Correlation between homogeneous propane pyrolysis and pyrocarbon deposition

International audiencePyrocarbon deposition through propane pyrolysis is studied in a 1-D hot-wall CVD furnace. The gas-phase pyrolysis is modelled with a partially reduced kinetic mechanism leading to polycyclic aromatic compounds (PAHs). The C2-C4 and C3 reaction paths are in competition for benzene formation. There is also an independent C3-C5 path leading to naphthalene. The gas-phase concentrations are correlated with experimental data including in-situ FTIR spectra intensities, pyro- carbon deposition rates, and pyrocarbon nanotextures. Rough Laminar pyrocarbon deposition appears to be more related to PAHs than Smooth Laminar pyrocarbon

Kinetic modeling of gas-phase decomposition of propane : correlation with pyrocarbon deposition

International audienceA chemical kinetic model for gas-phase pyrolysis of propane has been set up, partially reduced, and validated against FTIR measurements in a tubular hot-wall reactor at P = 2 kPa, and T = 900 to 1400 K. It confirms the notion of "maturation" from propane to lighter hydrocarbons, the to aromatic compounds and PAHs. The gas-phase composition above the substrate has been correlated to pyrocarbon deposition rates and to the deposit nanostructure. It is confirmed that the growth of the rough laminar (RL) form would be related to heavier gaseous species than for the smooth laminar (SL) form

CVD and CVI of pyrocarbon from various precursors

International audienceThe control of pyrocarbon (pyC) chemical vapor infiltration (CVI) is a key issue in the processing of high-performance C/C composites with applications in aerospace parts and braking technology. For years, the precise investigation of deposition kinetics and pyC nanometerscale anisotropy has been rehearsed in chemical vapor deposition (CVD) and several variants of CVI with various pore sizes, and using mostly propane, propylene, and methane as source precursors. A literature survey and the analysis of recent experimental data have helped to understand better the role of gas-phase intermediate species in the various nanotextural transitions; a coherent modeling frame, which is suitable for propane, propylene, and methane—the latter having a neatly lower reactivity—has been set up and tested against experimental results from independent teams. The relation between nanotexture and processing conditions is then explained

The treatment response of chronically hepatitis C virus-infected patients depends on interferon concentration but not on interferon gene expression in peripheral blood mononuclear cells.

International audienceThe current treatment of chronic hepatitis C is based on pegylated alpha interferon (PEG-IFN-α) and ribavirin. The aim of this study was to identify biological and clinical variables related to IFN therapy that could predict patient outcome. The study enrolled 47 patients treated with PEG-IFN and ribavirin combined therapy. The interferon concentration was measured in serum by a bioassay. The expression of 93 interferon-regulated genes in peripheral blood mononuclear cells was quantified by real-time quantitative reverse transcription-PCR (RT-PCR) before and after 1 month of treatment. The interferon concentration in the serum was significantly lower in nonresponders than in sustained virological responders. Moreover, a significant correlation was identified between interferon concentration and interferon exposition as well as body weight. The analysis of interferon-inducible genes in peripheral blood mononuclear cells among the genes tested did not permit the prediction of treatment outcome. In conclusion, the better option seems to be to treat patients with weight-adjusted PEG-IFN doses, particularly for patients with high weight who are treated with PEG-IFN-α2a. Although the peripheral blood mononuclear cell samples are the easiest to obtain, the measurement of interferon-inducible genes seems not be the best strategy to predict treatment outcome

LRP1 Receptor Controls Adipogenesis and Is Up-Regulated In Human and Mouse Obese Adipose Tissue

The cell surface low-density lipoprotein receptor-related protein 1, LRP1, plays a major role in lipid metabolism. The question that remains open concerns the function of LRP1 in adipogenesis. Here, we show that LRP1 is highly expressed in murine preadipocytes as well as in primary culture of human adipocytes. Moreover, LRP1 remains abundantly synthesised during mouse and human adipocyte differentiation. We demonstrate that LRP1 silencing in 3T3F442A murine preadipocytes significantly inhibits the expression of PPARγ, HSL and aP2 adipocyte differentiation markers after adipogenesis induction, and leads to lipid-depleted cells. We further show that the absence of lipids in LRP1-silenced preadipocytes is not caused by lipolysis induction. In addition, we provide the first evidences that LRP1 is significantly up-regulated in obese C57BI6/J mouse adipocytes and obese human adipose tissues. Interestingly, silencing of LRP1 in fully-differentiated adipocytes also reduces cellular lipid level and is associated with an increase of basal lipolysis. However, the ability of mature adipocytes to induce lipolysis is independent of LRP1 expression. Altogether, our findings highlight the dual role of LRP1 in the control of adipogenesis and lipid homeostasis, and suggest that LRP1 may be an important therapeutic target in obesity

