Post-transplant cyclophosphamide prevents xenogeneic graft-versus-host disease while depleting proliferating regulatory T cells

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Quantum cascade laser frequency stabilisation at the sub-Hz level

Quantum Cascade Lasers (QCL) are increasingly being used to probe the mid-infrared "molecular fingerprint" region. This prompted efforts towards improving their spectral performance, in order to reach ever-higher resolution and precision. Here, we report the stabilisation of a QCL onto an optical frequency comb. We demonstrate a relative stability and accuracy of 2x10-15 and 10-14, respectively. The comb is stabilised to a remote near-infrared ultra-stable laser referenced to frequency primary standards, whose signal is transferred via an optical fibre link. The stability and frequency traceability of our QCL exceed those demonstrated so far by two orders of magnitude. As a demonstration of its capability, we then use it to perform high-resolution molecular spectroscopy. We measure absorption frequencies with an 8x10-13 relative uncertainty. This confirms the potential of this setup for ultra-high precision measurements with molecules, such as our ongoing effort towards testing the parity symmetry by probing chiral species

Altimetry for the future: Building on 25 years of progress

In 2018 we celebrated 25 years of development of radar altimetry, and the progress achieved by this methodology in the fields of global and coastal oceanography, hydrology, geodesy and cryospheric sciences. Many symbolic major events have celebrated these developments, e.g., in Venice, Italy, the 15th (2006) and 20th (2012) years of progress and more recently, in 2018, in Ponta Delgada, Portugal, 25 Years of Progress in Radar Altimetry. On this latter occasion it was decided to collect contributions of scientists, engineers and managers involved in the worldwide altimetry community to depict the state of altimetry and propose recommendations for the altimetry of the future. This paper summarizes contributions and recommendations that were collected and provides guidance for future mission design, research activities, and sustainable operational radar altimetry data exploitation. Recommendations provided are fundamental for optimizing further scientific and operational advances of oceanographic observations by altimetry, including requirements for spatial and temporal resolution of altimetric measurements, their accuracy and continuity. There are also new challenges and new openings mentioned in the paper that are particularly crucial for observations at higher latitudes, for coastal oceanography, for cryospheric studies and for hydrology. The paper starts with a general introduction followed by a section on Earth System Science including Ocean Dynamics, Sea Level, the Coastal Ocean, Hydrology, the Cryosphere and Polar Oceans and the ‘‘Green” Ocean, extending the frontier from biogeochemistry to marine ecology. Applications are described in a subsequent section, which covers Operational Oceanography, Weather, Hurricane Wave and Wind Forecasting, Climate projection. Instruments’ development and satellite missions’ evolutions are described in a fourth section. A fifth section covers the key observations that altimeters provide and their potential complements, from other Earth observation measurements to in situ data. Section 6 identifies the data and methods and provides some accuracy and resolution requirements for the wet tropospheric correction, the orbit and other geodetic requirements, the Mean Sea Surface, Geoid and Mean Dynamic Topography, Calibration and Validation, data accuracy, data access and handling (including the DUACS system). Section 7 brings a transversal view on scales, integration, artificial intelligence, and capacity building (education and training). Section 8 reviews the programmatic issues followed by a conclusion

Extracorporeal Membrane Oxygenation for Severe Acute Respiratory Distress Syndrome associated with COVID-19: An Emulated Target Trial Analysis.

RATIONALE: Whether COVID patients may benefit from extracorporeal membrane oxygenation (ECMO) compared with conventional invasive mechanical ventilation (IMV) remains unknown. OBJECTIVES: To estimate the effect of ECMO on 90-Day mortality vs IMV only Methods: Among 4,244 critically ill adult patients with COVID-19 included in a multicenter cohort study, we emulated a target trial comparing the treatment strategies of initiating ECMO vs. no ECMO within 7 days of IMV in patients with severe acute respiratory distress syndrome (PaO2/FiO2 <80 or PaCO2 ≥60 mmHg). We controlled for confounding using a multivariable Cox model based on predefined variables. MAIN RESULTS: 1,235 patients met the full eligibility criteria for the emulated trial, among whom 164 patients initiated ECMO. The ECMO strategy had a higher survival probability at Day-7 from the onset of eligibility criteria (87% vs 83%, risk difference: 4%, 95% CI 0;9%) which decreased during follow-up (survival at Day-90: 63% vs 65%, risk difference: -2%, 95% CI -10;5%). However, ECMO was associated with higher survival when performed in high-volume ECMO centers or in regions where a specific ECMO network organization was set up to handle high demand, and when initiated within the first 4 days of MV and in profoundly hypoxemic patients. CONCLUSIONS: In an emulated trial based on a nationwide COVID-19 cohort, we found differential survival over time of an ECMO compared with a no-ECMO strategy. However, ECMO was consistently associated with better outcomes when performed in high-volume centers and in regions with ECMO capacities specifically organized to handle high demand. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/)

Analyse de deux stratégies de différenciation des précurseurs d' oligodendrocytes (inhibition pharmacologique de la voie de signalisation Notch et étude du rôle du facteur de transcription Glial Cells Missing)

