Peroxisome Proliferator-Activated Receptors in HCV-Related Infection

The topic of peroxisome proliferator-activated receptors has been developed in the field of hepatology allowing envisaging therapeutic strategies for the most frequent chronic liver diseases such as chronic infection with hepatitis C virus (HCV). PPARs contribute to wide physiological processes within the liver such as lipid/glucid metabolisms, inflammatory response, cell differentiation, and cell cycle. In vitro experiments and animal studies showed that PPARα discloses anti-inflammatory property, and PPARγ discloses anti-inflammatory, antifibrogenic, and antiproliferative properties in the liver. Experimental and human studies showed impaired PPARs expression and function during HCV infection. The available nonhepatotoxic agonists of PPARs may constitute a progress in the therapeutic management of patients chronically infected with HCV

New insights in formaldehyde-induced detoxification of the tetanus toxin: Chemical modification stoichiometry and characterization of intra- and inter-molecular cross-links

The active ingredient of the tetanus vaccine, known as tetanus toxoid (TTD, 150 kDa), is prepared by inactivation of the tetanus toxin with formaldehyde. This chemical treatment determines the efficiency and innocuity of the vaccine. The detoxification chemistry has been qualitatively studied regarding the nature and positioning of some formaldehyde-induced modifications. However, neither the stoichiometry of the chemical modifications or intra- and inter-chain cross-linking have been yet characterized, despite being of great interest for the definitive elucidation of the detoxification mechanism as well as for future manufacturing follow-up. The aim of the present study is to assess the impact of formaldehyde on TTD by identifying, mapping, and quantifying as exhaustively as possible, all formaldehyde-induced modifications over the entire three-dimensional (3D) structure of the protein. Please click Download on the upper right corner to see the full abstract

Direct numerical simulation of the impact of a droplet onto a hot surface above the Leidenfrost temperature

In this paper, we compare numerical simulations and experiments on droplets impinging onto a hot surface at a temperature well above the Leidenfrost point, for different impacting Weber numbers ranging from 7 to 45. We use a novel numerical method for the simulation of two-phase flows with phase change (evaporation and boiling) which accounts for the heterogeneous thermodynamic conditions at the liquid/gas interface. We present the results of experimental and numerical values for the droplet shape, its spreading diameter and its loss of momentum. The numerical simulations determine the time-evolution of the average vapor layer thickness, which is typically from one to two orders of magnitude smaller than the initial droplet diameter. Thermal transfer between the liquid and the gas phases are also investigated both numerically and experimentally. In the numerical results, like in the experiments, the droplet heating increases with the impacting Weber numbers. The fully resolved direct numerical simulations allow for the accurate description of the multi-scale complex problem involving both fluid mechanics and coupled heat and mass transfer

Chapitre 5. L’époque moderne

Entre la fin de l’activité agricole, phase 4B/C datable du milieu du Ve siècle apr. J.-C., et la reprise d’une installation au début de l’époque moderne, aucune trace d’occupation ni même de fréquentation n’a été perçue sur le site, qui paraît totalement abandonné durant près d’un millénaire. La découverte d’un fragment de bol à la croix en céramique pisane caractéristique du XIVe siècle (Amouric et al. 1999, 30) ne peut à elle seule indiquer une reprise de l’activité sur le site durant le ba..

Chapitre 3. Les abords des thermes de Villeneuve durant la deuxième moitié du Ier siècle apr. J.‑C.

1. La phase 3, état A Les vestiges en rapport avec cette phase concernent essentiellement les zones 1 et 3. Comme durant la phase précédente, la bande centrale (zone 2) est un terrain sableux exhaussé, dont les niveaux d’occupation ont totalement disparu. Il en est de même pour une partie de la zone 3, excavée lors des phases suivantes, mais la présence de structures situées sous les sols permet de retrouver la trace de quelques aménagements (fig. 58). 1.1. La zone 1 (P. E.) 1.1.1. Descripti..

Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program

The Tax oncoprotein encoded by the Human T-cell leukemia virus type 1 (HTLV-1) plays a pivotal role in viral persistence and pathogenesis. HTLV-1 infected cells proliferate faster than normal lymphocytes, expand through mitotic division and accumulate genomic lesions. Here, we show that Tax associates with the minichromosome maintenance MCM2-7 helicase complex and localizes to origins of replication. Tax modulates the spatiotemporal program of origin activation and fires supplementary origins at the onset of S phase. Thereby, Tax increases the DNA replication rate, accelerates S phase progression but also generates a replicative stress characterized by the presence of genomic lesions. Mechanistically, Tax favors p300 recruitment and histone hyperacetylation at late replication domains advancing their replication timing in early S phase

Ville et campagne de Fréjus romaine

En 2006, une fouille d’archéologie préventive, désignée sous le nom de « Villa Romana », a été réalisée dans le quartier de Villeneuve à Fréjus. Durant l’Antiquité il s’agit d’une zone périurbaine située entre la ville de Forum Iulii et le débouché de l’Argens. Connu depuis longtemps en raison de la présence d’un édifice thermal toujours en élévation, le quartier a été fouillé à plusieurs occasions et est interprété comme étant l’emplacement du camp de la flotte, établi après la bataille d’Actium. Celui-ci se transforme progressivement durant le Ier siècle apr. J.-C. en quartier suburbain au fur et à mesure que se développe Forum Iulii. Le secteur fouillé se situe dans la partie sud du camp, bordée par la mer durant les premiers temps de l’Antiquité. La fouille a permis de révéler la présence d’une plage aménagée. Les terrains ont ensuite été rapidement gagnés sur la mer, en raison d’une avancée rapide du littoral, que des études récentes ont permis de bien connaitre à Fréjus. Des jardins y sont alors aménagés. A partir du IIe siècle, cet espace est transformé en zone agricole, et constitue l’illustration de l’exploitation de la campagne aux portes de Fréjus, et cela, jusqu’à la fin de l’Antiquité. S’ensuit une longue période d’abandon de plusieurs siècles, avant que l’espace ne soit à nouveau voué à l’agriculture et ce jusqu’à l’orée des années soixante. Depuis, le développement de la ville actuelle de Fréjus a de nouveau transformé ce quartier en zone urbaine. Cet ouvrage, publié quelques années seulement après la fouille, présente l’ensemble des études archéologiques et paléoenvironnementales, réalisées à l’occasion de cette opération, largement pluridisciplinaire. Elles fournissent un contexte environnemental nouveau pour ce quartier antique et permettent de redéfinir un paysage à partir d’analyses bioarchéologiques et paléoécologiques récentes. L’étude de l’ensemble des mobiliers archéologiques est également présentée, en suivant la chronologie et l’évolution de ce quartier à travers l’Antiquité et l’époque moderne

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/)