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Dr. Armin Welker Dr. Christian Kersten Dr. Christin Müller Dr. Ramakanth Madhugiri Collin Zimmer Patrick Müller Robert Zimmermann Stefan Hammerschmidt Hannah Maus Prof. John Ziebuhr Prof. Christoph Sotriffer Prof. Tanja Schirmeister 《ChemMedChem》2021,16(2):340-354
Inhibition of coronavirus (CoV)-encoded papain-like cysteine proteases (PLpro) represents an attractive strategy to treat infections by these important human pathogens. Herein we report on structure-activity relationships (SAR) of the noncovalent active-site directed inhibitor (R)-5-amino-2-methyl-N-(1-(naphthalen-1-yl)ethyl) benzamide ( 2 b ), which is known to bind into the S3 and S4 pockets of the SARS-CoV PLpro. Moreover, we report the discovery of isoindolines as a new class of potent PLpro inhibitors. The studies also provide a deeper understanding of the binding modes of this inhibitor class. Importantly, the inhibitors were also confirmed to inhibit SARS-CoV-2 replication in cell culture suggesting that, due to the high structural similarities of the target proteases, inhibitors identified against SARS-CoV PLpro are valuable starting points for the development of new pan-coronaviral inhibitors. 相似文献
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Kersten Alan W.; Meissner Christian A.; Lechuga Julia; Schwartz Bennett L.; Albrechtsen Justin S.; Iglesias Adam 《Canadian Metallurgical Quarterly》2010,139(4):638
Three experiments provide evidence that the conceptualization of moving objects and events is influenced by one's native language, consistent with linguistic relativity theory. Monolingual English speakers and bilingual Spanish/English speakers tested in an English-speaking context performed better than monolingual Spanish speakers and bilingual Spanish/English speakers tested in a Spanish-speaking context at sorting novel, animated objects and events into categories on the basis of manner of motion, an attribute that is prominently marked in English but not in Spanish. In contrast, English and Spanish speakers performed similarly at classifying on the basis of path, an attribute that is prominently marked in both languages. Similar results were obtained regardless of whether categories were labeled by novel words or numbered, suggesting that an English-speaking tendency to focus on manner of motion is a general phenomenon and not limited to word learning. Effects of age of acquisition of English were also observed on the performance of bilinguals, with early bilinguals performing similarly in the 2 language contexts and later bilinguals showing greater contextual variation. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献
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Peter Mysling Kersten Petersen Mads Nielsen Martin Lillholm 《Machine Vision and Applications》2013,24(7):1421-1434
Segmentation of vertebral contours is an essential task in the design of imaging biomarkers for osteoporosis based on vertebra shape or texture. In this paper, we propose a novel automatic segmentation technique which can optionally be constrained by the user. The proposed technique solves the segmentation problem in a hierarchical manner. In the first phase, a coarse estimate of the overall spine alignment and the vertebra locations is computed using a sampling scheme. These samples are used to initialize a second phase of active shape model search, under a nonlinear model of vertebra appearance. The search is constrained by a conditional shape model, based on the variability of the coarse spine location estimates. In supplement, we describe an approach for manual initialization of the segmentation procedure as a simple set of constraints on the fully automatic technique. The technique is evaluated on a data base of 157 manually annotated lumbar radiographs, resulting in a final mean point-to-contour error of $0.81~\pm ~0.98$ mm for automatic segmentation. The results outperform the previous work in automatic vertebra segmentation in terms of both segmentation accuracy and failure rate, offering a both automatic and semi-automatic approach in one unifying framework. 相似文献