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排序方式: 共有384条查询结果,搜索用时 0 毫秒
41.
Goettert M Schattel V Koch P Merfort I Laufer S 《Chembiochem : a European journal of chemical biology》2010,11(18):2579-2588
A series of 42 naturally occurring flavonoids and one flavonoid glucuronide were tested for their ability to inhibit p38α mitogen-activated protein kinase (p38α) and c-Jun-N-terminal kinase 3 (JNK3). Potent inhibitors with IC(50) values in the low micromolar range were identified. Structure-activity relationships were evaluated and the most promising compounds were docked into the ATP binding site of these kinases. Among the different classes of flavonoids, the flavonol group showed better inhibition of p38α. Of this class, kaempferol-7,4'-dimethylether was a potent p38α inhibitor, displaying 13-fold selectivity for p38α over JNK3. The flavone compounds without a 6-methoxy group preferentially inhibited JNK3. The flavone glycoside, luteolin-7-O-glycoside, was identified as a potent inhibitor with the greatest selectivity toward JNK3. In contrast, the flavanol compounds displayed similar inhibitory activities toward both kinases. 相似文献
42.
Claudia Bracht Dominik R. J. Hauser Dr. Verena Schattel Wolfgang Albrecht Dr. Stefan A. Laufer Prof. Dr. 《ChemMedChem》2010,5(7):1134-1142
The p38 mitogen‐activated protein (MAP) kinase α plays a central role in the regulation of cellular responses such as differentiation, proliferation, apoptosis, and inflammation. Inhibition of p38 results in decreased synthesis of pro‐inflammatory cytokines. To date, diverse p38α inhibitors are in phase II clinical trials for numerous cytokine‐dependent diseases. 2‐Sulfanylimidazole derivatives offer advantages over the prototype inhibitor SB 203580, including fewer cytochrome P450 interactions and better kinetic properties. The aim of this study was to develop novel 1,2,4,5‐tetrasubstituted pyridinylimidazoles with acyl residues at the imidazole N1 position that can interact with the kinase's hydrophobic region II (HR II) or sugar pocket (SP) to improve both selectivity and activity. The substitution pattern was optimized by variation of the acyl moiety at the N1 position of the N‐aminoimidazole core. Acylation of the amino function was used for optimization and led to potent p38α MAPK inhibitors. 相似文献
43.
Verena Preis Sebastian Hahnel Carola Kolbeck Detlef Behrend Mareike Warkentin Gerhard Handel Martin Rosentritt 《Advanced Engineering Materials》2011,13(12):B432-B439
The aim of this in vitro study was to compare the two‐body wear resistance of different dental ceramics and non‐precious alloys. Two‐body wear tests were performed in a chewing simulator with steatite antagonists. A pin‐on‐block design with a vertical load of 50 N for 1.2 × 105 cycles (f = 1.6 Hz; lateral movement: 1 mm, mouth opening: 2 mm) was used for the wear test. Surface roughness Ra (SP6, Perthen‐Feinprüf, G) and wear depth were determined using a 3D‐Profilometer (Laserscan 3D, Willytec, G). Scanning electron microscopy (Quanta FEG 400, FEI, NL) was applied for evaluating wear performance of both, materials and antagonists. Statistics: one‐way ANOVA (α = 0.05). The in vitro wear test showed that the wear performance of dental materials is strongly influenced by the type of material (ceramic, zirconia, or alloy). Zirconia and alloy provided low wear in contrast to glass‐ceramic systems. In contradiction to common expectations, hard zirconia and alloy systems showed even lower antagonistic wear than glass‐ceramics. 相似文献
44.
Streaming media from the Internet is a successful application for end-users. With the upcoming success of mobile devices
and home networking environments, cooperation among users will become more important in the future. To achieve such cooperation,
explicit middleware standards have been defined. On the other hand, Internet conferencing applications do not handle collaborative
streaming sessions with individual control for each user. We propose a new concept for cooperation exemplary for collaborative
media streaming using IETF multimedia session control protocols together with a proxy architecture. This concept enables both
synchronization among clients and flexible control to individual users. 相似文献
45.
David Damm Christian Fremerey Verena Thomas Michael Clausen Frank Kurth Meinard Müller 《International Journal on Digital Libraries》2012,12(2-3):53-71
In this paper, we present a digital library system for managing heterogeneous music collections. The heterogeneity refers to various document types and formats as well as to different modalities, e. g., CD-audio recordings, scanned sheet music, and lyrics. The system offers a full-fledged, widely automated document processing chain: digitization, indexing, annotation, access, and presentation. Our system is implemented as a generic and modular music repository based on a service-oriented software architecture. As a particular strength of our approach, the various documents representing aspects of a piece of music are jointly considered in all stages of the document processing chain. Our user interfaces allow for a multimodal and synchronized presentation of documents (WYSIWYH: what you see is what you hear), a score- or lyrics-based navigation in audio, as well as a cross- and multimodal retrieval. Hence, our music repository may be called a truly cross-modal library system. In our paper, we describe the system components, outline the techniques of the document processing chain, and illustrate the implemented functionalities for user interaction. We describe how the system is put into practice at the Bavarian State Library (BSB) Munich as a part of the German PROBADO Digital Library Initiative (PDLI). 相似文献
46.
