Identification of Novel Fragments Binding to the PDZ1-2 Domain of PSD-95

Inhibition of PSD-95 has emerged as a promising strategy for the treatment of ischemic stroke, as shown with peptide-based compounds that target the PDZ domains of PSD-95. In contrast, developing potent and drug-like small molecules against the PSD-95 PDZ domains has so far been unsuccessful. Here, we explore the druggability of the PSD-95 PDZ1-2 domain and use fragment screening to investigate if this protein is prone to binding small molecules. We screened 2500 fragments by fluorescence polarization (FP) and validated the hits by surface plasmon resonance (SPR), including an inhibition counter-test, and found four promising fragments. Three ligand efficient fragments were shown by ¹H,¹⁵N HSQC NMR to bind in the small hydrophobic P⁰ pockets of PDZ1-2, and one of them underwent structure-activity relationship (SAR) studies. Overall, we demonstrate that fragment screening can successfully be applied to PDZ1-2 of PSD-95 and disclose novel fragments that can serve as starting points for optimization towards small-molecule PDZ domain inhibitors.     

Matrix Manipulation of Directly-Synthesized PbS Quantum Dot Inks Enabled by Coordination Engineering

The direct-synthesis of conductive PbS quantum dot (QD) ink is facile, scalable, and low-cost, boosting the future commercialization of optoelectronics based on colloidal QDs. However, manipulating the QD matrix structures still is a challenge, which limits the corresponding QD solar cell performance. Here, for the first time a coordination-engineering strategy to finely adjust the matrix thickness around the QDs is presented, in which halogen salts are introduced into the reaction to convert the excessive insulating lead iodide into soluble iodoplumbate species. As a result, the obtained QD film exhibits shrunk insulating shells, leading to higher charge carrier transport and superior surface passivation compared to the control devices. A significantly improved power-conversion efficiency from 10.52% to 12.12% can be achieved after the matrix engineering. Therefore, the work shows high significance in promoting the practical application of directly synthesized PbS QD inks in large-area low-cost optoelectronic devices.     

基于纸喷雾离子化衍生质谱法快速检测PM2.5中的醌污染物

醌类化合物是PM2.5中的一类有害物质。本研究建立了纸喷雾离子化衍生质谱法快速测定PM2.5中的醌类污染物。通过衍生化反应在醌化合物中引入氨基，提高醌在纸喷雾中的离子化效率。随后对衍生化试剂种类、电压、喷雾溶剂种类等反应条件进行优化。在最优实验条件下，采用内标法定量分析1,4-苯醌、甲基对苯醌、1,4-萘醌和1,4-蒽醌，4种化合物均呈现较好的线性关系，其检出限分别为4.49、20.89、0.13、0.17 ng。利用该方法分析PM2.5实际样品中的萘醌和蒽醌，均获得了较好的定性和定量结果。     

浅谈压力铸造的全自动化生产

近年来,国家对制造业的数字化、网络化、智能化越来越重视,特别是《中国制造2025》的发布,更是促进整个制造业向智能制造迈进,铸造行业也应该紧跟步伐。在传统压力铸造行业中压铸机的加料、取件,切边机的上件、下件,加工机床的上件、下件,都是依靠人来完成,大大制约了行业的发展。本文阐述了压力铸造的全自动化生产,为压力铸造行业的转型升级提供借鉴。     

当代青年在新冠肺炎疫情防控中的社会责任担当研究

面对新冠肺炎疫情,多数青年积极进取、富有创造力和责任心,少数青年缺乏应有的担当意识.文章分析了当代青年社会责任感缺失的成因,提出了青年社会责任担当意识养成的举措.     

工艺参数对动态流量控制法挤压弯管应力的影响

采用有限元模拟和实验研究了挤压钛合金弯曲管件。通过实验验证了工件的形状和尺寸精度,并通过有限元模拟分析了工艺参数对挤出过程中变形体的平均压应力分布情况和挤出弯管件的曲率半径的影响规律。结果表明:有限元模拟中,弯管件的曲率半径误差为6.03%,弯管直径误差为3.82%;在靠近定径带处,平均压应力呈非均匀分布;在焊合腔内,靠近细分流孔区域的平均压应力小于靠近粗分流孔区域的平均压应力,平均压应力的大小顺序在通过粗、细分流孔前后相反;在模具结构固定不变时,弯管件的曲率半径随挤压速度的减小而增大,不随挤压温度的变化而变化。     

用COMSOL实现圆波导中电磁波的可视化

为了直观描述金属圆波导中电磁场复杂的空间分布,本文用Comsol软件对金属圆波导中的TE11模、TE01模、和TM01模的电磁场结构进行动态仿真.将电磁场中的抽象概念形象化、可视化,使学生看清电磁场分布的宏观概况和细节变化,开拓了视野,同时加深了学生对电磁波传播特性的理解.     

双螺旋线圆柱凸轮机构的设计与分析

以应某企业要求设计一款用于机械手臂端部完成螺旋高速往复的机构,介绍了双滚子在螺旋线圆柱凸轮上的应用.采用解析法对机构的受力以及运动进行理论分析.利用NX10.0建模,将模型导入Adams2016输出其运动数据,对解析法结果进行验证.对设计初期得到的滚子与螺旋切槽的接触冲击进行分析,针对双滚子在运作时对螺旋切槽造成冲击大、晃动剧烈、部分零件磨损严重等问题,对圆柱凸轮机构进行优化改进,利用Adams2016软件对滚子的运动进行模拟分析.分析运算后的结果验证了改进后的机构在很大程度上实现了增加双滚子螺旋运动的平稳性能,更好的实现了双滚子与凸轮槽之间的拟合,实现了机构的平稳、高效运行.     

直升机主旋翼离心上限动器损伤解决措施

旋翼作为直升机关键动部件之一,其健康状态直接关系到直升机的安全性与可靠性.针对直升机主旋翼离心上限动器的损伤问题,通过机理分析、运动仿真确定其损伤原因,制定改进措施并通过了试飞验证,对国内直升机技术的发展具有积极促进性作用.     

爆炸冲击波载荷下预制孔铝板的动态响应

为研究爆炸冲击波对破片穿孔后板结构的毁伤效应,使用激波管为冲击波加载设备,对不同孔形的预制孔铝板进行冲击波加载.利用三维数字图像相关(3 D-DIC)技术,分析固支预制孔方形铝板在冲击波加载条件下的动态响应,得到预制孔铝板的动态响应和变形失效过程.结合3 D-DIC结果分析孔形对靶板刚度、破坏形式、承载能力的影响.结果表明:圆形孔靶板刚度最大,圆形孔靶板的极限承载能力最大,菱形孔靶板极限承载能力最差;孔形对撕裂破坏的影响主要体现在孔的角点在靶板分布上.该实验结果对固支板结构的抗爆设计具有一定参考价值.