a layer of adsorbed impurities on the molybdenum surface. By controlling the oxygen activity in the furnace, glass spreading can take place under reactive or nonreactive conditions. We have found that in the glass/Mo system the contact angle does not decrease under reactive conditions. In all cases, adsorption from the liquid seems to accelerate the diffusivity on the free molybdenum surface

Returning Individual Research Results from Digital Phenotyping in Psychiatry

Psychiatry is rapidly adopting digital phenotyping and artificial intelligence/machine learning tools to study mental illness based on tracking participants’ locations, online activity, phone and text message usage, heart rate, sleep, physical activity, and more. Existing ethical frameworks for return of individual research results (IRRs) are inadequate to guide researchers for when, if, and how to return this unprecedented number of potentially sensitive results about each participant’s real-world behavior. To address this gap, we convened an interdisciplinary expert working group, supported by a National Institute of Mental Health grant. Building on established guidelines and the emerging norm of returning results in participant-centered research, we present a novel framework specific to the ethical, legal, and social implications of returning IRRs in digital phenotyping research. Our framework offers researchers, clinicians, and Institutional Review Boards (IRBs) urgently needed guidance, and the principles developed here in the context of psychiatry will be readily adaptable to other therapeutic areas

Subcutaneous vs Intravenous Trastuzumab/Pertuzumab: A Time and Motion Substudy of a Phase II Trial of Adjuvant Trastuzumab/Pertuzumab for Stage I HER2+ Breast Cancer (ADEPT trial).

PURPOSE: The time required for in-clinic drug administration can substantially affect breast cancer patients' quality of life. Subcutaneous (SC) drug administration, as opposed to intravenous (IV), may reduce this time commitment. This study sought to estimate the difference in time burden between IV and SC administration of trastuzumab and pertuzumab (HP). METHODS: We prospectively enrolled a subcohort of patients participating in the ADEPT trial (ClinicalTrials.gov identifier: NCT04569747, investigating adjuvant HP plus endocrine therapy for stage I human epidermal growth factor receptor 2-positive breast cancer) to this single-arm crossover time and motion substudy. Patients received two cycles of IV HP followed by two cycles of SC HP. During each cycle, time points in drug preparation and administration were captured. The primary end point was total patient time in the treatment chair. Additional end points included total patient treatment experience time and total pharmacy workflow time. A sample size of 22 patients was estimated to provide 90.7% power with two-sided alpha .05 to detect a difference of 70 minutes in the primary end point by treatment arm (IV v SC). RESULTS: Twenty-two patients were enrolled. The mean total patient time in the treatment chair was 61.8 minutes shorter with SC versus IV HP (22.5 v 84.3 minutes; P < .0001). The mean total patient treatment experience time (incorporating time spent waiting for treatment initiation and time spent in the treatment chair) was 81.8 minutes shorter for SC administration (96 v 177.8 minutes; P < .0001). The pharmacy workflow time was 78.2 minutes shorter for SC versus IV formulation (41 v 119.2 minutes; P < .0001). CONCLUSION: SC administration of HP shortened patient time burden by approximately 1 hour. SC drug administration can facilitate faster workflows for health care professionals and improve patients' breast cancer treatment experience

Use of cancer-specific yeast-secreted in vivo biotinylated recombinant antibodies for serum biomarker discovery

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