Discovery of Highly Potent Dual Orexin Receptor Antagonists via a Scaffold‐Hopping Approach

Starting from suvorexant (trade name Belsomra), we successfully identified interesting templates leading to potent dual orexin receptor antagonists (DORAs) via a scaffold‐hopping approach. Structure–activity relationship optimization allowed us not only to improve the antagonistic potency on both orexin 1 and orexin 2 receptors (Ox1 and Ox2, respectively), but also to increase metabolic stability in human liver microsomes (HLM), decrease time‐dependent inhibition of cytochrome P450 (CYP) 3A4, and decrease P‐glycoprotein (Pgp)‐mediated efflux. Compound 80 c [{(1S,6R)‐3‐(6,7‐difluoroquinoxalin‐2‐yl)‐3,8‐diazabicyclo[4.2.0]octan‐8‐yl}(4‐methyl‐[1,1′‐biphenyl]‐2‐yl)methanone] is a potent and selective DORA that inhibits the stimulating effects of orexin peptides OXA and OXB at both Ox1 and Ox2. In calcium‐release assays, 80 c was found to exhibit an insurmountable antagonistic profile at both Ox1 and Ox2, while displaying a sleep‐promoting effect in rat and dog models, similar to that of the benchmark compound suvorexant.     

Design of New Cardanol Derivative: Synthesis and Application as Potential Biobased Plasticizer for Poly(lactide)

A novel biobased plasticizer made of cardanol is designed for poly(lactide) (PLA). This cardanol‐derived plasticizer, i.e., methoxylated hydroxyethyl cardanol (MeCard), is synthesized through methoxylation of the double bonds on the side chain of cardanol, and characterized by ¹H NMR and mass spectrometry. The plasticization effect of MeCard on the molecular structure, morphology, thermal and mechanical properties of PLA is evaluated and compared to that of a commercial cardanol, i.e., hydroxyethyl cardanol (pCard). The plasticization efficiency of MeCard is demonstrated by a substantial decrease of the glass transition temperature and storage modulus together with a significant increase of the elongation at break as compared to neat PLA. Moreover, MeCard exhibits higher plasticization performance than pCard toward PLA. Such behavior is related to a higher miscibility and compatibility between PLA and MeCard thanks to the methoxylation of the double bonds on the side chain of cardanol as shown by SEM micrographs.

     

Synthesis and Microstructural Characterization of Substoichiometric Ti2Al(CxNy) Solid Solutions and Related Ti2AlCx and Ti2AlN End‐Members

Ti, TiC, Al and AlN powders were mixed to synthesize Ti₂Al(C_xN_y) (x + y < 1) solid solutions, Ti₂AlC_x (x < 1) and Ti₂AlN‐related end‐members by hot isostatic pressing at 1400°C/80 MPa for 4 h. For the pure carbides, it is demonstrated that single‐phased samples can only be obtained when about 15% of substoichiometry on the carbon site is applied. Such a result likely implies that Ti₂AlC_x can only exist in a narrow range of carbon composition. Ti₂AlN nitride can be synthesized with y = 1. Assuming that vacancy content varies linearly from 0 to 0.15 going from Ti₂AlN to Ti₂AlC_0.85 in the solid solutions, element concentrations have been calculated to synthesize different solid solutions. Thus, it is demonstrated that single‐phased and fully dense Ti₂Al(C_0.23N_0.71), Ti₂Al(C_0.45N_0.45), and Ti₂Al(C_0.66N_0.22) carbonitrides can be synthesized.     

Analysis of the Shrinkage Effect on Mass Transfer During Convective Drying of Sawdust/Sludge Mixtures

Convective drying of wastewater sludges and sawdust/sludge mixtures was studied. The first part of this work was an experimental study performed in a cross-flow convective dryer using 500 g of wet material extruded through a disk with circular dies of 12 mm. The results showed that the sawdust addition has a positive impact on the drying process from a mass ratio of 2/8, on a dry basis, with observed drying rates higher than the original sludge. The second part of this work consisted of developing a drying model in order to identify the internal diffusion coefficient and convective mass transfer coefficient from the experimental data. A comparison was made between fitted drying curves, well represented by the Newton's model, and the analytical solutions of the diffusion equation applied to a finite cylinder. Variations of dimensional characteristics, such as the volume and exchange surface of the sample bed, were obtained by X-ray tomography. This technique allowed us to confirm that shrinkage, which is an important phenomenon occurring during sludge and sawdust/sludge mixture drying, must be taken into account. The results showed that both the internal diffusion coefficient and convective mass transfer coefficient were affected by mixing and sawdust addition. The internal diffusion coefficient changed from 7.77 × 10^?9 m²/s for the original sludge to 7.01 × 10^?9 m²/s for the mixed sludge and then increased to 8.35 × 10^?9 m²/s for the mixture of a mass ratio of 4/6. The convective mass transfer coefficient changed from 9.70 × 10^?8 m/s for the original sludge to 8.67 × 10^?8 m/s for the mixed sludge and then increased to 12.09 × 10^?8 m/s for the mixture of a mass ratio of 4/6. These results confirmed that sawdust addition was beneficial to the sludge drying process as the mass transfer efficiency between the air and material increased. Reinforcing the texture of sludge by adding sawdust can increase the drying rate and decrease the drying time, and then the heat energy supply will be reduced significantly. The study also showed that neglecting shrinkage phenomenon resulted in an overestimation for the internal diffusion coefficient for the convective drying of sludges and sawdust/sludge mixtures.     

