Tetrahydroindoles as Multipurpose Screening Compounds and Novel Sirtuin Inhibitors

Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp³ hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC₅₀ value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling.     

Experimental and numerical analysis of the influence of cable tray arrangements on the resulting mass loss rate and fire spreading

In the context of industrial buildings and power plants, electrical installations and cable trays represent a main fuel load and a potential initial fire source due to possible short circuits or comparable malfunction. Furthermore, a fire can spread from one tray to additional trays mounted above and/or horizontally on one tray. Because of the high significance of cable fires, several research projects have been carried out, investigating the fire behaviour of cables from small‐scale tests, eg, the cone calorimeter, up to large‐scale tests, analysing complete cable tray constructions. The goal of the work presented in this paper is the extension of the knowledge regarding the influence of geometrical parameters like the packing density and tray distance on the burning behaviour and fire spread of cable tray installations. The results are considered, together with test results from the literature, to quantify the main physical parameters describing the burning behaviour. In a next step, the general applicability of these parameters as input data for the parametrization of the source term of numerical simulations is shown. The test results show that the burning behaviour and the fire spreading highly depend on the cable arrangement of the cables on the cable tray, in combination with other boundary conditions. By applying the results as input for a fire simulation, the mass loss rate is considered appropriately.     

Dielectric relaxation of vegetable-based polyurethane

Vegetable-based polyurethane (PU) was prepared in the thin film form by spin coating. This polymer is synthesised from castor oil, which can be extracted from the seeds of a native plant in Brazil called mamona. This polymer is biocompatible and is being used as material for artificial bone. The PU was characterised by dielectric spectroscopy in a wide range of frequency (10^–5 Hz to 10⁵ Hz) and by thermally stimulated discharge current (TSDC) measurements. The glass transition temperature (T _g = 39°C) was determined and using the initial rise method the activation energy was found to be 1.58 eV.     

浅谈东深供水改造工程的设计监理工作

施工图阶段设计监理工作的内容归纳起来主要是对设计质量进行控制.依据<水利建设工程招标、施工图阶段设计监理试行规定>,其具体工作内容仅限于设计成果的合法性和安全性,没有充分发挥设计监理作用,对施工图阶段设计质量的理解是不全面的.施工图阶段的设计质量不仅仅是提交合法和安全的图纸,而且图纸的提交时限性、可实施性及经济性也应是考核设计质量的重要组成部分,为此东深供水改造工程的设计监理工作内容确定为"五项控制"和"两项权利",全面地对施工图阶段的设计质量进行控制.     

大坝监测自动化中的人工比测研究

阐述了人工比测的概念、方式和数据分析方法,对人工比测及数据分析中应注意的问题也进行了深入研究。     

MODELING OF WATER DYNAMICS AND POLLUTANT SPREADING IN THE LUOMAHU RESERVOIR FOR WATER TRANSFER FORM SOUTH TO NORTH OF CHINA

1 .　ＩＮＴＲＯＤＵＣＴＩＯＮＷａｔｅｒＴｒａｎｓｆｅｒＦｒｏｍＳｏｕｔｈＴｏＮｏｒｔｈＰｒｏｊｅｃｔ(ＷＴＦＳＴＮＰ)ｉｓａｇｒｅａｔｄｅｃｉｓｉｏｎｔｏｓｏｌｖｅｔｈｅｐｒｏｂｌｅｍｏｆｗａｔｅｒｓｈｏｒｔａｇｅｉｎｔｈｅｎｏｒｔｈａｎｄｃｅｎｔｒａｌｐａｒｔｓｏｆＣｈｉ ｎａ .Ｔｈｉｓｐｒｏｊｅｃｔ ,ｉｎｃｌｕｄｉｎｇＥａｓｔ ,Ｃｅｎｔｒａｌ ａｎｄＷｅｓｔ Ｌｉｎｅ ,ｗｉｌｌｄｒａｗｗａｔｅｒｆｒｏｍｔｈｅＹａｎｇｔｚｅＲｉｖｅｒｔｏｔｈｅｎｏｒｔｈａｎｄｃｅｎｔｅｒｏｆＣｈｉｎａｓｏｔｈａ…     

