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.     

微纳层叠聚丙烯腈凝胶流动特性的数值模拟研究

建立了层叠流道的三维模型和有限元网格模型，根据流变测试数据，采用Polymat对物料的黏度模型参数进行拟合，并利用Polyflow软件对聚丙烯腈（PAN）凝胶在层叠流道内的三维等温流动过程进行了数值模拟分析。研究发现，当入口流量增大时，层叠流道出口速度的不均匀性增加；沿流动方向流道内压力逐渐降低，并在出口处降低至同一最低值；流道进出口压力差与入口流量大小具有正相关性；在流道的中心截面上剪切速率分布均匀，波动较小。     

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.     

Turbulent boundary layer control with a spanwise array of DBD plasma actuators

The turbulent boundary layer control on NACA 0012 airfoil with Mach number ranging from 0.3 to 0.5 by a spanwise array of dielectric barrier discharge(DBD)plasma actuators by hot-film sensor technology is investigated.Due to temperature change mainly caused through heat produced along with plasma will lead to measurement error of shear stress measured by hot-film sensor,the correction method that takes account of the change measured by another sensor is used and works well.In order to achieve the value of shear stress change,we combine computational fluid dynamics computation with experiment to calibrate the hot-film sensor.To test the stability of the hot-film sensor,seven repeated measurements of shear stress at Ma = 0.3 are conducted and show that confidence interval of hot-film sensor measurement is from-0.18 to 0.18 Pa and the root mean square is 0.11 Pa giving a relative error 0.5％over all Mach numbers in this experiment.The research on the turbulent boundary layer control with DBD plasma actuators demonstrates that the control makes shear stress increase by about 6％over the three Mach numbers,which is thought to be reliable through comparing it with the relative error 0.5％,and the value is hardly affected by burst frequency and excitation voltage.     

催化剂级配技术在加氢改质装置上的工业应用

基于柴油产品质量升级的需求,中国石化大连石油化工研究院(FRIPP)开发了FHIDW加氢改质技术及配套FF-46加氢精制催化剂、FC-14B加氢改质催化剂和FDW-3临氢降凝催化剂.该技术及催化剂级配体系在格尔木炼油厂0.8 Mt·a-1加氢改质装置上的工业应用情况表明,级配催化剂体系对原料适应性强,装置运转平稳,操作灵活性高,催化剂失活速率慢,产品分布合理且质量优异,在降低柴油产品凝点的同时可以明显改善其密度和十六烷值,解决了改造前装置生产重柴油密度偏低的问题,为炼油厂生产符合国V质量标准的柴油提供了技术保障.     

课程思政在现代学徒制煤化工专业课程中的教学探索——以"煤质分析及煤化工产品检验"课程为例

现代学徒制是一项深化产教融合、校企合作的育人机制,是创新技术技能人才的现代培养模式.山西铁道职业技术学院与山西安泰控股集团有限公司深度合作开展山西省现代学徒制试点项目,合作目的之一是培养企业煤化工专业人才.学校教师结合学生(员工)在企业车间岗位上的技能知识,系统地讲授煤化工专业课程"煤质分析及煤化工产品检验"理论知识,同时针对企业员工日常学习思想政治知识较少的实际,润物细无声地加入思政元素,实现专业知识与实践技能相结合,技能知识与思政教育相融合,真正培养知识型、技能型、创新型高素质技能人才,努力构建职业教育产业发展命运共同体.     

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。     

一类分数阶微积分的中值定理及应用

Riemann-Liouville分数阶微积分算子是一类带有一个函数的分数阶微积分算子的特殊情形，以Riemann-Liouville分数阶微积分算子的积分中值定理和微分中值定理为基础，我们得到了一类带有一个函数的分数阶微积分算子的积分中值定理和微分中值定理，并给出其在计算方面的一些应用。     

基于GA-BP的汽车风振噪声声品质预测模型

目前对于汽车风振噪声的优化研究主要以声压级（Sound pressure level，SPL）作为单一评价指标，既不能全面反映噪声的物理属性，也无法考虑人耳对噪声的主观认知过程。为准确评价风振噪声，引入声品质，运用大涡模拟（Large eddy simulation，LES）对风振噪声进行数值仿真，根据实车道路试验判断仿真的准确性；对仿真结果进行声品质客观评价与主观评价，综合声品质客观评价参数与声品质主观评价试验结果建立BP神经网络预测模型；利用遗传算法（Genetic algorithm，GA），进一步对BP神经网络的结构参数进行优化，建立GA-BP声品质预测模型。研究结果表明，GA-BP声品质预测模型在训练速度和预测精度上都优于BP神经网络预测模型。预测模型基于声品质主客观评价结果，其预测值可以代替传统的声压级评价指标，为风振噪声提供更为准确合理的评价。