药物相互作用研究在新药研发和审评决策中的应用

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。     

Densification mechanism and microstructure characteristics of nano- and micro- crystalline alumina by high-pressure and low temperature sintering

Fully dense ceramics with retarded grain growth can be attained effectively at relatively low temperatures using a high-pressure sintering method. However, there is a paucity of in-depth research on the densification mechanism, grain growth process, grain boundary characterization, and residual stress. Using a strong, reliable die made from a carbon-fiber-reinforced carbon (C_f/C) composite for spark plasma sintering, two kinds of commercially pure α-Al₂O₃ powders, with average particle sizes of 220 nm and 3 μm, were sintered at relatively low temperatures and under high pressures of up to 200 MPa. The sintering densification temperature and the starting threshold temperature of grain growth (T_sg) were determined by the applied pressure and the surface energy relative to grain size, as they were both observed to increase with grain size and to decrease with applied pressure. Densification with limited grain coarsening occurred under an applied pressure of 200 MPa at 1050 °C for the 220 nm Al₂O₃ powder and 1400 °C for the 3 μm Al₂O₃ powder. The grain boundary energy, residual stress, and dislocation density of the ceramics sintered under high pressure and low temperature were higher than those of the samples sintered without additional pressure. Plastic deformation occurring at the contact area of the adjacent particles was proved to be the dominant mechanism for sintering under high pressure, and a mathematical model based on the plasticity mechanics and close packing of equal spheres was established. Based on the mathematical model, the predicted relative density of an Al₂O₃ compact can reach ～80 % via the plastic deformation mechanism, which fits well with experimental observations. The densification kinetics were investigated from the sintering parameters, i.e., the holding temperature, dwell time, and applied pressure. Diffusion, grain boundary sliding, and dislocation motion were assistant mechanisms in the final stage of sintering, as indicated by the stress exponent and the microstructural evolution. During the sintering of the 220 nm alumina at 1125 °C and 100 MPa, the deformation tends to increase defects and vacancies generation, both of which accelerate lattice diffusion and thus enhance grain growth.     

keff uncertainty quantification and analysis due to nuclear data during the full lifetime burnup calculation for a small-sized prismatic high temperature gas-cooled reactor

To benefit from recent advances in modeling and computational algorithms,as well as the availability of new covariance data,sensitivity and uncertainty analyses are needed to quantify the impact of uncertain sources on the design parameters of small prismatic high-temperature gas-cooled reactors(HTGRs).In particular,the contribution of nuclear data to the keff uncertainty is an important part of the uncertainty analysis of small-sized HTGR physical calculations.In this study,a small-sized HTGR designed by China Nuclear Power Engineering Co.,Ltd.was selected for keff uncertainty analysis during full lifetime burnup calculations.Models of the cold zero power(CZP)condition and full lifetime burnup process were constructed using the Reactor Monte Carlo Code RMC for neutron transport calculation,depletion calculation,and sensitivity and uncertainty analysis.For the sensitivity analysis,the Contribution-Linked eigenvalue sensitivity/Uncertainty estimation via Track length importance Characterization(CLUTCH)method was applied to obtain sensitive infor-mation,and the"sandwich"method was used to quantify the keff uncertainty.We also compared the keff uncertainties to other typical reactors.Our results show that 235U is the largest contributor to keff uncertainty for both the CZP and depletion conditions,while the contribution of 239Pu is not very significant because of the design of low discharge burnup.It is worth noting that the radioactive capture reaction of 28Si significantly contributes to the keff uncer-tainty owing to its specific fuel design.However,the keff uncertainty during the full lifetime depletion process was relatively stable,only increasing by 1.12％owing to the low discharge burnup design of small-sized HTGRs.These numerical results are beneficial for neutronics design and core parameters optimization in further uncertainty prop-agation and quantification study for small-sized HTGR.     

基于IEC 60870-5-104协议的调度命令发送方法研究

对IEC 60870-5-104协议的调度命令进行了研究，提出了一种基于现有IEC 60870-5-104协议的调度命令发送新方法。此技术充分利用了IEC 60870-5-104协议的文件发送功能，通过远程终端单元（RTU）向电厂发送包含调度命令的文本文件。考虑到调度命令在电力系统和电力市场结算系统安全方面的重要性，将该方法应用在电网调度自动化 SCADA 系统中，可以实现交换数据的更高可用性。     

煤矿罗茨鼓风机的安装使用与故障分析

对罗茨鼓风机的特点、结构和工作原理进行了论述,对其安装使用与故障维修进行了归纳总结.在新型罗茨鼓风机的设计中,提出了一种由偏心孤和圆线曲线组合的三叶转子齿剖面,其在对新齿轮廓进行几何模型的基础上,提出了螺旋齿轮廓,并对啮合螺旋三叶进行了比较研究.结果 表明,新的螺旋齿轮廓可以创造更大的气流,降低鼓风机压力的峰值.     

