Effects of radiative heat transfer on the structure of turbulent supersonic channel flow

International audienceThe interaction between turbulence in a minimal supersonic channel and radiative heat transfer is studied using large-eddy simulation. The working fluid is pure water vapour with temperature-dependent specific heats and molecular transport coefficients. Its line spectra properties are represented with a statistical narrow-band correlated-k model. A grey gas model is also tested. The parallel no-slip channel walls are treated as black surfaces concerning thermal radiation and are kept at a constant temperature of 1000 K. Simulations have been performed for different optical thicknesses (based on the Planck mean absorption coefficient) and different Mach numbers. Results for the mean flow variables, Reynolds stresses and certain terms of their transport equations indicate that thermal radiation effects counteract compressibility (Mach number) effects. An analysis of the total energy balance reveals the importance of radiative heat transfer, compared to the turbulent and mean molecular heat transport

Application of particle filters to regional-scale wildfire spread

European Conference on Thermophysical Properties (ECTP)European Conference on Thermophysical Properties (ECTP), Porto, PORTUGALPorto, PORTUGAL, SEP 05-05, 2014SEP 05-05, 2014International audienceThis paper demonstrates the capability of particle filters for sequentially improving the simulation and forecast of wildfire propagation as new fire front observations become available. Particle filters, also called Sequential Monte Carlo (SMC) methods, fit into the domain of inverse modeling procedures, where measurements are incorporated (assimilated) into a computational model so as to formulate some feedback information on the uncertain model state variables and/or parameters, through representations of their probability density functions (PDF). Based on a simple sampling importance distribution and resampling techniques, particle filters combine Monte Carlo samplings with sequential Bayesian filtering problems. This study compares the performance of the Sampling Importance Resampling (SIR) and of the Auxiliary Sampling Importance Resampling (ASIR) filters for the sequential estimation of a progress variable and of vegetation parameters of the Rate Of fire Spread (ROS) model, which are all treated as state variables. They are applied to a real-world case corresponding to a reduced-scale controlled grassland fire experiment for validation; results indicate that both the SIR and the ASIR filters are able to accurately track the observed fire fronts, with a moderate computational cost. Particle filters show, therefore, their good ability to predict the propagation of controlled fires and to significantly increase fire simulation accuracy. While still at an early stage of development, this data-driven strategy is quite promising for regional-scale wildfire spread forecasting

Evaluating the Efficacies of Carbapenem/β-Lactamase Inhibitors Against Carbapenem-Resistant Gram-Negative Bacteria in vitro and in vivo

BackgroundCarbapenem-resistant Gram-negative bacteria are a major clinical concern as they cause virtually untreatable infections since carbapenems are among the last-resort antimicrobial agents. β-Lactamases implicated in carbapenem resistance include KPC, NDM, and OXA-type carbapenemases. Antimicrobial combination therapy is the current treatment approach against carbapenem resistance in order to limit the excessive use of colistin; however, its advantages over monotherapy remain debatable. An alternative treatment strategy would be the use of carbapenem/β-lactamase inhibitor (βLI) combinations. In this study, we assessed the in vitro and in vivo phenotypic and molecular efficacies of three βLIs when combined with different carbapenems against carbapenem-resistant Gram-negative clinical isolates. The chosen βLIs were (1) Avibactam, against OXA-type carbapenemases, (2) calcium-EDTA, against NDM-1, and (3) Relebactam, against KPC-2.MethodsSix Acinetobacter baumannii clinical isolates were screened for blaOXA-23-like, blaOXA-24/40, blaOXA-51-like, blaOXA-58, and blaOXA-143-like, and eight Enterobacteriaceae clinical isolates were screened for blaOXA-48, blaNDM-1, and blaKPC-2. The minimal inhibitory concentrations of Imipenem (IPM), Ertapenem (ETP), and Meropenem (MEM) with corresponding βLIs for each isolate were determined. The efficacy of the most suitable in vitro treatment option against each of blaOXA-48, blaNDM-1, and blaKPC-2 was assessed via survival studies in a BALB/c murine infection model. Finally, RT-qPCR was performed to assess the molecular response of the genes of resistance to the carbapenem/βLI combinations used under both in vitro and in vivo settings.ResultsCombining MEM, IPM, and ETP with the corresponding βLIs restored the isolates’ susceptibilities to those antimicrobial agents in 66.7%, 57.1%, and 30.8% of the samples, respectively. Survival studies in mice revealed 100% survival rates when MEM was combined with either Avibactam or Relebactam against blaOXA-48 and blaKPC-2, respectively. RT-qPCR demonstrated the consistent overexpression of blaOXA-48 upon treatment, without hindering Avibactam’s activity, while blaNDM-1 and blaKPC-2 experienced variable expression levels upon treatment under in vitro and in vivo settings despite their effective phenotypic results.ConclusionNew carbapenem/βLI combinations may be viable alternatives to antimicrobial combination therapy as they displayed high efficacy in vitro and in vivo. Meropenem/Avibactam and Meropenem/Relebactam should be tested on larger sample sizes with different carbapenemases before progressing further in its preclinical development

