H2 formation and excitation in the diffuse interstellar medium

We use far-UV absorption spectra obtained with FUSE towards three late B stars to study the formation and excitation of H2 in the diffuse ISM. The data interpretation relies on a model of the chemical and thermal balance in photon-illuminated gas. The data constrain well the nR product between gas density and H2 formation rate on dust grains: nR = 1 to 2.2 e-15 s-1. For each line of sight the mean effective H2 density n, assumed uniform, is obtained by the best fit of the model to the observed N(J=1)/N(J=0) ratio, since the radiation field is known. Combining n with the nR values, we find similar H2 formation rates for the three stars of about R = 4 e-17 cm3/s. Because the target stars do not interact with the absorbing matter we can show that the H2 excitation in the J>2 levels cannot be accounted for by the UV pumping of the cold H2 but implies collisional excitation in regions where the gas is much warmer. The existence of warm H2 is corroborated by the fact that the star with the largest column density of CH+ has the largest amount of warm H2.Comment: 7 pages, 4 figures, to be published in Astronomy & Astrophysic

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570

Far to near UV spectroscopy of the interstellar medium at very high resolution and very high signal-to-noise ratio

Science white paper submitted to the Astro2020 Decadal SurveyA comprehensive study of interstellar medium phases and the nature of their boundaries or connections requires comparing abundances and velocity profiles from tracers of the different phases. In the UV, studies of a wealth of absorption features appearing in the spectra of hot stars yield fundamental insights into the composition and physical characteristics of all phases of the ISM along with the processes that influence them. They also inform us on the nature of boundaries between them. However no single instrument has as yet given access to species in all ISM phases at the same high spectral resolution: from the molecular bands of CO and H2 in the far-UV, to the cold neutral medium tracers C I and S I and the warm medium tracers like C II, NI, OI, Mg II, Fe II, Si II etc, and to the high ions of the hot ionized medium C IV, Si IV in the UV, as well as O VI in the far UV. We have yet to design the spectrometer that will enable observing the full UV domain at resolving power R>200 000 and signal-to-noise ratio SNR>500. The line FWHM being governed by turbulence, temperature, and species mass, such a resolution is necessary to resolve lines from both the cold molecular hydrogen and the warm metal ions with a turbulence of ~1 km/s, and to differentiate distinct velocity components, typically separated by less than 2 km/s

Far to near UV spectroscopy of the interstellar medium at very high resolution and very high signal-to-noise ratio

Science white paper submitted to the Astro2020 Decadal SurveyA comprehensive study of interstellar medium phases and the nature of their boundaries or connections requires comparing abundances and velocity profiles from tracers of the different phases. In the UV, studies of a wealth of absorption features appearing in the spectra of hot stars yield fundamental insights into the composition and physical characteristics of all phases of the ISM along with the processes that influence them. They also inform us on the nature of boundaries between them. However no single instrument has as yet given access to species in all ISM phases at the same high spectral resolution: from the molecular bands of CO and H2 in the far-UV, to the cold neutral medium tracers C I and S I and the warm medium tracers like C II, NI, OI, Mg II, Fe II, Si II etc, and to the high ions of the hot ionized medium C IV, Si IV in the UV, as well as O VI in the far UV. We have yet to design the spectrometer that will enable observing the full UV domain at resolving power R>200 000 and signal-to-noise ratio SNR>500. The line FWHM being governed by turbulence, temperature, and species mass, such a resolution is necessary to resolve lines from both the cold molecular hydrogen and the warm metal ions with a turbulence of ~1 km/s, and to differentiate distinct velocity components, typically separated by less than 2 km/s

Magnetic tagging of cell-derived microparticles: new prospects for imaging and manipulation of these mediators of biological information

Aims: Submicron membrane fragments termed microparticles (MPs), which are released by apoptotic or activated cells, are newly considered as vectors of biological information and actors of pathology development. We propose the tagging of MPs with magnetic nanoparticles as a new approach allowing imaging, manipulation and targeting of cell-derived MPs. Materials & methods: MPs generated in vitro from human endothelial cells or isolated from atherosclerotic plaques were labeled using citrate-coated 8 nm iron-oxide nanoparticles. MPs were tagged with magnetic nanoparticles on their surface and detected as Annexin-V positive by flow cytometry. Results: Labeled MPs could be mobilized, isolated and manipulated at a distance in a magnetic field gradient. Magnetic mobility of labeled MPs was quantified by micromagnetophoresis. Interactions of labeled MPs with endothelial cells could be triggered and modulated by magnetic guidance. Nanoparticles served as tracers at different scales: at the subcellular level by electron microscopy, at the cellular level by histology and at the macroscopic level by MRI. Conclusion: Magnetic labeling of biogenic MPs opens new prospects for noninvasive monitoring and distal manipulations of these biological effectors

Shear Stress Regulates Endothelial Microparticle Release

International audienceRationale: Endothelial activation and apoptosis release membrane-shed microparticles (EMP) that emerge as important biological effectors. Objective: Because laminar shear stress (SS) is a major physiological regulator of endothelial survival, we tested the hypothesis that SS regulates EMP release. Methods and Results: EMP levels were quantified by flow cytometry in medium of endothelial cells subjected to low or high SS (2 and 20 dyne/cm 2 ). EMP levels augmented with time in low SS conditions compared with high SS conditions. This effect was sensitive to extracellular signal-regulated protein kinases 1 and 2 (ERK1/2) and Rho kinases inhibitors but unaffected by caspase inhibitors. Low SS-stimulated EMP release was associated with increased endothelial Rho kinases and ERK1/2 activities and cytoskeletal reorganization. Overexpression of constitutively active RhoA stimulated EMP release under high SS. We also examined the effect of nitric oxide (NO) in mediating SS effects. L-NG-nitroarginine methyl ester (L-NAME), but not D-NG-nitroarginine methyl ester, increased high SS-induced EMP levels by 3-fold, whereas the NO donor S-nitroso-N-acetyl-D,L-penicillamine (SNAP) decreased it. L-NAME and SNAP did not affect Rho kinases and ERK1/2 activities. Then, we investigated NO effect on membrane remodeling because microparticle release is abolished in ABCA1-deficient cells. ABCA1 expression, which was greater under low SS than under high SS, was augmented by L-NAME under high SS and decreased by SNAP under low SS conditions. Conclusions: Altogether, these results demonstrate that sustained atheroprone low SS stimulates EMP release through activation of Rho kinases and ERK1/2 pathways, whereas atheroprotective high SS limits EMP release in a NO-dependent regulation of ABCA1 expression and of cytoskeletal reorganization. These findings, therefore, identify endothelial SS as a physiological regulator of microparticle release