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.     

乘用车悬架静强度与疲劳载荷研究

为了快速获得平台悬架静强度与疲劳载荷,本文依据某A级平台5款量产车型试验场道路栽荷数据,以前麦弗逊悬架为研究对象,先对轮心载荷幅值进行统计分析,根据应力-强度干涉模型,得到该平台前悬架的强度载荷边界,及其与车辆满载轮荷的G载荷系数.再通过研究5款车型车轮轮心疲劳伪损伤与轮荷的关联关系,得到该平台悬架的疲劳栽荷.此方法可快速获得同平台悬架静强度与疲劳载荷,省去实车道路谱采集并提升了工作效率.     

机井自动化供水方案改进

针对民乐县农村人饮机井水位自动供水系统控制中存在的可靠性低、成本高等问题,文章结合深井泵提取地下水进行供水的实际情况,提出了软启动控制柜+浮球开关+微电脑时间控制器改进的思路和方法,运用效果良好。     

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。     

机器翻译译文质量估计综述

机器翻译译文质量估计(Quality Estimation,QE)是指在不需要人工参考译文的条件下,估计机器翻译系统产生的译文的质量,对机器翻译研究和应用具有很重要的价值。机器翻译译文质量估计经过最近几年的发展,取得了丰富的研究成果。该文首先介绍了机器翻译译文质量估计的背景与意义;然后详细介绍了句子级QE、单词级QE、文档级QE的具体任务目标、评价指标等内容,进一步概括了QE方法发展的三个阶段: 基于特征工程和机器学习的QE方法阶段,基于深度学习的QE方法阶段,融入预训练模型的QE方法阶段,并介绍了每一阶段中的代表性研究工作;最后分析了目前的研究现状及不足,并对未来QE方法的研究及发展方向进行了展望。     

Adaptive Synchronization-Based Approach for Finite-Time Parameters Identification of Genetic Regulatory Networks

Neural Processing Letters - This paper presents an approach to identify the unknown parameters of genetic regulatory network (GRN) in finite-time. The adaptive synchronization-based method is used...     

水泥窑烟气脱硫系统节能降耗措施探讨

水泥窑烟气为满足高硫条件下排放达标，多采用窑灰-石膏湿法烟气脱硫。其工艺系统相对复杂，在脱除SO2的同时，要消耗水、电等资源，因此，节能降耗对提升脱硫系统的经济性具有重要意义。本文通过对水、电从工艺、设备选型和运行维护三方面探讨了水泥窑烟气脱硫系统节能降耗措施。