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1.
Dr. Jie Zang Dr. Fei Ye Dr. Sara M. Ø. Solbak Dr. Lars J. Høj Prof. Mingjie Zhang Prof. Anders Bach 《ChemMedChem》2021,16(6):949-954
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. 相似文献
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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... 相似文献
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碰撞冲击连接凭借其优异的连接性能得到广泛关注. 为探讨小端面冲击连接效应,首先从冲击焊的连接界面形貌出发,探讨冲击连接界面形貌对力学性能的影响,指出波浪形界面对可靠接头的重要性,并从大端面冲击连接的过程进一步讨论波浪形界面的形成机理,在此基础上讨论小端面冲击连接的波浪形界面形成机理,指出人为设置的带倾角的碰撞是形成小端面波浪形界面的前提,同时提出解决小端面带倾角碰撞所出现的非对称问题的有效方法是将复板连接端面改为锥形端面. 相似文献
4.
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. 相似文献
5.
Yuguang Chao Peng Zhou Jianping Lai Weiyu Zhang Huawei Yang Shiyu Lu Hui Chen Kun Yin Menggang Li Lu Tao Changshuai Shang Meiping Tong Shaojun Guo 《Advanced functional materials》2021,31(24):2100923
Designing a semiconductor-based heterostructure photocatalyst for achieving the efficient separation of photogenerated electron-hole pairs is highly important for enhancing H2 releasing photocatalysis. Here, a new class of Ni1−xCoxSe2–C/ZnIn2S4 hierarchical nanocages with abundant and compact ZnIn2S4 nanosheets/Ni1−xCoxSe2 C nanosheets 2D/2D hetero–interfaces, is designed and synthesized. The constructed heterostructure photocatalyst exposes rich hetero-junctions, supplying the broad and short transfer paths for charge carriers. The close contacts of these two kinds of nanosheets induce a strong interaction between ZnIn2S4 and Ni1−xCoxSe2 C, improving the separation and transfer of photo-generated electron-hole pairs. As a consequence, the distinctive Ni1−xCoxSe2 C/ZnIn2S4 hierarchical nanocages without using additional noble-metal cocatalysts, display remarkable H2-relaesing photocatalytic activity with a rate of 5.10 mmol g−1 h−1 under visible light irradiation, which is 6.2 and 30 times higher than those of fresh ZnIn2S4 nanosheets and bare Ni1−xCoxSe2 C nanocages, respectively. Spectroscopic characterizations and theory calculations reveal that the strong interaction between ZnIn2S4 and Ni1−xCoxSe2 C 2D/2D hetero-interfaces can powerfully promote the separation of photo-generated charge carriers and the electrons transfer from ZnIn2S4 to Ni1−xCoxSe2 C. 相似文献
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The slight-alkalization of generator internal cooling water (GICW) is widely used to inhibit the corrosion of hollow copper conductor and thereby ensure the safe operation of the generator. CO2 inleakage is increasingly identified as a potential security risk for GICW system. In this paper, the influence of CO2 inleakage on the slight-alkalization of GICW was theoretically discussed. Based on the equilibriums of the CO2-NaOH-H2O system, CO2 inleakage saturation was derived to quantify the amount of the dissolved CO2 in GICW. This parameter can be directly calculated with the measured conductivity and the [Na+] of GICW. The influence of CO2 inleakage on the slight-alkalization conditioning of GICW and the measurement of its water quality parameters were then analyzed. The more severe the inleakage, the narrower the water quality operation ranges of GICW, resulting in the more difficult the slight-alkalization conditioning of GICW. The temperature calibrations of the conductivity and the pH value of GICW show non-linear correlations with the amount of CO2 inleakage and the NaOH dosage. This study provides insights into the influence of CO2 inleakage on the slight-alkalization of GICW, which can serve as the theoretical basis for the actual slight-alkalization when CO2 inleakage occurs. 相似文献
10.
盾构隧道施工物料无人运输有助于提升运输效率、降低运输成本、减少运输安全事故率。与公路汽车无人驾驶、港口车辆无人驾驶、轨道交通无人驾驶等逐步成熟的无人驾驶技术不同,在隧道场景下实施施工物料无人运输存在运输物料种类繁多、运输调度困难、地下定位信号拒止、狭窄车道频繁会车、行车路面工况复杂、地上地下联动响应慢等诸多挑战。从实现盾构隧道施工物料无人运输的关键问题分析入手,综述当前盾构隧道施工物料运输方式、运输需求、无人运输发展现状及存在的挑战,提出盾构隧道施工物料无人运输的五大关键技术:多种类物料智能货控能效管理技术,无人化垂直装卸门机控制技术,多传感器融合同步定位与地图构建技术,隧道复杂环境路径规划与自主避障技术,隧-地一体化联动响应的高可靠性无线通信技术。 相似文献