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。     

M2M energy saving strategy in 5G millimeter wave system

Telecommunication Systems - Machine to Machine technology has a broad application prospect in the 5G network, but there is a bottleneck in the energy consumption of intelligent devices powered by...     

某工业园区污水处理厂升级改造工程案例分析

以河北某园区污水处理厂提标改造工程为研究对象,通过对污水厂来水组成调研、取样、化验分析、试验,确定水解酸化+MBR+臭氧催化氧化组合工艺为主要设计方案.根据调试及运行结果,MBR组合工艺系统运行稳定,出水达到《地表水环境质量标准》(GB 3838—2002)地表水Ⅳ类标准(除TN外),根据长期实际运行效果,出水CODCr≤30 mg/L、氨氮≤1 mg/L、TN≤10 mg/L、TP≤10 mg/L,SS≤0.7 mg/L,出水回用于当地景观水体.本项目的设计与实施为类似工业园区污水处理厂尤其是存在较高难降解有机物、TN去除率要求高的污水厂提标改造提供了参考经验.     

Effect of nitriding atmosphere on the morphology of AlN nanofibers from solution blow spinning

High purity AlN fiber is a promising thermal conductive material. In this work, AlN fibers were prepared using solution blow spinning followed by nitridation under N₂ or NH₃ atmosphere. Soluble polymer, such as polyaluminoxane, and allyl-functional novolac resin were adopted as raw materials to form homogeneous distribution of Al₂O₃ and C nanoparticles within the fibers, which could inhibit the growth of alumina crystal and promote their nitridation process. The effect of nitriding atmosphere on the fiber morphology was investigated. XRD results showed that complete nitridation was achieved at 1300 °C in the NH₃ or at 1500 °C in the N₂ atmosphere. Hollowed fiber structure was observed when fiber was nitrided in N₂ at high temperature, which was caused by gaseous Al gas diffusion, and this phenomenon was eliminated in NH₃ atmosphere. The nitridation mechanisms in different atmosphere were analyzed in detail. It was demonstrated that the nitridation of Al₂O₃ fibers in the NH₃ atmosphere offered the favored AlN morphology and chemical quality. Flexible AlN fiber with O content of 0.7 wt% was achieved after nitriding in NH₃ at 1400 °C. The high quality AlN can be used in thermal conductive composite materials.     

ZIF衍生氧还原反应催化剂的研究进展

从沸石咪唑酯骨架材料(ZIF)衍生的含过渡金属催化剂出发,介绍ZIF衍生催化剂前驱体的制备和热解温度、气氛对催化剂的影响,总结ZIF衍生的铂和非贵金属催化剂材料用于氧还原反应(ORR)的研究进展.提出有关ZIF衍生ORR催化剂发展面临的实际应用挑战和活性位点探究问题.     

企业思想政治教育系统设计

为进一步提升企业思想政治教育工作的信息化水平,本文详细介绍了企业思想政治教育系统的数据库设计方案,以便更加充分地发挥各种多媒体教学设备在企业思想政治教育工作方面的优势。     

激光在线测厚振动分析与精度优化

激光测厚具有安全可靠、测量精度高、测量范围大等优点,广泛应用于纸张、电池极片等薄膜类材料厚度的在线测量。带材宽幅方向扫描测厚时由于扫描架往复运动会产生机械振动,影响在线测厚精度。针对该问题,以锂离子电池极片厚度测量为例,使用双激光差动式测厚平台对电池极片和铜箔分别进行厚度测量,然后对测厚数据进行频谱分析,探究其振动规律的相似性,并基于频谱分析结果采用滑动带阻滤波方式对测厚数据进行处理,滤波后极片和铜箔的厚度极差分别降低了33.4%和73.8%,有效过滤了机械振动导致的测量误差,可满足极片和铜箔厚度测量的精度要求。