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排序方式: 共有754条查询结果,搜索用时 31 毫秒
1.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
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. 相似文献
2.
Daniel Whittaker Andreas Geist Giuseppe Modolo Robin Taylor Mark Sarsfield Andreas Wilden 《溶剂提取与离子交换》2018,36(3):223-256
Over the last decade there has been much interest in the applications of diglycolamide (DGA) ligands for the extraction of the trivalent lanthanide and actinide ions from PUREX high active raffinates or dissolved spent nuclear fuel. Of the DGAs, the N,N,N’,N’-tetraoctyldiglycolamide (TODGA) is the best known and most widely studied. A number of new actinide separation processes have been proposed based on extraction with TODGA. This review covers TODGA-based processes and extraction data, specifically focusing on how phase modifiers have been used to increase metal loading and thus enhance the operating process envelopes. Effects of third phase formation and the organic phase speciation are reviewed in this context. Relevant aspects of the extraction chemistry of important solvents (TODGA-modifier-diluent combinations) are described and their performances demonstrated by a consideration of the published flowsheet tests. It is seen that modifiers are successfully enabling the use of TODGA in actinide separation processes but to date the identification and testing of suitable modifiers has been rather empirical. There is a growing understanding of the fundamental chemistry occurring in the organic phase and how that affects extractant speciation and metal loading capacity but studies are still needed if TODGA-based flowsheets are to become an industrially deployable option for minor actinide (MA) recovery processes. 相似文献
3.
Separation tests using hollow-fibre modules were performed for the difficult selective extraction of trivalent actinides over fission lanthanides from acidic media. This article shows that with 2,6-di(5,6-dipropyl-1,2,4-triazin-3-yl)pyridine as the extractant, up to 94% americium could be extracted from 1.0 kmol/m3 HNO3, with minimal lanthanide co-extraction. Using a synergistic mixture of bis(chlorophenyl)dithiophosphinic acid and tri-n-octyl phosphine oxide, tests were performed on extraction, lanthanide scrubbing and stripping. In the extraction test, up to 99.99% americium could be extracted from 0.5 kmol/m3 HNO3, with approximately one third of the lanthanides being co-extracted. Mass transfer calculations using a consistent set of input data showed good agreement with the experiments. 相似文献
4.
5.
This article addresses the results of the recent North and Fairchild article on observer metamerism. It reports on the results of a different experiment that produced similar results to those of North and Fairchild. The history of observer metamerism is outlined briefly and some possible sources of the large variations in inter-observer matches are suggested. Finally, a plea for a commercially viable special index of metamerism for change in observer is formulated. © 1995 John Wiley & Sons, Inc. 相似文献
6.
Numerical Modeling of Silicon Photodiodes for High-Accuracy Applications Part I. Simulation Programs
Jon Geist Deane Chandler-Horowitz A. M. Robinson C. R. James 《Journal of research of the National Institute of Standards and Technology》1991,96(4):463-469
The suitability of the semiconductor-device modeling program PC-1D for high-accuracy simulation of silicon photodiodes is discussed. A set of user interface programs optimized to support high-accuracy batch-mode operation of PC-1D for modeling the internal quantum efficiency of photodiodes is also described. The optimization includes correction for the dark current under reverse- and forward-bias conditions before calculating the quantum efficiency, and easy access to the highest numerical accuracy available from PC-1D, neither of which is conveniently available with PC-1D’s standard user interface. 相似文献
7.
We study the problem of parallel computation of a schedule for a system of n unit-length tasks on m identical machines, when the tasks are related by a set of precedence constraints. We present NC algorithms for computing an optimal schedule in the case where m, the number of available machines, does not vary with time and the precedence constraints are represented by a collection of outtrees. The algorithms run on an exclusive read, exclusive write (EREW) PRAM. Their complexities are O(log n) and O((log n)2) parallel time using O(n2) and O(n) processors, respectively. The schedule computed by our algorithms is a height-priority schedule. As a complementary result we show that it is very unlikely that computing such a schedule is in NC when any of the above conditions is significantly relaxed. We prove that the problem is P-complete under logspace reductions when the precedence constraints are a collection of intrees and outtrees, or for a collection of outtrees when the number of available machines is allowed to increase with time. The time span of a height-priority schedule for an arbitrary precedence constraints graph is at most 2 − 1/(m − 1) times longer than the optimal (N. E Chen and C. L. Liu, Proc. 1974 Sagamore Computer Conference on Parallel Processing, T. Fend (Ed.), Springer-Verlag, Berlin, 1975, pp. 1–16). Whereas it is P-complete to produce the classical height-priority schedules even for very restricted precedence constraints graphs, we present a simple NC parallel algorithm which produces a different schedule that is only 2 − 1/m times the optimal. 相似文献
8.
The increasing use of microelectrodes in small sample volumes and biological environments require the use of thin film insulators. The insulating ability of the thin film insulators electrophoretic paint, polyimide, allylphenol phenol copolymer and an epoxy dip coat have been assessed using gold wires coated in the relevant film. Insulation was assessed by recording the current from the wires in a solution of known redox couple. The effect of prolonged storage in aqueous solutions was also investigated. The most successful insulating approach, with regards to insulative ability, prolonged use in aqueous environments and speed of application, was the combination of cathodic electrophoretic paint followed by polyimide. 相似文献
9.
Environment as a first class abstraction in multiagent systems 总被引:2,自引:1,他引:1
The current practice in multiagent systems typically associates the environment with resources that are external to agents and their communication infrastructure. Advanced uses of the environment include infrastructures for indirect coordination, such as digital pheromones, or support for governed interaction in electronic institutions. Yet, in general, the notion of environment is not well defined. Functionalities of the environment are often dealt with implicitly or in an ad hoc manner. This is not only poor engineering practice, it also hinders engineers to exploit the full potential of the environment in multiagent systems. In this paper, we put forward the environment as an explicit part of multiagent systems.We give a definition stating that the environment in a multiagent system is a first-class abstraction with dual roles: (1) the environment provides the surrounding conditions for agents to exist, which implies that the environment is an essential part of every multiagent system, and (2) the environment provides an exploitable design abstraction for building multiagent system applications. We discuss the responsibilities of such an environment in multiagent systems and we present a reference model for the environment that can serve as a basis for environment engineering. To illustrate the power of the environment as a design abstraction, we show how the environment is successfully exploited in a real world application. Considering the environment as a first-class abstraction in multiagent systems opens up new horizons for research and development in multiagent systems. 相似文献
10.
Visual comfort and electric lighting energy issues are essential criteria to justify daylighting schemes. The evaluation of energy efficiency due to daylight linked lighting control systems is best demonstrated by case studies. This paper presents field measurements on daylighting for a fully air-conditioned daylit corridor. Artificial lighting load, brightness of the fluorescent luminaires, daylight availability for various switching illuminance levels were systematically recorded and analyzed. The general features and characteristics of the findings including the number of switching operations and electric-lighting energy savings are presented and discussed. Daylighting theories, using cumulative frequency distribution of outdoor illuminance and regression models based on brightness of light output, outdoor illuminance and electric light power to estimate daylight-linked lighting control savings, have been developed and assessed. It has been found that data from both approaches show reasonably good agreements with measured results. The findings from this study provide some operational and energy information, which would be useful and applicable to other interior spaces with similar architectural designs. 相似文献