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1.
Amides from indole-3-glyoxylic acid and 4-benzoyl-2-methylpiperazine, which are related to entry inhibitors developed by Bristol-Myers Squibb (BMS), have been synthesized with aliphatic chains located at the C7 position of the indole ring. These spacers contain an azido group suitable for the well-known Cu(I)-catalyzed (3+2)-cycloaddition or an activated triple bond for the nucleophilic addition of thiols under physiological conditions. Reaction with polyols (β-cyclodextrin and hyperbranched polyglycerol) decorated with complementary click partners has afforded polyol-BMS-like conjugates that are not cytotoxic (TZM.bl cells) and retain the activity against R5-HIV-1NLAD8 isolates. Thus, potential vaginal microbicides based on entry inhibitors, which can be called of 4th generation, are reported here for the first time.  相似文献   
2.
Spinal muscular atrophy (SMA) is an autosomal recessive hereditary neuromuscular disease. Exon 7 and 8 of survival of motor neuron 1 (SMN1) gene or only exon 7 homology deletion leads to the failure to produce a full-length SMN gene. The copy number of SMN2 gene with high homology of SMN1 affects the degree of disease and was the target gene for targeting therapy, in which splicing silencer in intron 7 was the key to suppress the inclusion of exon 7. In this study, we projected to use CRISPR/Case 9 for the targeted editing of intronic-splicing silencer (ISS) sequence to promote the inclusion of SMN2 exon 7 and increase the production of SMN2 full-length (FL) gene expression. It happens that there was a protospacer adjacent motif (PAM) at one end of the ISS sequence according to the design of sgRNA. The recombinant vector of sgRNA HSMN2 CRISPR/Case 9 was constructed and transfected into HEK293 cells. Sequencing results showed that the ISS sequence could be edited accurately and targeting in the predicted direction, in which deleting small fragments, inserting small amounts and mutation. Quantitative analysis of RT-PCR products by restriction enzyme of DdeI digestion showed that the FL of SMN2 increased by 8% (P < 0.05). In the primary cultured chondrocytes of SMA mice, in which sgRNA HSMN2 CRISPR/Case9 recombinant vector transfection could increase the SMN2 FL gene by 23% (P < 0.05) and significantly improve SMN protein levels (P < 0.05). CRISPR/Case 9 is an effective tool for gene editing and therapy of hereditary diseases, but it is rarely reported in the treatment of SMA diseases. This study shows that CRISPR/Case 9 was first used for the precision target of ISS sequence editing, which can effectively promote the production of SMN2 FL gene expressions, in which there was an important clinical reference value.  相似文献   
3.
The substantial increase in DNA sequencing efforts has led to a rapid expansion of available sequences in glycoside hydrolase families. The ever-increasing sequence space presents considerable opportunities for the search for enzymes with novel functionalities. In this work, the sequence-function space of glycoside hydrolase family 94 (GH94) was explored in detail, using a combined approach of phylogenetic analysis and sequence similarity networks. The identification and experimental screening of unknown clusters led to the discovery of an enzyme from the soil bacterium Paenibacillus polymyxa that acts as a 4-O-β-d -glucosyl-d -galactose phosphorylase (GGalP), a specificity that has not been reported to date. Detailed characterization of GGalP revealed that its kinetic parameters were consistent with those of other known phosphorylases. Furthermore, the enzyme could be used for production of the rare disaccharides 4-O-β-d -glucosyl-d -galactose and 4-O-β-d -glucosyl-l -arabinose. Our current work highlights the power of rational sequence space exploration in the search for novel enzyme specificities, as well as the potential of phosphorylases for rare disaccharide synthesis.  相似文献   
4.
We propose a self-sustaining power supply system consisting of a “Hybrid Energy Storage System (HESS)” and renewable energy sources to ensure a stable supply of high-quality power in remote islands. The configuration of the self-sustaining power supply system that can utilize renewable energy sources effectively on remote islands where the installation area is limited is investigated. It is found that it is important to select renewable energy sources whose output power curve is close to the load curve to improve the efficiency of the system. The operation methods that can increase the cost-effectiveness of the self-sustaining power supply system are also investigated. It is clarified that it is important for increasing the cost effectiveness of the self-sustaining power supply system to operate the HESS with a smaller capacity of its components by setting upper limits on the output power of the renewable energy sources and cutting the infrequent generated power.  相似文献   
5.
The hydrolysis of sodium borohydride (NaBH4) over catalysts is a promising method to produce hydrogen. Although Co-based catalysts exhibit high activity for NaBH4 hydrolysis, they are still far from satisfying practical applications, especially their poor durability in alkaline media. Herein, a carbon shell structure was designed and synthesized to improve the stability of the mixture of Co0 and CoxOy nanofilms (Co/CoxOy@C) during NaBH4 hydrolysis via a facile polymerization-pyrolysis strategy with Co/CoxOy nanofilms as the precursor. As a result, the Co/CoxOy@C catalyst can achieve a remarkable H2 generation rate of 4348.6 mL min?1 gCo?1 with a low activation energy of 43.6 kJ mol?1, which is superior to most previously reported catalysts. Moreover, the catalyst shows high stability with an H2 generation-specific rate of 79% after five cycles. The excellent performance of carbon substrate can well prevent the agglomeration of Co-based nanoparticle and improve the corrosion resistance of the active Co to BO2? and OH?. This work would widen the road for the preparation of nanoconfined catalysts, which has prospective application potentials for H2 production from NaBH4 hydrolysis.  相似文献   
6.
