HOPS 361-C's Jet Decelerating and Precessing Through NGC 2071 IR

We present a two-epoch Hubble Space Telescope (HST) near-infrared (NIR) study of NGC 2071 IR highlighting HOPS 361-C, a protostar producing an arced 0.2 parsec-scale jet. Proper motions for the brightest knots decrease from 350 to 100 km/s with increasing distance from the source. The [Fe II] and Pa$\beta$ emission line intensity ratio gives a velocity jump through each knot of 40-50 km/s. We show a new [O I] 63 $\rm \mu$m spectrum taken with the German REciever for Astronomy at Terahertz frequencies (GREAT) instrument aboard Stratospheric Observatory for Infrared Astronomy (SOFIA), which give a low jet inclination. Proper motions and jump velocities then estimate total flow speed throughout the jet. We model knot positions and speeds with a precessing jet that decelerates within the host molecular cloud. The measurements are matched with a precession period of a few thousand years and half opening angle of 15$\rm\deg$. The [Fe II] 1.26 $\rm \mu$m to 1.64 $\rm \mu$m line intensity ratio gives the extinction to each knot ranging from 5-30 mag. Relative to $\sim$14 mag of extinction through the cloud from C$^{18}$O emission maps, the jet is well embedded at a fractional depth from 1/5 to 4/5, and can interact with the cloud. Our model suggests the jet is locally dissipated over 0.2 pc. This may be because knots sweep through a wide angle, giving the cloud time to fill in cavities opened by the jet. This contrasts with nearly unidirectional protostellar jets that puncture host clouds and can propagate significantly further than a quarter pc.Comment: 24 pages, 9 figures, submitted to Ap

Giving is a question of time: Response times and contributions to a real world public good

Recent experimental research has examined whether contributions to public goods can be traced back to intuitive or deliberative decision-making, using response times in public good games in order to identify the specific decision process at work. In light of conflicting results, this paper reports on an analysis of response time data from an online experiment in which over 3400 subjects from the general population decided whether to contribute to a real world public good. The between-subjects evidence confirms a strong positive link between contributing and deliberation and between free-riding and intuition. The average response time of contributors is 40 percent higher than that of free-riders. A within-subject analysis reveals that for a given individual, contributing significantly increases and free-riding significantly decreases the amount of deliberation required

Whole-Exome sequencing analysis identified TMSB10/TRABD2A locus to be associated with carfilzomib-related cardiotoxicity among patients with multiple myeloma

BackgroundProteasome inhibitor Carfilzomib (CFZ) is effective in treating patients with refractory or relapsed multiple myeloma (MM) but has been associated with cardiovascular adverse events (CVAE) such as hypertension, cardiomyopathy, and heart failure. This study aimed to investigate the contribution of germline genetic variants in protein-coding genes in CFZ-CVAE among MM patients using whole-exome sequencing (WES) analysis.MethodsExome-wide single-variant association analysis, gene-based analysis, and rare variant analyses were performed on 603,920 variants in 247 patients with MM who have been treated with CFZ and enrolled in the Oncology Research Information Exchange Network (ORIEN) at the Moffitt Cancer Center. Separate analyses were performed in European Americans and African Americans followed by a trans-ethnic meta-analysis.ResultsThe most significant variant in the exome-wide single variant analysis was a missense variant rs7148 in the thymosin beta-10/TraB Domain Containing 2A (TMSB10/TRABD2A) locus. The effect allele of rs7148 was associated with a higher risk of CVAE [odds ratio (OR) = 9.3 with a 95% confidence interval of 3.9—22.3, p = 5.42*10−7]. MM patients with rs7148 AG or AA genotype had a higher risk of CVAE (50%) than those with GG genotype (10%). rs7148 is an expression quantitative trait locus (eQTL) for TRABD2A and TMSB10. The gene-based analysis also showed TRABD2A as the most significant gene associated with CFZ-CVAE (p = 1.06*10−6).ConclusionsWe identified a missense SNP rs7148 in the TMSB10/TRABD2A as associated with CFZ-CVAE in MM patients. More investigation is needed to understand the underlying mechanisms of these associations

