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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.
Matthias Siemon Olaf Riese Burkhard Forell Dominic Krnung Walter Klein‐Heßling 《火与材料》2019,43(5):497-513
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. 相似文献
3.
4.
Navab SinghAuthor Vitae Moitreyee Mukherjee-RoyAuthor VitaeSohan Singh MehtaAuthor Vitae 《Microelectronics Journal》2003,34(4):237-245
The patterning of contact holes by selecting out-of-focus image plane (defocus) using attenuated phase shift masks (APSM) has been studied. Defocus is found to enhance the image modulation at low partial coherence for contact holes with negative local average of mask function. Semi-dense holes up to 130 nm in 8% APSM have been printed by 0.5 μm defocus at a partial coherence of 0.31 using KrF scanner with highest numerical aperture of 0.68. However, these holes were closed with in-focus imaging. Defocus is also found to be beneficial for patterning the pitches that have extensive side lobes with in-focus imaging. 相似文献
5.
Walter K. Sakamoto Darcy H. F. Kanda Francisco de Assis Andrade D. K. Das-Gupta 《Journal of Materials Science》2003,38(7):1465-1470
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. 相似文献
6.
Adaptive motion control using neural network approximations 总被引:1,自引:0,他引:1
In this paper, we present a new adaptive technique for tracking control of mechanical systems in the presence of friction and periodic disturbances. Radial Basis Functions (RBFs) are used to compensate for the effects of nonlinearly occurring parameters in the friction and periodic disturbance model. Theoretical analysis, such as stability and transient performance, is provided. Furthermore, the performance of the adaptive RBF controller and its non-adaptive counterpart are compared. 相似文献
7.
Larissa Canilha Walter Carvalho Marco Giulietti Maria Das Graças Almeida Felipe João Batista Almeida E Silva 《Journal of chemical technology and biotechnology (Oxford, Oxfordshire : 1986)》2008,83(5):715-721
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 相似文献
8.
Cherng-Min MaAuthor Vitae 《Pattern recognition》2003,36(8):1775-1782
Generally, a reduction operation (e.g., thinning and shrinking) on 3D binary images can be represented as a set of reduction templates where every object voxel of the image satisfying any template is turned to a background voxel. Generally, it is rather difficult, error-prone and time-consuming for verifying the topological soundness of a 3D parallel reduction operation. This paper proposes sufficient conditions of time complexity O(n) for verifying the topological soundness of 3D parallel 6-subiteration reduction operations of n templates where such a kind of 3D reduction operations is performed alternatively from the six orthogonal directions to turn object voxels to background voxels. By such sufficient conditions, the topology soundness of a 3D 6-subiteration parallel reduction operation can be verified by checking each and every of its templates. 相似文献
9.
In this paper, we present a control methodology for a class of discrete time nonlinear systems that depend on a possibly exogenous scheduling variable. This class of systems consists of an interpolation of nonlinear dynamic equations in strict feedback form, and it may represent systems with a time-varying nonlinear structure. Moreover, this class of systems is able to represent some cases of gain scheduling control, Takagi-Sugeno fuzzy systems, as well as input-output realizations of nonlinear systems which are approximated via localized linearizations. We present two control theorems, one using what we call a “global” approach (akin to traditional backstepping), and a “local” approach, our main result, where backstepping is again used but the control law is an interpolation of local control terms. An aircraft wing rock regulation problem with varying angle of attack is used to illustrate and compare the two approaches. 相似文献
10.
Shawn Hu Author Vitae Author Vitae 《Automatica》2007,43(7):1243-1248
This paper is concerned with stability analysis of discrete-time networked control systems over a communication channel subject to packet loss whose behavior is modeled by an i.i.d Bernoulli process with a packet dropping probability bounded by a constant. A necessary and sufficient condition for stability is obtained. A packet dropping margin is introduced as a measure of stability robustness of a system against packet dropping, and a formula for it is derived. A design method is proposed for achieving a large margin subject to a constraint that the system has a set of prescribed nominal closed-loop poles. 相似文献