An axiomatic characterization of the ranking based on the h-index and some other bibliometric rankings of authors

In the last few years, many new bibliometric rankings or indices have been proposed for comparing the output of scientific researchers. We propose a formal framework in which rankings can be axiomatically characterized. We then present a characterization of some popular rankings. We argue that such analyses can help the user of a ranking to choose one that is adequate in the context where she/he is working.     

Image segmentation by a contrario simulation

Segmenting an image into homogeneous regions generally involves a decision criterion to establish whether two adjacent regions are similar. Decisions should be adaptive to get robust and accurate segmentation algorithms, avoid hazardous a priori and have a clear interpretation. We propose a decision process based on a contrario reasoning: two regions are meaningfully different if the probability of observing such a difference in pure noise is very low. Since the existing analytical methods are intractable in our case, we extend them to allow a mixed use of analytical computations and Monte-Carlo simulations. The resulting decision criterion is tested experimentally through a simple merging algorithm, which can be used as a post-filtering and validation step for existing segmentation methods.     

Effect of initial powder type on the hydrogen storage properties of high-pressure torsion consolidated Mg

While severe plastic deformation (SPD) on bulk samples has been widely applied for modifying the H-sorption properties, there has been little attention towards the use of SPD on powder materials. In this context, the aim of the present work was to compare the H-storage properties of high-pressure torsion (HPT) consolidated products obtained from two distinct Mg powder precursors: atomized micro-sized and condensed ultrafine powder particles. The results showed that the nature of the initial powder precursor had a pronounced effect on the H-sorption behavior. The HPT product obtained from the condensed ultrafine powder showed faster absorption kinetics than the consolidated product obtained from the atomized powder. However, the HPT product obtained from atomized powder could absorb more hydrogen and showed faster desorption kinetics corresponding to a lower activation energy. These results are discussed by taking into account the effectiveness of the HPT process to refine the grain sizes and differences in the dispersion of fine MgO oxide particles.     

Experimental and Molecular Dynamics Simulations of Tribochemical Reactions with ZDDP: Zinc Phosphate–Iron Oxide Reaction

Zinc phosphate glass is considered to be the main constituent of tribofilms generated under boundary lubrication with zinc dialkyldithiophosphate (ZDDP), a well-known antiwear additive. The reaction occurring during friction between zinc phosphate glasses and steel native iron oxide layer is investigated by both an experimental approach and by Molecular Dynamics simulations (MD). The importance of this “tribochemical” reaction in the general ZDDP antiwear process is discussed.     

光学仿真分析在光电传感器开发过程中的应用

1 引言 光电传感器是指利用光电效应作为传感原理的传感器件,它主要由光源、光学通路、光电探测器等部分.光源发出的光照射到待检测的目标物体上,被目标物体调制后被光电探测器所接收.     

A simple analytical model to study and control azimuthal instabilities in annular combustion chambers

This study describes a simple analytical method to compute the azimuthal modes appearing in annular combustion chambers and help analyzing experimental, acoustic and large eddy simulation (LES) data obtained in these combustion chambers. It is based on a one-dimensional zero Mach number formulation where N burners are connected to a single annular chamber. A manipulation of the corresponding acoustic equations in this configuration leads to a simple dispersion relation which can be solved by hand when the interaction indices of the flame transfer function are small and numerically when they are not. This simple tool is applied to multiple cases: (1) a single burner connected to an annular chamber (N = 1), (2) two burners connected to the chamber (N = 2), and (3) four burners (N = 4). In this case, the tool also allows to study passive control methods where two different types of burners are mixed to control the azimuthal mode. Finally, a complete helicopter chamber (N = 15) is studied. For all cases, the analytical results are compared to the predictions of a full three-dimensional Helmholtz solver and a very good agreement is found. These results show that building very simple analytical tools to study azimuthal modes in annular chambers is an interesting path to control them.