Investigating Protostellar Accretion-Driven Outflows Across the Mass Spectrum: JWST NIRSpec IFU 3-5~μ\mum Spectral Mapping of Five Young Protostars

Investigating Protostellar Accretion (IPA) is a Cycle 1 JWST program using the NIRSpec+MIRI IFUs to obtain 2.9--28 $\mu$m spectral cubes of five young protostars with luminosities of 0.2 to 10,000 L$_{\odot}$ in their primary accretion phase. This paper introduces the NIRSpec 2.9--5.3 $\mu$m data of the inner 840-9000 au with spatial resolutions from 28-300 au. The spectra show rising continuum emission, deep ice absorption, emission from H$_{2}$, H~I, and [Fe~II], and the CO fundamental series in emission and absorption. Maps of the continuum emission show scattered light cavities for all five protostars. In the cavities, collimated jets are detected in [Fe~II] for the four $< 320$~L$_{\odot}$ protostars, two of which are additionally traced in Br-$\alpha$. Knots of [Fe~II] emission are detected toward the most luminous protostar, and knots of [FeII] emission with dynamical times of $< 30$~yrs are found in the jets of the others. While only one jet is traced in H$_2$, knots of H$_2$ and CO are detected in the jets of four protostars. H$_2$ is seen extending through the cavities showing they are filled by warm molecular gas. Bright H$_2$ emission is seen along the walls of a single cavity, while in three cavities, narrow shells of H$_2$ emission are found, one of which has an [Fe~II] knot at its apex. These data show cavities containing collimated jets traced in atomic/ionic gas surrounded by warm molecular gas in a wide-angle wind and/or gas accelerated by bow shocks in the jets.Comment: 30 pages, 11 figure

Breakthrough SARS-CoV-2 infections among patients with cancer following two and three doses of COVID-19 mRNA vaccines: a retrospective observational study from the COVID-19 and Cancer Consortium

BACKGROUND: Breakthrough SARS-CoV-2 infections following vaccination against COVID-19 are of international concern. Patients with cancer have been observed to have worse outcomes associated with COVID-19 during the pandemic. We sought to evaluate the clinical characteristics and outcomes of patients with cancer who developed breakthrough SARS-CoV-2 infections after 2 or 3 doses of mRNA vaccines. METHODS: We evaluated the clinical characteristics of patients with cancer who developed breakthrough infections using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19; NCT04354701). Analysis was restricted to patients with laboratory-confirmed SARS-CoV-2 diagnosed in 2021 or 2022, to allow for a contemporary unvaccinated control population; potential differences were evaluated using a multivariable logistic regression model after inverse probability of treatment weighting to adjust for potential baseline confounding variables. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) are reported. The primary endpoint was 30-day mortality, with key secondary endpoints of hospitalization and ICU and/or mechanical ventilation (ICU/MV). FINDINGS: The analysis included 2486 patients, of which 564 and 385 had received 2 or 3 doses of an mRNA vaccine prior to infection, respectively. Hematologic malignancies and recent receipt of systemic anti-neoplastic therapy were more frequent among vaccinated patients. Vaccination was associated with improved outcomes: in the primary analysis, 2 doses (aOR: 0.62, 95% CI: 0.44-0.88) and 3 doses (aOR: 0.20, 95% CI: 0.11-0.36) were associated with decreased 30-day mortality. There were similar findings for the key secondary endpoints of ICU/MV (aOR: 0.60, 95% CI: 0.45-0.82 and 0.37, 95% CI: 0.24-0.58) and hospitalization (aOR: 0.60, 95% CI: 0.48-0.75 and 0.35, 95% CI: 0.26-0.46) for 2 and 3 doses, respectively. Importantly, Black patients had higher rates of hospitalization (aOR: 1.47, 95% CI: 1.12-1.92), and Hispanic patients presented with higher rates of ICU/MV (aOR: 1.61, 95% CI: 1.06-2.44). INTERPRETATION: Vaccination against COVID-19, especially with additional doses, is a fundamental strategy in the prevention of adverse outcomes including death, among patients with cancer. FUNDING: This study was partly supported by grants from the National Cancer Institute grant number P30 CA068485 to C-YH, YS, SM, JLW; T32-CA236621 and P30-CA046592 to C.R.F; CTSA 2UL1TR001425-05A1 to TMW-D; ACS/FHI Real-World Data Impact Award, P50 MD017341-01, R21 CA242044-01A1, Susan G. Komen Leadership Grant Hunt to MKA. REDCap is developed and supported by Vanderbilt Institute for Clinical and Translational Research grant support (UL1 TR000445 from NCATS/NIH)