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

Performance of Al2O3 particle reinforced glass-based seals in planar solid oxide fuel cells

Glass-based materials are usually considered as excellent seals for jointing adjacent components in planar solid oxide fuel cells, but the uncontrollable crystallization in the glass may cause delamination and micro-cracks in such seals. To solve this problem, Al2O3 ceramic particles were added to a BaO–CaO–Al2O3–B2O3–SiO2 glass system to reduce negative effects caused by crystalline phase on the gas tightness and the joint strength in the seals. At an operating temperature of 750 °C, the glass-based seals with 20 wt% Al2O3 addition (GA80) exhibited extremely low leakage rates (~0.002 sccm/cm under an input gas pressure of 13.6 kPa) and higher shear strength (3.31 MPa). The Al2O3 ceramic addition and the crystalline phase BaAl2Si2O8 reinforced the glass matrix. Further thermal cycle analyses indicated that leakage rates for the GA80 seals remained at around 0.0025 sccm/cm after 10 thermal cycles, which was consistent with minor microstructural change and good interface bonding. Single cell testing with of GA80 seals was performed and the results demonstrated stable electrochemical performance through 6 thermal cycles at an open circuit voltage of 1.16–1.18 V, as well as a power density above 546 mW/cm2 at a current density of 925 mA/cm2. These results showed the high thermal cycle stability of the glass/Al2O3 composite seals in intermediate temperature planar solid oxide fuel cells.     

Enhanced thermal shrinkage behavior of phenolic-derived carbon aerogel-reinforced by HNTs with superior compressive strength performance

A novel carbon/m-HNTs composite aerogel was synthesized by introducing the modified halloysite nanotubes (m-HNTs) into phenolic (PR) aerogels through chemical grafting, followed with carbonization treatment. In order to explore the best proportion of HNTs to phenolic, the micromorphology of PR/m-HNTs were investigated by SEM before carbonization, confirming 10 wt% of m-HNTs is most beneficial to the porous network of aerogels. The interaction between PR and HNTs was studied by FTIR spectra, and microstructure evolution of the target product-carbon/m-HNTs composite aerogel were illustrated by SEM and TEM techniques. SEM patterns indicated that the carbon/m-HNTs aerogels maintain a stable porous structure at 1000 °C (carbonization temperature), while a ~20 nm carbon layer was formed around m-HNTs generating an integral unit through TEM analysis. Specific surface area and pore size distribution of composite aerogels were analyzed based on mercury intrusion porosimetry and N₂ adsorption–desorption method, the obtained results stayed around 500 m²g^?1 and 1.00 cm³g^?1 (pore volume) without significant discrepancy, compared with pure aerogel, showing the uniformity of pore size. The weight loss rate (26.76%) decreased greatly compared with pure aerogel, at the same time, the best volumetric shrinkage rate was only 30.83%, contributed by the existence of HNTs supporting the neighbor structure to avoid over-shrinking. The highest compressive strength reached to 4.43 MPa, while the data of pure aerogel was only 1.52 MPa, demonstrating the excellent mechanical property of carbon/m-HNTs aerogels.     

50型螺旋式钢板仓卷边设备理论分析与试验

结合已有卷边设备的生产工艺和特点,研发了国内首台50型螺旋式钢板仓卷边设备,并完成了4次样机调试试验.分析了新型卷边设备关键机构的工作原理,对下轧辊调节机构进行了力学计算分析,完成了卷边孔型设计.利用显示动力学软件数值模拟了5 mm钢板的冷弯成形(卷边)过程,分析了成形过程中的等效应力和等效塑性应变.通过4次样机调试试验,将调试结果与模拟结果对比.结果 表明,折弯5 mm钢板比折弯3 mm的钢板力载荷大很多,有必要研发新型的卷边设备;卷边设备的后3个工位的应力峰值比前3个工位大,其中工位6应力峰值最大;文中的卷边孔型设计合理;卷边过程的模拟结果与试验结果一致.