This article addresses an investigation of the entropy analysis of Williamson nanofluid flow in the presence of gyrotactic microorganisms by considering variable viscosity and thermal conductivity over a convectively heated bidirectionally stretchable surface. Heat and mass transfer phenomena have been incorporated by taking into account the thermal radiation, heat source or sink, viscous dissipation, Brownian motion, and thermophoretic effects. The representing equations are nonlinear coupled partial differential equations and these equations are shaped into a set of ordinary differential equations via a suitable similarity transformation. The arising set of ordinary differential equations was then worked out by adopting a well-known scheme, namely the shooting method along with the Runge-Kutta-Felberge integration technique. The effects of flow and heat transfer controlling parameters on the solution variables are depicted and analyzed through the graphical presentation. The survey finds that magnifying viscosity parameter, Weissenberg number representing the non-Newtonian Williamson parameter cause to retard the velocity field in both the directions and thermal conductivity parameter causes to reduce fluid temperature. The study also recognizes that enhancing magnetic parameters and thermal conductivity parameters slow down the heat transfer rate. The entropy production of the system is estimated through the Bejan number. It is noticeable that the Bejan number is eminently dependent on the heat generation parameter, thermal radiation parameter, viscosity parameter, thermal conductivity parameter, and Biot number. The skillful accomplishment of the present heat and mass transfer system is achieved through the exteriorized choice of the pertinent parameters.  相似文献   
7.
A novel image sequence-based risk behavior detection method to achieve high-precision risk behavior detection for power maintenance personnel is proposed in this paper. In this method, the original image sequence data is first separated from the foreground and background. Then, the free anchor frame detection method is used in the foreground image to detect the personnel and correct their direction. Finally, human posture nodes are extracted from each frame of the image sequence, which are then used to identify the abnormal behavior of the human. Simulation experiment results demonstrate that the proposed algorithm has significant advantages in terms of the accuracy of human posture node detection and risk behavior identification.  相似文献   
8.
Machine learning-based fault detection methods are frequently combined with wavelet transform (WT) to detect an unintentional islanding condition. In contrast to this condition, these methods have long detection and computation time. Thus, selecting a useful signal processing-based approach is required for reliable islanding detection, especially in real-time applications. This paper presents a new modified signal processing-based islanding detection method (IDM) for real-time applications of hydrogen energy-based distributed generators. In the study, a new IDM using a modified pyramidal algorithm approach with an undecimated wavelet transform (UWT) is presented. The proposed method is performed with different grid conditions with the presence of electric noise in real-time. Experimental results show that oscillations in the acquired signal can be reduced by the UWT, and noise sensitivity is lower than other WT-based methods. The non-detection zone is zero and the maximum detection and computational time is also 75 ms at a close power match.  相似文献   
9.
Significant efforts have been made to develop highly active non-noble metal-based, affordable metallic and stable electro-catalysts for hydrogen evolution reaction (HER). Strong acid and bases are now used in HER operations to achieve large-scale, sustained H2 fuel production. However, few studies have utilized phosphate-buffered neutral electrolytes (PBS) in the field of neutral electrolyte technology. In this work, a certain alloys with a Ni–Cr basis have been produced as favorable components for the HER under neutral conditions. Additionally, the current investigations are emphasizing on the concentration of buffer phosphate species in the HER activity of various materials. By employing polarization and electrochemical impedance spectroscopy (EIS) in neutral solutions, the electro-catalytic activity of new alloys on HER was evaluated. According to the preliminary findings, the examined Ni–Cr-based alloys show superior HER catalytic activity in neutral electrolytes. Additionally, the Ni–Cr alloy matrix with Fe and Mo added enhances HER electrocatalytic efficiency while lowering interfacial charge transfer resistance. Due to its low overpotential of ?297 mV @ 10 mA cm?2 and Tafel slope of 94 mV dec?1 in 1.0 M PBS media, the Ni–Cr–Mo–Fe alloy exhibits an efficient HER, suggesting that the Ni–Cr–Mo–Fe electrode will be a potential noble metal-free electro-catalyst for HER. The Ni–Cr–Mo–Fe cathode is a readily available and affordable material for the production of HER in neutral medium.  相似文献   
10.
光伏发电功率存在波动性,且光伏出力易受各种气象特征影响,传统TCN网络容易过度强化空间特性而弱化个体特性。针对上述问题,文中提出一种基于VMD和改进TCN的短期光伏发电功率预测模型。通过VMD将原始光伏发电功率时间序列分解为若干不同频率的模态分量,将各个模态分量以及相对应的气象数据输入至改进TCN网络进行建模学习。利用中心频率法确定VMD的最优分解模态分解个数。在传统TCN预测模型的基础上,使用DropBlock正则化取代Dropout正则化以达到抑制卷积层中信息协同的效果,并引入注意力机制自主挖掘并突出关键气象输入特征的影响,量化各气象因素对光伏发电的影响,从而提高预测精度。以江苏省某光伏电站真实数据为例进行仿真实验,结果表明所提预测方法的RMSE为0.62 MW,MAPE为2.03%。  相似文献   
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