Imaging of Zebrafish In Vivo with Second-Harmonic Generation Reveals Shortened Sarcomeres Associated with Myopathy Induced by Statin

We employed second-harmonic generation (SHG) imaging and the zebrafish model to investigate the myopathy caused by statin in vivo with emphasis on the altered microstructures of the muscle sarcomere, the fundamental contractile element of muscles. This approach derives an advantage of SHG imaging to observe the striated skeletal muscle of living zebrafish based on signals produced mainly from the thick myosin filament of sarcomeres without employing exogenous labels, and eliminates concern about the distortion of muscle structures caused by sample preparation in conventional histological examination. The treatment with statin caused a significantly shortened sarcomere relative to an untreated control (1.73±0.09 µm vs 1.91±0.08 µm, P<0.05) while the morphological integrity of the muscle fibers remained largely intact. Mechanistic tests indicated that this microstructural disorder was associated with the biosynthetic pathway of cholesterol, or, specifically, with the impaired production of mevalonate by statins. This microstructural disorder exhibited a strong dependence on both the dosage and the duration of treatment, indicating a possibility to assess the severity of muscle injury according to the altered length of the sarcomeres. In contrast to a conventional assessment of muscle injury using clinical biomarkers in blood, such as creatine kinase that is released from only disrupted myocytes, the ability to determine microstructural modification of sarcomeres allows diagnosis of muscle injury before an onset of conventional clinical symptoms. In light of the increasing prevalence of the incidence of muscle injuries caused by new therapies, our work consolidates the combined use of the zebrafish and SHG imaging as an effective and sensitive means to evaluate the safety profile of new therapeutic targets in vivo

Approximate policy iteration: A survey and some new methods

We consider the classical policy iteration method of dynamic programming (DP), where approximations and simulation are used to deal with the curse of dimensionality. We survey a number of issues: convergence and rate of convergence of approximate policy evaluation methods, singularity and susceptibility to simulation noise of policy evaluation, exploration issues, constrained and enhanced policy iteration, policy oscillation and chattering, and optimistic and distributed policy iteration. Our discussion of policy evaluation is couched in general terms and aims to unify the available methods in the light of recent research developments and to compare the two main policy evaluation approaches: projected equations and temporal differences (TD), and aggregation. In the context of these approaches, we survey two different types of simulation-based algorithms: matrix inversion methods, such as least-squares temporal difference (LSTD), and iterative methods, such as least-squares policy evaluation (LSPE) and TD (λ), and their scaled variants. We discuss a recent method, based on regression and regularization, which rectifies the unreliability of LSTD for nearly singular projected Bellman equations. An iterative version of this method belongs to the LSPE class of methods and provides the connecting link between LSTD and LSPE. Our discussion of policy improvement focuses on the role of policy oscillation and its effect on performance guarantees. We illustrate that policy evaluation when done by the projected equation/TD approach may lead to policy oscillation, but when done by aggregation it does not. This implies better error bounds and more regular performance for aggregation, at the expense of some loss of generality in cost function representation capability. Hard aggregation provides the connecting link between projected equation/TD-based and aggregation-based policy evaluation, and is characterized by favorable error bounds.National Science Foundation (U.S.) (No.ECCS-0801549)Los Alamos National Laboratory. Information Science and Technology InstituteUnited States. Air Force (No.FA9550-10-1-0412