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排序方式: 共有472条查询结果,搜索用时 125 毫秒
1.
Katja F. Hellendahl Felix Kaspar Dr. Xinrui Zhou Zhaoyi Yang Prof. Dr. Zhen Huang Prof. Dr. Peter Neubauer Dr. Anke Kurreck 《Chembiochem : a European journal of chemical biology》2021,22(11):2002-2009
Selenium-modified nucleosides are powerful tools to study the structure and function of nucleic acids and their protein interactions. The widespread application of 2-selenopyrimidine nucleosides is currently limited by low yields in established synthetic routes. Herein, we describe the optimization of the synthesis of 2-Se-uridine and 2-Se-thymidine derivatives by thermostable nucleoside phosphorylases in transglycosylation reactions using natural uridine or thymidine as sugar donors. Reactions were performed at 60 or 80 °C and at pH 9 under hypoxic conditions to improve the solubility and stability of the 2-Se-nucleobases in aqueous media. To optimize the conversion, the reaction equilibria in analytical transglycosylation reactions were studied. The equilibrium constants of phosphorolysis of the 2-Se-pyrimidines were between 5 and 10, and therefore differ by an order of magnitude from the equilibrium constants of any other known case. Hence, the thermodynamic properties of the target nucleosides are inherently unfavorable, and this complicates their synthesis significantly. A tenfold excess of sugar donor was needed to achieve 40−48 % conversion to the target nucleoside. Scale-up of the optimized conditions provided four Se-containing nucleosides in 6–40 % isolated yield, which compares favorably to established chemical routes. 相似文献
2.
R. Paxton Thedford Peter A. Beaucage Ethan M. Susca Corson A. Chao Katja C. Nowack Robert B. Van Dover Sol M. Gruner Ulrich Wiesner 《Advanced functional materials》2021,31(23):2100469
Mesoscale order can lead to emergent properties including phononic bandgaps or topologically protected states. Block copolymers offer a route to mesoscale periodic architectures, but their use as structure directing agents for metallic materials has not been fully realized. A versatile approach to mesostructured metals via bulk block copolymer self-assembly derived ceramic templates, is demonstrated. Molten indium is infiltrated into mesoporous, double gyroidal silicon nitride templates under high pressure to yield bulk, 3D periodic nanocomposites as free-standing monoliths which exhibit emergent quantum-scale phenomena. Vortices are artificially introduced when double gyroidal indium metal behaves as a type II superconductor, with evidence of strong pinning centers arrayed on the order of the double gyroid lattice size. Sample behavior is reproducible over months, showing high stability. High pressure infiltration of bulk block copolymer self-assembly based ceramic templates is an enabling tool for studying high-quality metals with previously inaccessible architectures, and paves the way for the emerging field of block-copolymer derived quantum metamaterials. 相似文献
3.
4.
Neil Gerard Quigley Dr. Stefano Tomassi Dr. Francesco Saverio di Leva Dr. Salvatore Di Maro Dr. Frauke Richter Dr. Katja Steiger Prof. Dr. Susanne Kossatz Prof. Dr. Luciana Marinelli Dr. Johannes Notni 《Chembiochem : a European journal of chemical biology》2020,21(19):2836-2843
αvβ6 Integrin is an epithelial transmembrane protein that recognizes latency-associated peptide (LAP) and primarily activates transforming growth factor beta (TGF-β). It is overexpressed in carcinomas (most notably, pancreatic) and other conditions associated with αvβ6 integrin-dependent TGF-β dysregulation, such as fibrosis. We have designed a trimeric Ga-68-labeled TRAP conjugate of the αvβ6-specific cyclic pentapeptide SDM17 (cyclo[RGD-Chg-E]-CONH2) to enhance αvβ6 integrin affinity as well as target-specific in-vivo uptake. Ga-68-TRAP(SDM17)3 showed a 28-fold higher αvβ6 affinity than the corresponding monomer Ga-68-NOTA-SDM17 (IC50 of 0.26 vs. 7.4 nM, respectively), a 13-fold higher IC50-based selectivity over the related integrin αvβ8 (factors of 662 vs. 49), and a threefold higher tumor uptake (2.1 vs. 0.66 %ID/g) in biodistribution experiments with H2009 tumor-bearing SCID mice. The remarkably high tumor/organ ratios (tumor-to-blood 11.2; -to-liver 8.7; -to-pancreas 29.7) enabled high-contrast tumor delineation in PET images. We conclude that Ga-68-TRAP(SDM17)3 holds promise for improved clinical PET diagnostics of carcinomas and fibrosis. 相似文献
5.
