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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.
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
4.
5.
Temperature control offers benefits in land‐based marine aquaculture: stock growth rates may be enhanced by heating in winter; mortality rates in summer may be reduced by cooling. However, if the plant is not well designed, temperature control may create very large energy demands. This paper describes the application of temperature control in abalone aquaculture in New Zealand, with a focus on energy considerations in plant design. An abalone farm using a semi‐closed water conditioning system is used as a case study for which an energy model, based on a heat pump system, is developed. The model is used to determine the impact of plant design and tank conditions on the economics of the operation. Copyright © 2002 John Wiley & Sons, Ltd. 相似文献
6.
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
7.
Hans-Dirk Walter 《Informatik-Spektrum》2008,31(4):333-343
Zusammenfassung ,,Rich Internet Applications“ (RIA) sind Webapplikationen, die mit einer wesentlich interaktiveren Benutzerschnittstelle ausgestattet
sind, als wir das bisher von den auf HTML basierten ,,poor ugly web applications“ (PUWA) gewohnt waren. 相似文献
8.
Prof. Dipl.-Ing. Dr.techn. Walter Gretler Prof. Dr. Si-min Zeng 《Forschung im Ingenieurwesen》1996,62(5):105-115
A numerical simulation of unsteady compressible flow induced by two high-speed trains in oncoming traffic within a tunnel
is presented. The computations were carried out by means of a second-order accurate Harten-Yee type upwind TVD scheme. In
order to take the effect of friction into account, a source term is included in the governing flow equations. In the computation,
moving boundary configurations were used to simulate the two trains passing through the tunnel. As geometrical configuration,
the Einmalberg tunnel, where experimental data are available, was selected. The computational results agree reasonably well
with their experimental counter-part. The waves interaction and the waves propagation process at the tunnel entrance and exit
as well as within the tunnel are addressed. Finally, the influence on the transmitted waves at the tunnel exit portal and
the variation of the negative pressure drop during the passage of the two trains are discussed. 相似文献
9.
SJ Hicks SD Carrington RL Kaswan S Adam J Bara AP Corfield 《Canadian Metallurgical Quarterly》1997,64(4):597-607
Our aims were to separate and characterize secreted canine ocular mucins, and to provide definitive evidence of membrane-bound mucins at the canine ocular surface. Mucus was collected by suction from the ocular surface of normal dogs and dispersed in guanidine hydrochloride and a cocktail of protease inhibitors. Caesium chloride density gradient centrifugation separated secreted mucins from membranes, which were collected from the top of the gradients. Membranes were extracted with octyl glucoside and screened using lectins and anti-mucin antibodies. Gradient fractions containing secreted mucins were constituted into pools on the basis of differential lectin and antibody staining. High molecular weight material from each pool was purified by gel filtration. This material, and the membrane extract, were reduced and alkylated. Vacuum blotting of separated materials after agarose gel electrophoresis was used to compare subunit structure. Density gradient profiles indicated three principal secreted glycoprotein peaks: one staining strongly with anti-mucin antibodies. Gel filtration demonstrated that each contained high molecular weight material. Vacuum blots demonstrated the presence of two secreted glycoproteins with differently sized subunits. On the basis of buoyant density, one of these may be lipid complexed. Membrane extracted material stained with anti-mucin antibodies, and vacuum blotting of this material provided evidence for two membrane-bound components. In conclusion, we have shown that normal canine ocular mucus contains two secreted mucins, each exhibiting different subunit structure; one of these mucins may undergo lipid complexation. Normal canine ocular mucus also contains two membrane-bound mucins: one of which is unique among membrane mucins in showing subunit structure. 相似文献
10.
Systemised serendipity for producing computer art 总被引:4,自引:0,他引:4
David Walter 《Computers & Graphics》1993,17(6):699-700
Serendipity applied to Newton's method, and its derivative the Secant Method, produces unusual and beautiful fractal patterns. Serendipity may be systemised, for example, by the introduction of a perturbation parameter P1, [1] to facilitate searches for interesting pattern variations. 相似文献