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1.
Dense pressure-sintered reaction-bonded Si3N4 (PSRBSN) ceramics were obtained by a hot-press sintering method. Precursor Si powders were prepared with Eu2O3–MgO–Y2O3 sintering additive. The addition of Eu2O3–MgO–Y2O3 was shown to promote full nitridation of the Si powder. The nitrided Si3N4 particles had an equiaxial morphology, without whisker formation, after the Si powders doped with Eu2O3–MgO–Y2O3 were nitrided at 1400 °C for 2 h. After hot pressing, the relative density, Vickers hardness, flexural strength, and fracture toughness of the PSRBSN ceramics, with 5 wt% Eu2O3 doping, were 98.3 ± 0.2%, 17.8 ± 0.8 GPa, 697.0 ± 67.0 MPa, and 7.3 ± 0.3 MPa m1/2, respectively. The thermal conductivity was 73.6 ± 0.2 W m?1 K?1, significantly higher than the counterpart without Eu2O3 doping, or with ZrO2 doping by conventional methods.  相似文献   
2.
孙搏  付淑军  陈桂良  李丽 《金属学报》2021,26(10):1095-1102
药物相互作用改变了剂量效应关系,可能会降低疗效或增加毒性,是临床应用中合并用药治疗时重要的考虑因素。预测具有临床意义的药物相互作用是药物研发过程中获益风险评估的重要环节。本文概述了药物研发过程中药物相互作用研究的目的和意义,体内和体外研究的主要内容;梳理分析了2020年国家药品监督管理局(National Medical Products Administration, NMPA)和美国食品药品监督管理局(Food and Drug Administration, FDA)批准上市的新药药物相互作用研究情况,旨在为我国药物研发过程中药物相互作用研究及其监管审评提供参考。  相似文献   
3.
Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points.  相似文献   
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5.
In this article, the results of the NaWuReT (Early Career Reaction Engineers) workshop on the topic “Are we doing relevant science?” are presented. The topics “(In)surmountable hurdles for Citizen Scientists in reaction engineering?” and “Circular Economy in reaction engineering with/for society?” were discussed. Therefrom, a variety of ideas and suggestions were extracted.  相似文献   
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Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.  相似文献   
8.
In the present investigation, we examined whether a change in whole body energy fluxes could affect ovarian follicular development, employing mice ectopically expressing uncoupling protein 1 in skeletal muscle (UCP1-TG). Female UCP1-TG and wild-type (WT) mice were dissected at the age of 12 weeks. Energy intake and expenditure, activity, body weight and length, and body composition were measured. Plasma insulin, glucose, leptin, plasma fibroblast growth factor 21 (FGF21) and plasma insulin-like growth factor 1 (IGF1) levels were analyzed and ovarian follicle and corpus luteum numbers were counted. IGF1 signaling was analyzed by immunohistochemical staining for the activation of insulin receptor substrate 1/2 (IRS1/2) and AKT. UCP1-TG female mice had increased energy expenditure, reduced body size, maintained adiposity, and decreased IGF1 concentrations compared to their WT littermates, while preantral and antral follicle numbers were reduced by 40% and 60%, respectively. Corpora lutea were absent in 40% of the ovaries of UCP1-TG mice. Phospho-IRS1, phospho-AKT -Ser473 and -Thr308 immunostaining was present in the granulosa cells of antral follicles in WT ovaries, but faint to absent in the antral follicles of UCP1-TG mice. In conclusion, the reduction in circulating IGF1 levels due to the ectopic expression of UCP1 is associated with reduced immunostaining of the IRS1-PI3/AKT pathway, which may negatively affect ovarian follicle development and ovulation.  相似文献   
9.
本文以肇庆市固体废物产业发展为实例,阐明全市固体废物产业发展现状以及发展方向,并提出了相应的策略。  相似文献   
10.
This paper asks how the livability of socially disadvantaged urban neighborhoods can be improved with the help of publicly funded area-based urban regeneration. It builds on the history of area-based regeneration policies in Germany aiming at upgrading and resolving urban problems at the neighborhood level. Its main argument is as follows. First, the fate of conventional physical upgrading policies focusing on the livability of deprived urban areas depends on the development environment. While successful upgrading sometimes makes inner-city neighborhoods so attractive that they run into a trend towards gentrification and displacement of the urban poor, the stabilization of less privileged areas cannot always be guaranteed. Second, alternative approaches are needed, linking limited physical upgrading with socially oriented policies, building on strategies like neighborhood management and empowerment. Third, they can make a substantial contribution to stabilizing deprived neighborhoods, thereby improving the general living conditions and the opportunities of the urban poor. However, they require at least some permanent intervention. Thus, they transcend the logic of area-based regeneration normally limited to restoring faith into the private real estate market and thereby directing inward investment into them that improves the quality of the physical environment. Fourth, they are hardly able to overcome significant negative stigmatization in cities that are severely hit by economic downturn and population decline. This is especially true when they act as arrival areas for consecutive waves of migrants, making it necessary to redefine the role of those areas in cities and accepting their high concentration of urban problems as a starting point for different area-based policies dealing with them. The key empirical background of the paper is the German system of urban development grants and an evaluation of the so-called program of “socially integrative city”.  相似文献   
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