Potent inhibitors of the human UDP-glucuronosyltransferase 2B7 derived from the sesquiterpenoid alcohol longifolol

The tricyclic sesquiterpenol (+)-longifolol served as a lead structure for the design of inhibitors of the human UDP-glucuronosyltransferase (UGT) 2B7. Twenty-four homochiral and epimeric longifolol derivatives were synthesized and screened for their ability to inhibit the enzyme. The absolute configuration at the stereogenic center C1' was determined by X-ray crystallography and 2D NMR spectroscopy (gHSQC, gNOESY). The phenyl-substituted secondary alcohol 16 b (beta-phenyllongifolol) displayed the highest affinity toward UGT2B7, and its inhibitory dissociation constant was 0.91 nM. The mode of inhibition was rapidly reversible and competitive. The inhibitor was not glucuronidated by UGT2B7 or other hepatic UGTs, presumably as a result of the high steric demand exerted by the phenyl group. Inhibition assays employing 14 other UGT isoforms suggested that inhibitor 16 b was highly selective for UGT2B7.     

The Integration of Vacuum Brazing into Heat Treatment - A Progressive Combined Process

The continuous constructive challenge to improve the functionality and efficiency of components always results in higher demands on production engineering, against the background of the generally increasing cost pressure. In many cases, you will just succeed in producing competitive and innovative products by combining and coupling of different procedures to an independent (hybrid) technology. The use of hybrid procedures for metal joining and heat treatment of metallic materials finds more and more industrial fields of application. Modern vacuum lines with integrated pressurized gas quenching are considered high-performance and flexible means of production for brazing and heat treatment tasks as well in the turbine industry as in the mould making and tool manufacturing industry. In doing so, the heat treatment is coupled with the brazing cycle in a combined process so that the brazing temperatures and soak times are adapted to the necessary temperatures and times for solution heat treatment and austeniting. This user-oriented article describes on the one hand examples of brazing of turbine components, but above all the practical experience from the plastics processing industry, where the requirement for a high-efficient cooling of injection moulding dies gains more and more importance.The combined procedure “Vacuum Brazing and Hardening” offers plenty of possibilities to produce mould inserts with an efficient tempering system in an economic way.     

Pooled versus separate measurements of tree-ring stable isotopes

δ¹³C and δ¹⁸O of tree rings contain time integrated information about the environmental conditions weighted by seasonal growth dynamics and are well established as sources of palaeoclimatic and ecophysiological data. Annually resolved isotope chronologies are frequently produced by pooling dated growth rings from several trees prior to the isotopic analyses. This procedure has the advantage of saving time and resources, but precludes from defining the isotopic error or statistical uncertainty related to the inter-tree variability. Up to now only a few studies have compared isotope series from pooled tree rings with isotopic measurements from individual trees. We tested whether or not the δ¹³C and the δ¹⁸O chronologies derived from pooled and from individual tree rings display significant differences at two locations from the Iberian Peninsula to assess advantages and constraints of both methodologies. The comparisons along the period 1900-2003 reveal a good agreement between pooled chronologies and the two mean master series which were created by averaging raw individual values (Mean) or by generating a mass calibrated mean (MassC). In most of the cases, pooled chronologies show high synchronicity with averaged individual samples at interannual scale but some differences also show up especially when comparing δ¹⁸O decadal to multi-decadal variations. Moreover, differences in the first order autocorrelation among individuals may be obscured by pooling strategies. The lack of replication of pooled chronologies prevents detection of a bias due to a higher mass contribution of one sample but uncertainties associated with the analytical process itself, as sample inhomogeneity, seems to account for the observed differences.     

Coarsening Investigations of Precipitates in PM Tool Steel Grades: an Effect of Nitrogen

We present experimental and theoretical comparisons of the coarsening rate for the MX (X?=?C, N or C?+?N) precipitate in five different tool steel grades produced by Powder Metallurgy (PM). The alloys contain different amounts of nitrogen and carbon; ranging from high carbon/low nitrogen to high nitrogen/low carbon. Common for the grades is a high amount of precipitate forming alloying elements resulting in a high fraction of hard phase. Experimentally we have found out that the nitrogen rich precipitates coarsen slower, both for higher and lower carbon content, than the carbon rich precipitates. Coarsening simulations are performed utilizing the DICTRA software and an agreement between calculations and measurements can be concluded.     

Eine Stellungnahme zum Beitrag von Sass & Treskatis: “Herstellungs- und Bemessungsgrundlagen für einen verlaufsgesteuerten Trinkwasserbrunnen ...”

Ohne Zusammenfassung Eingang des Beitrages: 14.03.2000 / Eingang des überarbeiteten Beitrages: nicht überarbeitet, nur korrigiert     

Verlaufsgesteuerte Trinkwasserbrunnen als neues Fassungsorgan für die Grundwassererschließung

Curved horizontal wells have been developed in the late nineties for the purpose of in situ remediation of contaminated water. The discharge of contaminated backwater has been performed very successfully. These wells are usually designed for short time use with high precision and lower requirements on productivity in comparison to the needs of fresh water discharge from groundwater. Potable water resources are explored with highly productive and durable water wells. Classical wells are vertical and radial collector wells. Under certain hydrogeological conditions a curved horizontal well may be more efficient than classical wells. Therefore well construction and design have been accepted to meet the requirements of fresh water exploration. This paper compares the three fundamental well design principles. A quantitative analytical engineering concept is presented on a basis of the Dupuit-Thiem well equation. Especially the geometry of draw-down figures is reflected in this calculations.     

适度硬化表面淬火钢的加工和应用(一)

表面淬火钢的硬化程度对变速器零件的加工和应用起到决定性的作用.硬化程度主要取决于材料的化学成分,是选择表面淬火钢淬火温度的主要标准,因为稳定的材料质量是高效率大规模生产的保证.顶端淬火样品的变形和热处理条件对测量结果具有决定性的影响.由于明显的不确定性,必须考虑到顶端淬火试验测定的硬化程度和材料化学成分之间的不同.在狭窄的硬化程度范围内对表面淬火钢的热处理确保了可预测和可再现的大规模生产.一些实例表明,由于稍稍偏离所需的硬化程度范围造成不规则的热处理变形,并因成本问题而被放弃.     

Reconstruction of limited computed tomography data of fuel cell components using Direct Iterative Reconstruction of Computed Tomography Trajectories

CT (computed tomography) reconstructions of fuel cell components of a yet unrivaled spatial resolution and quality are presented. This is achieved by application of the novel DIRECTT (Direct Iterative Reconstruction of Computed Tomography Trajectories) algorithm. We focus on two different key issues which essentially rule the fuel cell's durability on different length scales and physical interactions. On the resolution scale of some 100 μm agglomerations of condensed water in flow-field channels are detected by means of quasi-in situ neutron CT (after operation). Five orders of magnitude below nanometer sized Ru catalyst particles on carbon black support are visualized by electron tomography. Both types of experiments are especially adapted to the type of material involved but they are accompanied by severe deviations from ideal CT measuring conditions, as well. In order to overcome the tremendous reconstruction artifacts of standard algorithms, we employ DIRECTT which is described in detail. Comparisons of DIRECTT reconstructions to the conventional filtered back projection, prove the significant improvements in both experimental methods.