La sclérose en plaque (SEP) touche principalement l adulte jeune et se caractérise par une forte inflammation conduisant à la destruction des gaines de myéline et des oligodendrocytes. L un des enjeux thérapeutiques majeurs dans la SEP est de réussir à régénérer la myéline afin de préserver les axones et de rétablir la conduction de l influx nerveux. Au cours de ma thèse, je me suis intéressé à la molécule TFA-12. Cette molécule a été utilisée in vitro dans des cultures d OPCs où j ai pu mettre en évidence sa capacité à favoriser leur différenciation, en inhibant la voie de signalisation Notch. Cette voie de signalisation étant réactivée dans les lésions de SEP et dans son modèle animal l EAE (encéphalomyélite autoimmune expérimentale), j ai ensuite utilisé cette molécule en traitement dans des séries de souris atteintes d EAE. Le traitement par TFA-12 de souris EAE réduit significativement l évolution de la maladie. L analyse histologique montre une réduction des différentes composantes de cette pathologie telles que l inflammation, l astrogliose, l activation microgliale et le dommage axonal. Par ailleurs, nos données indiquent que TFA-12 a un effet bénéfique sur la différenciation des OPCs in vivo. La seconde partie de ma thèse a été consacrée à l étude de la fonction du gène Gcm1 chez la souris. Chez la drosophile, Gcm est un gène clé dont l expression dans les précurseurs neuraux détermine l orientation de leur différenciation vers une voie gliale. Deux homologues de Gcm ont été identifiés chez les mammifères : Gcm1 et Gcm2. La souris déficiente pour Gcm1 est létale dans les premiers stades de développement embryonnaire par défaut de placentation, ne permettant pas l étude du développement du SNC. Mon travail a porté sur l étude des effets de l expression ectopique de Gcm1 dans le SNC de la souris. J ai mis en évidence une accélération de la genèse des oligodendrocytes qui a pour conséquence une accélération de la myélinisation au stade post-natal.PARIS-BIUSJ-Thèses (751052125) / SudocPARIS-BIUSJ-Physique recherche (751052113) / SudocSudocFranceF

Le jeu : un outil pédagogique au service des apprentissages en mathématiques

The game is a very wide-spread educational tool in cycle 1 to the elementary school, however its use is reduced in the other cycles. Through this research work, we wanted to start to study how the game could be an effective and relevant learning substrate in our 1st year of primary school and 2nd year of primary school for the development of strategies in connection with the control of the numbers and the procedures of calculation. For that purpose, we created a new game to enlist ourpupils by appealing to the imagination of the pupils and allowing to reinvest knowledge and mathematical skills and to develop strategies.Le jeu est un outil pédagogique très répandu en cycle 1 à l’école élémentaire, cependant son utilisation est réduite dans les cycles supérieurs. Au travers de ce travail de recherche, nous avons voulu commencer à étudier en quoi le jeu pourrait être un support d’apprentissage efficace et pertinent dans nos classes de CP et de CE1 pour le développement de stratégies en lien avec la maitrise des nombres et des procédures de calcul. Pour cela, nous avons créé un nouveau jeu pour enrôler nos élèves faisant appel à l’imaginaire des élèves et permettant de réinvestir des connaissances et compétences mathématiques et de développer des stratégies

Agricultural impacts of large-scale variability of the West African monsoon

Agriculture in the Sudano-Sahelian zone is heavily dependent on the seasonal characteristics of rainfall. This study seeks to characterise components of regional climatic variability and their impact on simulated, attainable, plot level yields of millet. First we describe at a regional scale two main events in the seasonal pattern of the monsoon over West Africa by using a daily rainfall dataset over the 1968-1990 period, that is, (i) the onset of the summer monsoon characterised by an abrupt northward shift of the ITCZ from 5°N to 10°N around 24 June, and (ii) large and coherent intra-seasonal rainfall fluctuations at two different time scales, around 15 and 40 days. Second, we investigate the impact of these regional phenomena on local crop yields using SARRAH, a crop model simulating attainable yield, i.e. water and climate limited but not nutrient limited yield, by means of sensitivity analyses. The response of attainable yield to sowing date is studied for 19 years of the 1968-1990 period for a 90-day millet crop at Niamey. The results indicate that information on regional climate dynamics might help improve crop production locally. It is shown that the regional onset of the monsoon is very close to the ideal sowing date, derived from simulations, at Niamey and that simulated yields are much higher for these dates than for those identified with the traditional rule based on local rainfall. Taking into account the regional onset of monsoon thus seems to improve the relationship between water available and water used by the plant, and thus seems to potentially increase crop water use. Where attainable, simulated yields using the monsoon onset criterion are low, they are generally caused by intra-seasonal dry spells that have differential impact depending on phenological stage of the crop. (Résumé d'auteur

Ajournement de l'affaire de la ville de Rozoy, lors de la séance du 7 février 1790

Houdet Guillaume-Benoît, Cernon Jean-Baptiste de Pinteville, baron de. Ajournement de l'affaire de la ville de Rozoy, lors de la séance du 7 février 1790. In: Archives Parlementaires de 1787 à 1860 - Première série (1787-1799) Tome XI - Du 24 décembre 1789 au 1er mars 1790. Paris : Librairie Administrative P. Dupont, 1880. p. 488