Verena B. K. Kunig Dr. Marco Potowski Dr. Mateja Klika Škopić Dr. Andreas Brunschweiger 《ChemMedChem》2021,16(7):1048-1062
Understanding the ligandability of a target protein, defined as the capability of a protein to bind drug-like compounds on any site, can give important stimuli to drug-development projects. For instance, inhibition of protein–protein interactions usually depends on the identification of protein surface binders. DNA-encoded chemical libraries (DELs) allow scanning of protein surfaces with large chemical space. Encoded library selection screens uncovered several protein–protein interaction inhibitors and compounds binding to the surface of G protein-coupled receptors (GPCRs) and kinases. The protein surface-binding chemotypes from DELs are predominantly chemically modified and cyclized peptides, and functional small-molecule peptidomimetics. Peptoid libraries and structural peptidomimetics have been less studied in the DEL field, hinting at hitherto less populated chemical space and suggesting alternative library designs. Roughly a third of bioactive molecules evolved from smaller, target-focused libraries. They showcase the potential of encoded libraries to identify more potent molecules from weak, for example, fragment-like, starting points. 相似文献
47.
Boris V. Sorokin Marina Pivetta Valerio Bellini Darius Merk Sébastien Reynaud Alessandro Barla Harald Brune Stefano Rusponi 《Advanced functional materials》2023,33(20):2213951
X-ray magnetic circular dichroism, atomic multiplet simulations, and density functional theory calculations are employed to identify criteria for the optimum combination of supporting alkaline earth oxide and adsorption site maximizing the spin lifetimes of lanthanide single-atom magnets. Dy and Ho atoms adsorbed on BaO(100) thin films on Pt(100) are characterized and compared with previous results for the same two elements on MgO/Ag(100). Dy shows hysteresis in magnetic fields up to ≈3.5 T and long spin lifetime, exceeding 300 s at 2.5 K and 0.5 T. Dy displays superior magnetic stability on the bridge site than on the top-O site. Surprisingly, Ho shows paramagnetism, as opposed to its long spin lifetime on MgO. These differences originate from the local surface distortions induced by the adatoms. On MgO, minimal distortions involve only the closest O atoms, while, on BaO, they affect both the closest anions and cations. This trend reflects the decrease of the lattice energy along the series of the alkaline earth oxides, going from MgO to BaO. This study represents a step ahead in the understanding of the factors determining the spin dynamics of surface-adsorbed single-atom magnets in order to achieve their operation as qubits and memories. 相似文献
48.
49.
Ulrich Koller Stefan Hainzl Thomas Kocher Clemens Hüttner Alfred Klausegger Christina Gruber Elisabeth Mayr Verena Wally Johann W. Bauer Eva M. Murauer 《International journal of molecular sciences》2015,16(1):1179-1191
Spliceosome-mediated RNA trans-splicing has become an emergent tool for the repair of mutated pre-mRNAs in the treatment of genetic diseases. RNA trans-splicing molecules (RTMs) are designed to induce a specific trans-splicing reaction via a binding domain for a respective target pre-mRNA region. A previously established reporter-based screening system allows us to analyze the impact of various factors on the RTM trans-splicing efficiency in vitro. Using this system, we are further able to investigate the potential of antisense RNAs (AS RNAs), presuming to improve the trans-splicing efficiency of a selected RTM, specific for intron 102 of COL7A1. Mutations in the COL7A1 gene underlie the dystrophic subtype of the skin blistering disease epidermolysis bullosa (DEB). We have shown that co-transfections of the RTM and a selected AS RNA, interfering with competitive splicing elements on a COL7A1-minigene (COL7A1-MG), lead to a significant increase of the RNA trans-splicing efficiency. Thereby, accurate trans-splicing between the RTM and the COL7A1-MG is represented by the restoration of full-length green fluorescent protein GFP on mRNA and protein level. This mechanism can be crucial for the improvement of an RTM-mediated correction, especially in cases where a high trans-splicing efficiency is required. 相似文献
50.
Depth distribution and mobility of a harpacticoid copepod within the bed sediment of an alpine brook
A. Verena Kowarc 《河流研究与利用》1992,7(1):57-63
The harpacticoid copepod Limnocamptus echinatus (Mrazek) shows a very distinct large-scale vertical distribution within the bed sediments of Oberer Seebach, a second-order gravel stream. The population peak appears in a sediment layer between 15 and 35 cm over long periods on average. Abundances are significantly lower in the topmost sediments and sediment layers below 50 cm depth. The large-scale vertical distribution is mainly influenced by the changes and pattern of temperature and discharge, which influences the current velocity of the surface and interstitial water. Effects appear quite different, when permanent flooded areas and areas that periodically fall dry on the surface are compared. Limnocamptus echinatus is forced deeper into the sediments of the gravel bar during low water temperatures and/or high discharge situations. On permanent flooded areas the vertical distribution is more stable over long periods, but higher fluctuations occur during short periods. The Limnocamptus echinatus population shows higher mobility in deeper sediment layers (40 to 60 cm sediment depth). Comparing longer periods, water flow and the transport of fine material differ in deeper sediment layers. The water current is much slower, producing a tendency for fine material sedimentation. This might be the main reason for the higher mobility in deeper sediment layers and the restriction of 90 per cent of the Limnocamptus echinatus population to a sediment depth of 50 cm. High mobility in vertical and horizontal directions within the bed sediments is interpreted as normal reactions and adaptations to the dynamic behaviour of the system, mainly forced by physical parameters. Biological parameters appear as subdominant for large-scale vertical distributions. 相似文献