Johann Füller Katja Hutter Niclas Kröger 《International Journal of Project Management》2021,39(2):183-195
While crowdsourcing may strengthen a company's innovation performance, it is only rarely embedded in organizations as an innovation practice. Our action research shows that organizations often struggle with crowdsourcing projects as they represent a different form of innovation projects and require additional capabilities and skills e.g., to frame a crowd challenge, deal with IP rights, manage the crowd, or integrate the vast input into innovation projects. To overcome these problems, organizations have to invest in project-led learning to establish easy-to-use templates and routines e.g., to handle offered incentives or the applied winner selection processes. They further need to enable business-led learning as the established innovation structures, processes, and management practices do not cope with crowdsourcing projects and present some rigidities causing high coordination efforts. Organizations that are willing to run a number of consecutive crowdsourcing projects may rapidly improve their capabilities and even come up with scalable crowdsourcing services. Our findings further suggest that crowdsourcing, digital platforms, artificial intelligence, and as-a-service approaches may also add to general project capability building. 相似文献
6.
Anne Toppinen Miska Sauru Satu Pätäri Katja Lähtinen Anni Tuppura 《Construction Management & Economics》2019,37(4):201-216
In transitioning to a renewable material-based bio economy, growing public and industry interest is apparent for using wooden multistory construction (WMC) as a sustainable urban housing solution in Europe, but its business implications are not well understood. In our study, we evaluate, which internal and external factors of competitiveness are shaping the future of WMC, especially in the context of Finland and Sweden. Based on a multi-level perspective of socio-technical transitions, we conducted a three-stage dissensus-based Delphi study. The identified internal and external factors affecting the future competitiveness of the WMC business emphasize the importance of skilled architects and builders and the role of standardized building systems. Based on our results, the key aspects influencing the future competitiveness of WMC in the region are related to the development of technical infrastructure and project-based business networks, while additional changes in regulatory framework are perceived as less important. We conclude that towards 2030, the strong cognitive rules founded in the concrete-based building culture in these countries is likely to inhibit the dynamics of the socio-technical regime level. A change is also needed in the WMC business culture towards more open cross-sectoral collaboration and new business networks between different-sized players. 相似文献
7.
Characteristics of and selection criteria for support materials for cell immobilization in wastewater treatment 总被引:11,自引:0,他引:11
Emily J.T.M. Leenen Vítor A.P. Dos Santos Katja C.F. Grolle Johannes Tramper RenéH. Wijffels 《Water research》1996,30(12):2985-2996
For treatment of wastewater with immobilized cells, support materials need to meet the following criteria: insoluble, not biodegradable, high mechanical stability, high diffusivity, simple immobilization procedure, high biomass retention, minimal attachment of other organisms and preferably a low cost price. In order to compare which support materials are the most suitable, characteristics of several natural and synthetic materials have been determined. For this, both literature and experimental data were used. The immobilization procedures of natural gel materials, like alginate and carrageenan, are mild and cells grow well in these supports. Furthermore, the effective diffusion coefficients of substrates are close to those in water. These supports, however, appeared to be soluble, biodegradable and liable to abrasion. Synthetic gels, on the contrary, have better mechanical properties, but mostly lower substrate diffusion coefficients. Immobilization conditions are less mild resulting in low biomass retention. For application of entrapped nitrifying cells in wastewater-treatment systems synthetic gels, however, are promising. 相似文献
8.
