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排序方式: 共有4795条查询结果,搜索用时 15 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.
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.
A Meneghetti WV Cardoso JS Brody MC Williams 《Canadian Metallurgical Quarterly》1996,44(10):1173-1182
Explants of embryonic lung are often used to characterize lung growth, bronchial tree pattern, and cell differentiation. Most investigators culture lungs for 3-7 days in defined media lacking, e.g., added growth factors or hormones. If growth and differentiation are comparable to that in vivo, these cultures show considerable promise for identifying developmental regulatory molecules and target genes, and for elucidating molecular responses. We used in situ hybridization and RT-PCR to compare times and sites of expression of mRNAs of six epithelial genes in cultured and uncultured fetal rat lungs. These genes, expressed in distal lung of adult rats, are surfactant proteins (SP) A, B, and C; LAR, a receptor-type tyrosine phosphatase; Clara cell secretory protein (CC10, CCSP); and T1alpha. SP-A, SF-B, LAR, and CC10 are expressed by both Clara and Type II cells in adult animals. SP-C and T1alpha are unique markers for Type II and Type I cells, respectively. SP-C, LAR, and T1alpha are expressed before the lung is explanted (Day 13.5); SP-A, -B, and CC10 mRNAs are first detected later. The onset of expression is similar in vivo and in vitro. Although the patterns of expression differ for each mRNA, their sites of expression in culture match those in vivo relative to the bronchial tree. The explanted embryonic lung appears to be an excellent experimental model. 相似文献
5.
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
6.
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
7.
Prostate enlargement in mice due to fetal exposure to low doses of estradiol or diethylstilbestrol and opposite effects at high doses 总被引:7,自引:0,他引:7
FS vom Saal BG Timms MM Montano P Palanza KA Thayer SC Nagel MD Dhar VK Ganjam S Parmigiani WV Welshons 《Canadian Metallurgical Quarterly》1997,94(5):2056-2061
On the basis of results of studies using high doses of estrogens, exposure to estrogen during fetal life is known to inhibit prostate development. However, it is recognized in endocrinology that low concentrations of a hormone can stimulate a tissue, while high concentrations can have the opposite effect. We report here that a 50% increase in free-serum estradiol in male mouse fetuses (released by a maternal Silastic estradiol implant) induced a 40% increase in the number of developing prostatic glands during fetal life; subsequently, in adulthood, the number of prostatic androgen receptors per cell was permanently increased by 2-fold, and the prostate was enlarged by 30% (due to hyperplasia) relative to untreated males. However, as the free serum estradiol concentration in male fetuses was increased from 2- to 8-fold, adult prostate weight decreased relative to males exposed to the 50% increase in estradiol. As a model for fetal exposure to man-made estrogens, pregnant mice were fed diethylstilbestrol (DES) from gestation days 11 to 17. Relative to controls, DES doses of 0.02, 0.2, and 2.0 ng per g of body weight per day increased adult prostate weight, whereas a 200-ng-per-g dose decreased adult prostate weight in male offspring. Our findings suggest that a small increase in estrogen may modulate the action of androgen in regulating prostate differentiation, resulting in a permanent increase in prostatic androgen receptors and prostate size. For both estradiol and DES, prostate weight first increased then decreased with dose, resulting in an inverted-U dose-response relationship. 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.
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
10.
Borman Walter C.; Hanson Mary Ann; Oppler Scott H.; Pulakos Elaine D.; White Leonard A. 《Canadian Metallurgical Quarterly》1993,78(3):443
Explores the role of early supervisory experience and cognitive ability in 1st-line supervisor performance. Similar to the F. L. Schmidt et al (see record 1986-31441-001) study of nonsupervisors, this research tested structural models hypothesizing relationships among supervisory experience, cognitive ability, supervisory knowledge and proficiency, and performance ratings, using a sample of 570 2nd-tour soldiers. The Schmidt et al model with an additional ability?→?experience path provided the best fit. The significant ability?→?experience path was interpreted as indicating that demonstrated ability contributes to soldiers being given the opportunity to obtain supervisory experience. Experience had a greater impact on supervisor proficiency than on supervisor knowledge. Ability had a greater impact on supervisor knowledge than on proficiency. Discussion focuses on the personal characteristics that might be involved in being assigned supervisory responsibilities. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献