The Herschel-Heterodyne Instrument for the Far-Infrared (HIFI): instrument and pre-launch testing

This paper describes the Heterodyne Instrument for the Far-Infrared (HIFI), to be launched onboard of ESA's Herschel Space Observatory, by 2008. It includes the first results from the instrument level tests. The instrument is designed to be electronically tuneable over a wide and continuous frequency range in the Far Infrared, with velocity resolutions better than 0.1 km/s with a high sensitivity. This will enable detailed investigations of a wide variety of astronomical sources, ranging from solar system objects, star formation regions to nuclei of galaxies. The instrument comprises 5 frequency bands covering 480-1150 GHz with SIS mixers and a sixth dual frequency band, for the 1410-1910 GHz range, with Hot Electron Bolometer Mixers (HEB). The Local Oscillator (LO) subsystem consists of a dedicated Ka-band synthesizer followed by 7 times 2 chains of frequency multipliers, 2 chains for each frequency band. A pair of Auto-Correlators and a pair of Acousto-Optic spectrometers process the two IF signals from the dual-polarization front-ends to provide instantaneous frequency coverage of 4 GHz, with a set of resolutions (140 kHz to 1 MHz), better than < 0.1 km/s. After a successful qualification program, the flight instrument was delivered and entered the testing phase at satellite level. We will also report on the pre-flight test and calibration results together with the expected in-flight performance

MICROSCOPE mission: first results of a space test of the equivalence principle

According to the weak equivalence principle, all bodies should fall at the same rate in a gravitational field. The MICROSCOPE satellite, launched in April 2016, aims to test its validity at the 10−15 precision level, by measuring the force required to maintain two test masses (of titanium and platinum alloys) exactly in the same orbit. A nonvanishing result would correspond to a violation of the equivalence principle, or to the discovery of a new long-range force. Analysis of the first data gives δ(Ti,Pt)=[−1±9(stat)±9(syst)]×10−15 (1σ statistical uncertainty) for the titanium-platinum Eötvös parameter characterizing the relative difference in their free-fall accelerations

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

Industries du Cuir. Les peaux des bovides col niaux. Lettre-preface de G. Angoulvant.

Paris, Emile Larose, 191

Preparation and in vitro/in vivo evaluation of nano-sized crystals for dissolution rate enhancement of ucb-35440-3, a highly dosed poorly water-soluble weak base

ucb-35440-3 is a new drug entity under investigation at UCB S.A. Due to its physicochemical characteristics, the drug, a poorly water-soluble weak base, shows poor solubility and dissolution characteristics. In rat, the low oral bioavailability (F < 10%) is largely due to poor absorption. In order to enhance the solubility and dissolution characteristics, formulation of ucb-35440-3 as nanocrystals has been achieved in this study. Nanoparticles were prepared using high pressure homogenization and were characterized in terms of size and morphology. In vitro dissolution characteristics were investigated and compared to the un-milled drug in order to verify the theoretical hypothesis on the benefit of increased surface area. In vivo pharmacokinetic evaluation of ucb-35440-3 nanoparticles was also carried out on rats. Crystalline state evaluation before and following particle size reduction was conducted through polarized light microscopy and PXRD to denote any possible transformation to an amorphous state during the homogenization process. Drug chemical stability was also assessed following homogenization. The dissolution rate increased significantly at pH 3.0, 5.0 and 6.5 for ucb-35440-3 nanoparticles. However, the pharmacokinetic profile obtained yielded lower systemic exposure than the un-milled compound (in fed state), this although being thought to be the consequence of the drug and formulation characteristics. © 2006 Elsevier B.V. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Optimal matching of 3-D convex polyhedra

SIGLECNRS RP 207 (206) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

L'Antiquité dévoilée par ses usages, ou Examen critique des principales opinions, cérémonies & institutions religieuses & politiques des différens peuples de la terre. Tome 2 / . Par feu M. Boulanger. Tome premier [-troisieme].

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