Alexander Horcher Katja Tangermann-Gerk Walter Krenkel Michael Schmidt Rajendra K. Bordia Günter Motz 《International Journal of Applied Ceramic Technology》2022,19(2):856-865
Protective ceramic-based coatings are frequently the most suitable solutions for problems like corrosion and wear. It has been shown that the precursor technology is suitable for the preparation of ceramic coatings by pyrolysis in a furnace. However, the required high temperature for the preparation of the ceramic coatings limits this approach to high temperature-resistant substrates. A very innovative approach to overcome this restriction is the use of laser radiation as a thermal source for the pyrolysis of the preceramic polymer. In this paper, we report on a coating system, for steel substrates, consisting of a polysilazane (Durazane 2250) bond coat and a hard and dense top-coat composed of an organosilazane (Durazane 1800) with tetragonal ZrO2 particles and aluminum flakes as fillers pyrolyzed using Nd:YVO4 laser. The aluminum fillers led to a significant increase in absorption of the laser energy leading to the formation of a dense coating with a thickness up to 20 μm and a mainly cellular/columnar-dendritic microstructure. The microstructure, mechanical, and tribological behaviors of these composite coatings are reported and compared to those of laser pyrolyzed glass/ZrO2-filled polysilazane-based coatings reported in the literature. 相似文献
9.
Sylvia Chan Yannis Chan Giulia Foscari Alain Fouraux Alexander Giarlis Ekaterina Golovatyuk Inge Goudsmit Ravi Kamisetti Michael Kokora Barend Koolhaas Janice Kwok Katja Lam Michelle Lam Jedidiah Lau Miranda Lee Brigitta Lenz Brendan McGetrick Betty Ng Stephan Petermann Roberto Requejo Benny Tam 《城市环境设计》2014,(6):70-73
正OMA发展西九文化区,必须面对一项挑战:将一个盛载政府极大抱负,以及持分者多元利益的超大型多用途项目,转化成一个既有趣又严肃、既有规划又允许即兴、既中国化又国际化的文化区。这个文化区规模庞大,但不失亲密融洽的感觉;富地标性,但十分谦和;容易理解,却能带来惊喜。为避免造成过分冲击,OMA采纳了一种每个香港市民都熟悉的建筑类型作为方案的发展 相似文献
10.
Daniel Stubba Dr. Dennis Bensinger Janika Steinbacher Lilia Proskurjakov Álvaro Salcedo Gómez Dr. Uwe Schmidt Prof. Dr. Stefan Roth Prof. Dr. Katja Schmitz Prof. Dr. Boris Schmidt 《ChemMedChem》2019,14(23):2005-2022
The ubiquitin-proteasome system (UPS) is an established therapeutic target for approved drugs to treat selected hematologic malignancies. While drug discovery targeting the UPS focuses on irreversibly binding epoxyketones and slowly-reversibly binding boronates, optimization of novel covalent-reversibly binding warheads remains largely unattended. We previously reported α-ketoamides to be a promising reversible lead motif, yet the cytotoxic activity required further optimization. This work focuses on the lead optimization of phenoxy-substituted α-ketoamides combining the structure-activity relationships from the primed and the non-primed site of the proteasome β5 subunit. Our optimization strategy is accompanied by molecular modeling, suggesting occupation of P1′ by a 3-phenoxy group to increase β5 inhibition and cytotoxic activity in leukemia cell lines. Key compounds were further profiled for time-dependent inhibition of cellular substrate conversion. Furthermore, the α-ketoamide lead structure 27 does not affect escape response behavior in Danio rerio embryos, in contrast to bortezomib, which suggests increased target specificity. 相似文献