Engineering Geological Problems of Levee Along Middle and Lower Reaches of Yangtze River

1　ＩｎｔｒｏｄｕｃｔｉｏｎＢｅｃａｕｓｅｏｆｔｈｅｃｏｍｐｌｉｃａｔｅｄｓｕｂｓｏｉｌｐｒｏｆｉｌｅ ,ｔｈｅｌｅｖｅｅａｌｏｎｇｍｉｄｄｌｅａｎｄｌｏｗｅｒｒｅａｃｈｅｓｏｆＹａｎｇｔｚｅ ,ａｂｏｕｔ 36 0 0ｋｍｌｏｎｇ ,ｈａｓｍａｎｙｈｉｄｄｅｎｐｅｒｉｌｓ .Ａｍｏｎｇｔｈｅｄａｎｇｅｒｏｕｓｅｖｅｎｔｓｄｕｒｉｎｇ 1998’ｓｆｌｏｏｄｓｅａｓｏｎｉｎｔｈｅｗｈｏｌｅｖａｌｌｅｙ ,12 .7%ｏｃ ｃｕｒｒｅｄａｌｏｎｇｔｈｅｔｒｕｎｋｓｔｒｅａｍｄｙｋｅｓ,ｏｆｗｈｉｃｈ 6 98ｗｅｒｅｔｈｅｍｏｓｔｄ…     

吴岭水库土坝渗流及坝坡稳定性分析

本文对湖北省京山县吴岭水库土坝进行了有限元渗流计算和坝坡稳定性计算,在分析大坝基础部位的残坡积土、强风化砂岩的强透水性和下游排水体对于大坝渗流场的影响的基础上,得出渗流是引起下游坝坡不稳定的主要因素,为大坝的加固处理提供了理论依据,也可供同类土坝设计时参考。     

Clarification of a wheat straw‐derived medium with ion‐exchange resins for xylitol crystallization

BACKGROUND: Xylitol bioproduction from lignocellulosic residues comprises hydrolysis of the hemicellulose, detoxification of the hydrolysate, bioconversion of the xylose, and recovery of xylitol from the fermented hydrolysate. There are relatively few reports on xylitol recovery from fermented media. In the present study, ion‐exchange resins were used to clarify a fermented wheat straw hemicellulosic hydrolysate, which was then vacuum‐concentrated and submitted to cooling in the presence of ethanol for xylitol crystallization. RESULTS: Sequential adsorption into two anion‐exchange resins (A‐860S and A‐500PS) promoted considerable reductions in the content of soluble by‐products (up to 97.5%) and in medium coloration (99.5%). Vacuum concentration led to a dark‐colored viscous solution that inhibited xylitol crystallization. This inhibition could be overcome by mixing the concentrated medium with a commercial xylitol solution. Such a strategy led to xylitol crystals with up to 95.9% purity. The crystallization yield (43.5%) was close to that observed when using commercial xylitol solution (51.4%). CONCLUSION: The experimental data demonstrate the feasibility of using ion‐exchange resins followed by cooling in the presence of ethanol as a strategy to promote the fast recovery and purification of xylitol from hemicellulose‐derived fermentation media. Copyright © 2008 Society of Chemical Industry     

深化水管体制改革促进水务事业持续发展

普洱市位于云南省西南部，面积4．5万km^2，与越南、老挝、缅甸三国接壤，国境线长486km。新中国成立以来，历届党委、政府高度重视普洱市水利事业的发展，把除水害、兴水利作为造福人民、荫及子孙的百年大计。到2006年年底止，全市累计建成蓄引工程49163件，其中：蓄水工程637件（中型水库10座、小型水库262座、塘坝365座），设计库容47556万m^3：引水工程48526件，年供水总能力11亿m^3。[第一段]