New inhibitors of the Tat-TAR RNA interaction found with a "fuzzy" pharmacophore model

TAR RNA is a potential target for AIDS therapy. Ligand-based virtual screening was performed to retrieve novel scaffolds for RNA-binding molecules capable of inhibiting the Tat-TAR interaction, which is essential for HIV replication. We used a "fuzzy" pharmacophore approach (SQUID) and an alignment-free pharmacophore method (CATS3D) to carry out virtual screening of a vendor database of small molecules and to perform "scaffold-hopping". A small subset of 19 candidate molecules were experimentally tested for TAR RNA binding in a fluorescence resonance energy transfer (FRET) assay. Both methods retrieved molecules that exhibited activities comparable to those of the reference molecules acetylpromazine and chlorpromazine, with the best molecule showing ten times better binding behavior (IC50 = 46 microM). The hits had molecular scaffolds different from those of the reference molecules.     

Hybrid systems in seawater desalination—practical design aspects, present status and development perspectives

Ever since seawater desalination has been applied on an industrial scale, and particular in the countries of the Arabian Gulf, the application of desalination processes in dual-purpose facilities—water and power—as a hybrid configuration has been discussed in many feasibility investigations and also planning concepts. It is above all the combination of reverse osmosis with thermal processes that has found increasing interest with the aim of ensuring, as economically as possible, uniform water supplies under the specific, greatly varying load conditions in the Gulf countries. Such design concepts for hybrid configurations encompass straightforward structures with a low degree of coupling between membrane and thermal desalination processes, but range up to very complex configurations with strong interconnections on both the water side and thermally, as well as with several desalination processes connected in series or in parallel. Classical hybrid concepts in which the permeate from an RO desalination component is mixed with distillate from thermal desalination have already been implemented in Saudi Arabian dual-purpose plants, like Jeddah and Yanbu-Medina. Although hybrid systems of greater complexity have been addressed in many design studies and publications, up to now none has been brought to fruition. Coming into consideration asthe design basis for determining the capacity shares of the various desalination processes operated in a hybrid configuration are: arrangement of thermal cycle of the power plant component; water/power ratio of the dual-purpose seawater desalination and power plant; provision of undiminished water production of the desalination plant as electricity generation varies; provision of a specified drinking water quality with regard to composition and salt content; combination of all these aspects. Also gaining in importance are concerns of environmental pollution and sustainable development when selecting seawater desalination and power plant configurations, as well as their optimization when considering desalination and electricity generation as a whole. In the practical design of hybrid membrane and thermal systems, aspects come to light, though, that restrict linking of the two systems and joint utilization of facilities, as conceived in studies and conceptual design investigations. This applies both for common utilization of intakes and the use of heated up cooling water from thermal processes as a feed stream for the RO part of the desalination process. Additionally, requirements of drinking water composition, particularly chloride content, TDS and compliance with a specific residual content of boron, influence specifically the design of the membrane process part and its share in the total desalination capacity. Such practical aspects have greatly influenced the design and configuration of the Fujairah hybrid plant for which, from a total desalination capacity of 100 MIGD (454,600 m³/d), the share of 37.5 MIGD (170,500 m³/d) makes its seawater RO plant the biggest currently being constructed anywhere in the world. From the findings of the engineering of this plant and the idea that, by increasing interconnection between the two processes on the water side, it is possible to advance a hybrid configuration of this type with regard to cost optimization in the membrane installation, but also by joint utilization of the intake equipment, perspectives result for applied research efforts over the near and long terms, for example: long-term behavior of membranes at elevated temperatures; tendency for biofouling in membrane process with common utilization of cooling water and brine; influences of such interconnections on the overall availability of the facility. But also for the operation and maintenance organization of such large facilities, consequences can be foreseen for the future development of hybrid plants, particularly for operation management and organisation of the interplay of the different power plant and desalination systems, monitoring of SWRO membrane replacement and cleaning, as well as controlling water quality.     