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

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/)

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P &lt; 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men

Extension of the bifurcation method for diffusion coefficients to porous medium transport

International audienceWe present an extension of Bartlett's bifurcation method for the approximate computation of multicomponent diffusion coefficients in a gaseous mixture to diffusion in porous media. On behalf of the remark that the bifurcation coefficients Fi are merely proportional to the square root of the molar masses Mi, we state that Knudsen diffusion may also be represented through some bifurcation factor FK. This approximation is tested in a variety of cases, displaying good results except for very light gas species

Modélisation de l'infiltration chimique en phase vapeur isobare (I-CVI) : application au SiC et au pyrocarbone

Isobaric chemical vapor phase infiltration (I-CVI) is a process for developing thermostructural composites with ceramic matrix. The mastery of this type of process, especially in the case of densification by pyrocarbon, sometimes depends on heuristic knowledge. This work deals with the numerical modeling of the physical and chemical phenomena couples encountered in CVI and is therefore oriented around two major axes. A first aspect concerns the overall modeling of the process. This modelling includes the detailed study of aerothermochemical phenomena (diffusive and convective mass and heat transfers, homogeneous and heterogeneous chemical reactions) in a set comprising the reactor and the porous medium to be densified (preform). The aspects of multicomponent diffusion have been detailed in both media (Stefan-Maxwell laws and dusty gas model). This approach makes it possible to highlight the importance of the coupling between the porous medium and the reaction cavity, which is illustrated in the case of silicon carbide deposition. A second axis of study is that of the pyrolysis of propane in a CVD (Chemical Vapor Deposition) reactor. A detailed mechanism, leading to the formation of the first polycyclic aromatic hydrocarbons was studied, and compared to the experimental results obtained previously in the laboratory with relative good agreement. Sensitivity and principal component analyses were conducted to reduce the size of the chemical system and to highlight the pathways of formation of the main species present. A proposal for a reaction mechanism for pyrocarbon deposition, based on a Langmuir model, was also confronted with the experimental results. The approach undertaken should eventually allow a complete modelling of the development of carbon/carbon composites by isobaric CVI.L'infiltration chimique en phase vapeur isobare (I-CVI) est un procédé permettant d'élaborer des composites thermostructuraux à matrice céramique. La maitrise de ce genre de procédés, en particulier dans le cas de la densification par du pyrocarbone relève parfois de connaissances heuristiques. Le présent travail traite de la modélisation numérique des phénomènes physiques et chimiques couples rencontrés en CVI et s'oriente donc autour de deux axes majeurs. Un premier aspect concerne la modélisation globale du procédé. Cette modélisation inclut l'étude détaillée des phénomènes aérothermochimiques (transferts de masse et de chaleur diffusifs et convectifs, réactions chimiques homogènes et hétérogènes) dans un ensemble comprenant le réacteur et le milieu poreux à densifier (préforme). Les aspects de diffusion multicomposants ont été détaillés dans les deux milieux (lois de Stefan-Maxwell et modèle de gaz poussiéreux). Cette approche permet de mettre en évidence l'importance du couplage entre le milieu poreux et la cavité réactionnelle, ce qui est illustré dans le cas du dépôt de carbure de silicium. Un deuxième axe d'étude est celui de la pyrolyse du propane dans un réacteur de CVD (Chemical Vapor Deposition). Un mécanisme détaillé, conduisant à la formation des premiers hydrocarbures aromatiques polycycliques a été étudié, et comparé aux résultats expérimentaux obtenus antérieurement au laboratoire avec un relatif bon accord. Des analyses de sensibilité et des analyses en composantes principales ont été conduites afin de réduire la taille du système chimique et de mettre en évidence les voies de formation des principales espèces présentes. Une proposition de mécanisme réactionnel pour le dépôt de pyrocarbone, basé sur un modèle de Langmuir a également été confronté aux résultats expérimentaux. La démarche entreprise devrait à terme permettre une modélisation complète de l'élaboration de composites carbone/carbone par CVI isobare