Cu(I)-Catalyzed Alkynylation of Quinolones

[Image: see text] Herein we report the first alkynylation of quinolones with terminal alkynes under mild reaction conditions. The reaction is catalyzed by Cu(I) salts in the presence of a Lewis acid, which is essential for the reactivity of the system. The enantioselective version of this transformation has also been explored, and the methodology has been applied in the synthesis of the enantioenriched tetrahydroquinoline alkaloid cuspareine

Modelling natural transition on hydrofoils for application in underwater gliders

The paper explores the use of the Local Correlation Transition (LCTM) RANS model capable of predicting transition to turbulence in application to underwater glider performance prediction. Validation of the method is established by analysing the flow past SD7003 and SD8020 hydrofoil sections and comparing with experimental data. Finally, flow past a swept wing suitable for use on an underwater glider is predicted. The results indicate significant improvement in capturing the flow physics in comparison to a standard shear stress transport (SST) k-omega model. Three-dimensional effects are found to play a significant role in the flow behaviour due to the significant sweep of the foil considered

Exploiting synergistic effects in organozinc chemistry for direct stereoselective C‐glycosylation reactions at room temperature

Pairing a range of bis(aryl) zinc reagents ZnAr2 with the stronger Lewis acidic [(ZnArF2)] (ArF = C6F5), enables highly stereoselective cross‐coupling between glycosyl bromides and ZnAr2 without the use of a transition metal. Reactions occur at room temperature with excellent levels of stereoselectivity, where ZnArF2 acts as a non‐coupling partner although its presence is crucial for the execution of the C(sp2)‐C(sp3) bond formation process. Mechanistic studies have uncovered a unique synergistic partnership between the two zinc reagents, which circumvents the need for transition‐metal catalysis or forcing reaction conditions. Key to the success of the coupling is the avoidance of solvents that act as Lewis bases vs. diarylzinc compounds (e.g. THF

Regards comparatistes sur la réforme de la responsabilité civile: le rapprochement des responsabilités contractuelle et délictuelle dans l’avant-projet de réforme, abordé sous l’angle du droit compare

This article is a comparative study of the Dutch and French legal systems regarding four major points of the French governmental reform project for civil liability : concurrence of actions; limitation and exemption clauses; causation; the obligation to mitigate your own damage. It also addresses the following issues: the question of damages to the environment, and the role of transitional provisions. Through these different areas of study, this article shows that the traditional distinction between contractual and tortuous liability is not necessarily relevant and may even prove a nuisance in certain cases. The contribution is followed by a reaction of Mme. De Cabarrus, magistrate at the French Ministry of Justice

Assessment of Translocator Protein Density, as Marker of Neuroinflammation, in Major Depressive Disorder: A Pilot, Multicenter, Comparative, Controlled, Brain PET Study (INFLADEP Study)

Background: Major depressive disorder (MDD) is a serious public health problem with high lifetime prevalence (4.4–20%) in the general population. The monoamine hypothesis is the most widespread etiological theory of MDD. Also, recent scientific data has emphasized the importance of immuno-inflammatory pathways in the pathophysiology of MDD. The lack of data on the magnitude of brain neuroinflammation in MDD is the main limitation of this inflammatory hypothesis. Our team has previously demonstrated the relevance of [18F] DPA-714 as a neuroinflammation biomarker in humans. We formulated the following hypotheses for the current study: (i) Neuroinflammation in MDD can be measured by [18F] DPA-714; (ii) its levels are associated with clinical severity; (iii) it is accompanied by anatomical and functional alterations within the frontal-subcortical circuits; (iv) it is a marker of treatment resistance.Methods: Depressed patients will be recruited throughout 4 centers (Bordeaux, Montpellier, Tours, and Toulouse) of the French network from 13 expert centers for resistant depression. The patient population will be divided into 3 groups: (i) experimental group—patients with current MDD (n = 20), (ii) remitted depressed group—patients in remission but still being treated (n = 20); and, (iii) control group without any history of MDD (n = 20). The primary objective will be to compare PET data (i.e., distribution pattern of neuroinflammation) between the currently depressed group and the control group. Secondary objectives will be to: (i) compare neuroinflammation across groups (currently depressed group vs. remitted depressed group vs. control group); (ii) correlate neuroinflammation with clinical severity across groups; (iii) correlate neuroinflammation with MRI parameters for structural and functional integrity across groups; (iv) correlate neuroinflammation and peripheral markers of inflammation across groups.Discussion: This study will assess the effects of antidepressants on neuroinflammation as well as its role in the treatment response. It will contribute to clarify the putative relationships between neuroinflammation quantified by brain neuroimaging techniques and peripheral markers of inflammation. Lastly, it is expected to open innovative and promising therapeutic perspectives based on anti-inflammatory strategies for the management of treatment-resistant forms of MDD commonly seen in clinical practice.Clinical trial registration (reference: NCT03314155): https://www.clinicaltrials.gov/ct2/show/NCT03314155?term=neuroinflammation&cond=depression&cntry=FR&rank=