设计降雨特征对城市内涝模拟结果的影响分析

降雨是城市内涝的主要诱因之一,不同降雨特征对于城市内涝风险的影响也有所区别。为了进一步挖掘降雨特征对城市内涝风险的影响,采用综合流域排水模型（InfoWorks ICM）构建了我国南方某城市的内涝模型,系统分析了设计降雨的雨型和历时特征对城市内涝模拟结果的影响。在4个重现期的3种降雨雨型和3个降雨历时条件下,共计36个不同降雨情景对研究区的内涝情况进行模拟。通过对比不同模拟情景下的积水深度、积水面积以及积水量等结果发现：在相同降雨雨型和重现期条件下,降雨历时对积水深度的影响有一定的差别;在不同降雨雨型和降雨历时模拟情景中,积水点的位置基本保持一致,而积水面积受降雨雨型和降雨历时的双重影响;峰值积水量受降雨雨型影响较大,受降雨历时影响较小,而积水总量受降雨历时影响较大,受降雨雨型影响较小。研究中量化分析了不同设计降雨特征对城市内涝模拟结果的影响,旨在为合理地开展城市内涝预警以及应急管理等工作提供依据。     

对辊式造粒机的设计与应用

对辊式造粒机用来生产复混肥 ,采用无干燥工艺流程 ,常温生产 ,产品一次成型 ,工艺设计合理、技术可行。既可生产低、中、高浓度复混肥料 ,也可生产单质颗粒磷肥 ,大颗粒碳铵等多品种肥料     

防腐蚀涂装系统设计

介绍了防腐蚀涂装设计的影响因素，涂料产品的相关文件以及确立防腐蚀涂装设计应考虑的基本原理和情况。     

天冬甜精中间体的合成优化

用均匀设计法优化了天冬甜精中间体———N 乙氧硫羰基天冬氨酸的合成反应条件。优化工艺条件为 :反应温度 72℃ ,n(甲基乙基黄原酸酯 )∶n(天冬氨酸 ) =1 5 0∶1 0 0 ,m(天冬氨酸 )∶m(氢氧化钠 ) =0 5 0∶1 0 0 ,m(水 )∶m(天冬氨酸 ) =4 0 0∶1 0 0 ,m(甲醇 )∶m(水 ) =0 15∶1 0 0。N 乙氧硫羰基天冬氨酸的收率为 88 92 %。     

萃取精馏溶剂选择的研究进展

本文概括论述了萃取精馏过程中影响溶剂选择的因素，在此基础上着重介绍了溶剂的选择方法，性质约束方法可分为：试验法，经验筛选和活度系数法；计算机优化方法可分为计算机辅助分子设计法和人工神经网络法，对上述方法的适用性作了详细的讨论。     

新形势下做好长江流域水土保持监测工作的思考

基于长江流域水土保持的监测调研工作,结合我国当前社会、经济发展新形势的总体要求,针对开展好流域水土保持监测工作这一课题,从完善水土流失动态监测工作、构建应急监测体系、强化机构职能定位、推进先进技术和设施设备应用、优化流域网络体系顶层设计、探究水土流失监测综合性指标设置等方面开展了一些有益的探索,以利于更好地开展新形势下的水土保持监测工作。     

塑料挤出成型模具流道优化设计

本文依据流变学理论，采用优化方法进行挤出成型模具（即机头）流道设计，探讨了建立流道优化数学模型的有关问题。     

辊压机水泥联台粉磨系统生产设计应注意的问题

山水集团新建粉磨站均采用辊压机和水泥磨组成的联合粉磨工艺，全部采用了国产化设备，且所建生产线均在短期内顺利实现了达标达产。文章概要介绍了该类粉磨生产线的主机配置及工艺流程；重点分析了为确保该类生产线的快速建成、高效益运行．在设计和生产管理中应该注意的相关问题和细节。