Synthesis, crystal structure, DFT calculations, Hirshfeld surface analysis, energy frameworks, molecular dynamics and docking studies of novel isoxazolequinoxaline derivative (IZQ) as anti-cancer drug

Quinoxaline derivatives with the molecular formula C8H6N2] also named benzopyrazines, which are a valuable class of heterocyclic compounds useful for their numerous industrial and pharmaceutical applications. The new isoxazolquinoxalin (IZQ) 3-pheny1-14(3-(p-toly1)-4,5-dihydroisoxazol-5yl)methyl)quinoxalin-2(1H)- one (5) has been synthesized with good yield by stirring the compounds of 1-allyl-3-phenylquinoxalin-2(1H)-one (3, 3.8mmol), and (E)-4 methylbenzaldehydeoxime (4, 1.3mmol) in 20 ml of chloroform. The aqueous solution of sodium hypochlorite (10 ml of water bleach 12 degrees) was added drop wise using bromine funnel. The mixture was stirring at 0 degrees C temperature for 6 hours. Then it dried to obtain a crude product which on recrystallization with ethanol afforded the title compound (5) as colourless rectangular block shape crystals, and then confirmed by H NMR, LC-MS spectra. The structure of the compound has been confirmed by single crystal X-ray diffraction technique. The compound crystallizes in the monoclinic crystal system with the space group P2(1)/c. The unit cell constants; a =15.9437(6) angstrom, b =16.3936(6) angstrom, c =7.4913(3) angstrom, and beta =94.178(2)degrees. DFT calculations were carried out and HOMO-LUMO energy levels have been determined. In the structure, both Intermolecular and intramolecular hydrogen bonds of the type C-H center dot center dot center dot O were observed along with C-H center dot center dot center dot cg interactions. Hirshfeld surface studies were performed to understand the different interaction contacts of the molecule and the molecular packing strength of the crystal. Energy frameworks were constructed through different intermolecular interaction energies to investigate the stability of the compound and to know type of the dominate energy. Docking studies predicted anti-cancer activity of the title molecule against homo sapiens protein (pdb code:6HVH) and exhibited prominent interactions at active site region. (C) 2021 Elsevier B.V. All rights reserved

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Nanoarchitectonics and Molecular Docking of 4-(Dimethylamino)Pyridin-1-Ium 2-3 Methyl-4-Oxo-Pyri-Do[1,2-<i>a</i>]Pyrimidine-3-Carboxylate

A retro-Claisen reaction of 1-(4-oxo-4H-pyrido [1,2-a]pyrimidin-3-yl)butane-1,3-dione, 3, in the presence of potassium hydroxide and 4-dimethylamino-pyridine has been carried out, leading to 4-(dimethylamino)pyridin-1-ium 2-methyl-4-oxo-pyrido [1,2-a]pyrimidine-3-carboxylate 5. A plausible mechanism explaining the formation of the title compound has been proposed. A single-crystal X-ray diffraction analysis confirms the crystal structure of the isolated organic salt (5). In the crystal, the title compound adopts a layered structure where there are stacks of cations and anions formed by slipped π-stacking interactions. These stacks are linked by regions consisting of water molecules that are hydrogen-bonded together. DFT and Hirshfeld surface analysis supported the experimental results of the molecular geometry and the intercontacts between different units in the crystal. The druglikeness, ADMET properties, and predicted targets were investigated, and the observed results suggest that 5 may act as a carbonic anhydrase I inhibitor. The assumption is confirmed by docking 5 into the active binding site of carbonic anhydrase, which shows it to have good binding affinities and to form stable complexes with the active residues of carbonic anhydrase I

Approximation de schiff appliquée au calcul de propriétés radiatives de micro-organismes photosynthétiques et résolution par la méthode de monte carlo

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