An efficient and accurate overset grid technique applied to maritime CFD

Ship manoeuvring and other maritime applications pose complex challenges involving the motion of multiple bodies. The overset method enables simulations of such cases using computational fluid dynamics (CFD) by allowing arbitrary movement of any number of meshes. However, this versatility comes at a cost in terms of performance and accuracy. This research, therefore, aims to provide a modern, efficient and accurate overset method and study its reliability using advanced Verification techniques. To this end, a novel overset method that includes a wide variety of interpolation schemes has been implemented and is the basis for quantitative and qualitative error analysis studies performed on several test cases, as well as an investigation on computational performance.Quantifying local and global errors, convergence orders, and mass imbalance for different interpolation schemes on several test cases allows to draw guidelines for both overset method users and developers. Moreover, the range of test cases used, such as a realistic 3D unsteady RANS manufactured solution of a recirculation bubble or a rudder-propeller flow, allows to extend the conclusions to many maritime applications. The results show that the choice of interpolation scheme has a significant impact on accuracy. First order schemes lower the overall convergence order of the discretisation error, increasing the amount of artefacts visible in the field and resulting in larger high-frequency temporal oscillations. Higher order schemes such as second and third order accurate ones help to limit the error production and maintain second order accuracy of the solver's discretisation scheme. However, the limitations of first order schemes do not come with a significant reduction in computational overhead. In fact, the second order nearest cell gradient is even cheaper than the first order inverse distance scheme. Finally, the third order least squares scheme, though more expensive, is still a viable option as it shows only a 8% performance overhead after several sequential and parallel programming performance tuning operations. In addition to providing guidelines and analysis methodologies, this work has also produced two opensource tools aimed at helping Verification, with the automatic generation of manufactured solutions and the computation of statistical uncertainties

On the need for higher order interpolation with overset grid methods

Overset methods, by overlapping several grids, allow large and arbitrary motion of bodies. First developed for the aerospace industry (Benek et al., 1985), it is now used for a wider range of applications like maritime ones (Carrica et al., 2013). At the fringes of each grid, the coupling is done by interpolating field variables. This interpolation step is key in any overset computations since the choice of the interpolation scheme directly influences the accuracy of the solution and the performance. Most overset implementations done for unstructured CFD codes uses 1st or at most 2nd order interpolation schemes (Gatin et al., 2018, V ̈olkner et al., 2017, Chandar et al., 2018) but higher order interpolation schemes (3rd or 4th) are not often studied (Chandar, 2019). This paper evaluates the use of higher order (higher than 2nd order) interpolation schemes for the overset method by comparing the accuracy of different interpolation schemes on a Poiseuille flow test case, no performance study is however conducted here. The overset implementation used in this study is a coupling between the CFD solver ReFRESCO and the overset library Suggar++ (Noack and Boger, 2009)

HOSPITALISATION DE JOUR ANNUELLE EN DIABETOLOGIE (INTERET DANS LA PRISE EN CHARGE DES DIABETIQUES A PROPOS D'UN ECHANTILLON DE 150 PATIENTS SUIVIS DANS UN HOPITAL GENERAL)

REIMS-BU Santé (514542104) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF