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排序方式: 共有4526条查询结果,搜索用时 31 毫秒
891.
Dr. Dirk Kessler Dr. Moriz Mayer Dr. Stephan K. Zahn Dr. Markus Zeeb Dr. Simon Wöhrle Dr. Andreas Bergner Jens Bruchhaus Tuncay Ciftci Dr. Georg Dahmann Maike Dettling Sandra Döbel Dr. Julian E. Fuchs Dr. Leonhard Geist Wolfgang Hela Dr. Christiane Kofink Roland Kousek Franziska Moser Teresa Puchner Dr. Klaus Rumpel Maximilian Scharnweber Patrick Werni Bernhard Wolkerstorfer Dr. Dennis Breitsprecher Dr. Philipp Baaske Dr. Mark Pearson Dr. Darryl B. McConnell Dr. Jark Böttcher 《ChemMedChem》2021,16(9):1420-1424
Aberrant WNT pathway activation, leading to nuclear accumulation of β-catenin, is a key oncogenic driver event. Mutations in the tumor suppressor gene APC lead to impaired proteasomal degradation of β-catenin and subsequent nuclear translocation. Restoring cellular degradation of β-catenin represents a potential therapeutic strategy. Here, we report the fragment-based discovery of a small molecule binder to β-catenin, including the structural elucidation of the binding mode by X-ray crystallography. The difficulty in drugging β-catenin was confirmed as the primary screening campaigns identified only few and very weak hits. Iterative virtual and NMR screening techniques were required to discover a compound with sufficient potency to be able to obtain an X-ray co-crystal structure. The binding site is located between armadillo repeats two and three, adjacent to the BCL9 and TCF4 binding sites. Genetic studies show that it is unlikely to be useful for the development of protein–protein interaction inhibitors but structural information and established assays provide a solid basis for a prospective optimization towards β-catenin proteolysis targeting chimeras (PROTACs) as alternative modality. 相似文献
892.
Gia Quyet Ngo Antony George Robin Tristan Klaus Schock Alessandro Tuniz Emad Najafidehaghani Ziyang Gan Nils C. Geib Tobias Bucher Heiko Knopf Sina Saravi Christof Neumann Tilman Lühder Erik P. Schartner Stephen C. Warren-Smith Heike Ebendorff-Heidepriem Thomas Pertsch Markus A. Schmidt Andrey Turchanin Falk Eilenberger 《Advanced materials (Deerfield Beach, Fla.)》2020,32(47):2003826
Atomically thin transition metal dichalcogenides are highly promising for integrated optoelectronic and photonic systems due to their exciton-driven linear and nonlinear interactions with light. Integrating them into optical fibers yields novel opportunities in optical communication, remote sensing, and all-fiber optoelectronics. However, the scalable and reproducible deposition of high-quality monolayers on optical fibers is a challenge. Here, the chemical vapor deposition of monolayer MoS2 and WS2 crystals on the core of microstructured exposed-core optical fibers and their interaction with the fibers’ guided modes are reported. Two distinct application possibilities of 2D-functionalized waveguides to exemplify their potential are demonstrated. First, the excitonic 2D material photoluminescence is simultaneously excited and collected with the fiber modes, opening a novel route to remote sensing. Then it is shown that third-harmonic generation is modified by the highly localized nonlinear polarization of the monolayers, yielding a new avenue to tailor nonlinear optical processes in fibers. It is anticipated that the results may lead to significant advances in optical-fiber-based technologies. 相似文献
893.
Maria Karolin Streubel Johannes Bischof Richard Weiss Jutta Duschl Wolfgang Liedl Herbert Wimmer Michael Breitenbach Manuela Weber Florian Geltinger Klaus Richter Mark Rinnerthaler 《Yeast (Chichester, England)》2018,35(2):237-249
In recent decades Saccharomyces cerevisiae has proven to be one of the most valuable model organisms of aging research. Pathways such as autophagy or the effect of substances like resveratrol and spermidine that prolong the replicative as well as chronological lifespan of cells were described for the first time in S. cerevisiae. In this study we describe the establishment of an aging reporter that allows a reliable and relative quick screening of substances and genes that have an impact on the replicative lifespan. A cDNA library of the flatworm Dugesia tigrina that can be immortalized by beheading was screened using this aging reporter. Of all the flatworm genes, only one could be identified that significantly increased the replicative lifespan of S.cerevisiae. This gene is the cysteine protease cathepsin L that was sequenced for the first time in this study. We were able to show that this protease has the capability to degrade such proteins as the yeast Sup35 protein or the human α‐synuclein protein in yeast cells that are both capable of forming cytosolic toxic aggregates. The degradation of these proteins by cathepsin L prevents the formation of these unfolded protein aggregates and this seems to be responsible for the increase in replicative lifespan. 相似文献
894.
Shuai Liu Klaus Wippermann Werner Lehnert 《International Journal of Hydrogen Energy》2021,46(27):14687-14698
In this work, new insights into impacts of the polytetrafluoroethylene (PTFE) binder on high temperature polymer electrolyte fuel cells (HT-PEFCs) are provided by means of various characterizations and accelerated stress tests. Cathodes with PTFE contents from 0 wt% to 60 wt% were fabricated and compared using electrochemical measurements. The results indicate that the cell with 10 wt% PTFE in the cathode catalyst layer (CCL) shows the best performance due to having the lowest mass transport resistance and cathode protonic resistance. Moreover, cyclic voltammograms show that Pt (100) edge and corner sites are significantly covered by PTFE and phosphate anions when the PTFE content is higher than 25 wt%. Open-circuit and low load-cycling conditions are applied to accelerate degradation processes of the HT-PEFCs. The PTFE binder shows a network structure in the pores of the catalyst layer, which reduces phosphoric acid leaching during the aging tests. In addition, the high binder HT-PEFCs more easily suffer from a mass transport problem, leading to more severe performance degradation. 相似文献
895.
896.
Elena Putscher Michael Hecker Brit Fitzner Peter Lorenz Uwe Klaus Zettl 《International journal of molecular sciences》2021,22(10)
Splicing is an important RNA processing step. Genetic variations can alter the splicing process and thereby contribute to the development of various diseases. Alterations of the splicing pattern can be examined by gene expression analyses, by computational tools for predicting the effects of genetic variants on splicing, and by splicing reporter minigene assays for studying alternative splicing events under defined conditions. The minigene assay is based on transient transfection of cells with a vector containing a genomic region of interest cloned between two constitutive exons. Cloning can be accomplished by the use of restriction enzymes or by site-specific recombination using Gateway cloning. The vectors pDESTsplice and pSpliceExpress represent two minigene systems based on Gateway cloning, which are available through the Addgene plasmid repository. In this review, we describe the features of these two splicing reporter minigene systems. Moreover, we provide an overview of studies in which determinants of alternative splicing were investigated by using pDESTsplice or pSpliceExpress. The studies were reviewed with regard to the investigated splicing regulatory events and the experimental strategy to construct and perform a splicing reporter minigene assay. We further elaborate on how analyses on the regulation of RNA splicing offer promising prospects for gaining important insights into disease mechanisms. 相似文献
897.
Butler Michael Hoang Thai Son Raschke Alexander Reichl Klaus 《International Journal on Software Tools for Technology Transfer (STTT)》2020,22(3):249-255
International Journal on Software Tools for Technology Transfer - This paper introduces the topic of the Special Section on the ERTMS Level 3 Hybrid case study. The European Rail Traffic Management... 相似文献
898.
Yazhou Zhou Guangbo Chen Qing Wang Ding Wang Xiafang Tao Tierui Zhang Xinliang Feng Klaus Müllen 《Advanced functional materials》2021,31(34):2102420
The development of iron and nitrogen co-doped carbon (Fe N C) electrocatalysts for the oxygen reduction reaction (ORR) in proton-exchange membrane fuel cells (PEMFCs) is a grand challenge due to the low density of accessible Fe N4 sites. Here, an in situ trapping strategy using nitrogen-rich molecules (e.g., melamine, MA) is demonstrated to enhance the amount of accessible Fe N4 sites in Fe N C electrocatalysts. The melamine molecules can participate in the coordination of Fe ions in zeolitic imidazolate frameworks to form Fe N6 sites within precursors. These Fe N6 sites are then converted into atomically dispersed Fe N4 sites during a pyrolytic process. Remarkably, the Fe N C/MA exhibits a high single-atom Fe content (3.5 wt.%), a large surface area (1160 m2 g−1), and a high density of accessible FeN4 sites (45.7 × 1019 sites g−1). As a result, Fe N C/MA shows a much enhanced ORR activity with a half-wave potential of 0.83 V (vs the reversible hydrogen electrode) in a 0.5 m H2SO4 electrolyte solution and a good performance in a PEMFC system with an activity of 80 mA cm−2 at 0.8 V under 1.0 bar H2/air. This work offers a promising approach toward high-performance carbon-based ORR electrocatalysts. 相似文献
899.
S. Palantöken K. Bethke V. Zivanovic G. Kalinka Janina Kneipp Klaus Rademann 《应用聚合物科学杂志》2020,137(7):48380
Biopolymers are very efficient for significant applications ranging from tissue engineering, biological devices to water purification. There is a tremendous potential value of cellulose because of its being the most abundant biopolymer on earth, swellability, and functional groups to be modified. A novel, highly efficient route for the fabrication of mechanically stable and natural hydrogels is described in which cellulose and glycine are dissolved in an alkaline solution of NaOH and neutralized in an acidic solution. The dissolving temperature and the glycine amount are essential parameters for the self-assembly of cellulose chains and for tuning the morphology and the aggregate structures of the resulting hydrogels. Glycine plays the role of a physical crosslinker based on the information obtained from FTIR and Raman spectra. Among the prepared set of hydrogels, CL5Gly30 hydrogels have the highest capacity to absorb water. The prepared CL5Gly30 gels can absorb up to seven times their dry weight due to its porous 3-D network structure. CL5Gly10 hydrogel exhibits 80% deformation under 21 N force executed. The method developed in this article can contribute to the application of heavy metal adsorption in aqueous solutions for water purification and waste management. © 2019 The Authors. 137 published by Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2020 , 137, 48380. 相似文献