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101.
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
102.
Beierlein Dennis Häussermann Dorothea Traa Yvonne Klemm Elias 《Catalysis Letters》2022,152(10):2908-2919
Catalysis Letters - We developed a rapid aging method for Ni/Al2O3 methanation catalysts mimicking the real aging in the actual application. The method is based on hydrothermal deactivation of the... 相似文献
103.
Although theoretically necessary, social capital is usually not considered within the process of asset allocation for private
investors. Both the lack of appropriate practical valuation concepts and the effort of providing and processing the required
information as input for a valuation have been obstacles to properly include social capital in this process. However, first
theoretical financial models for the evaluation of social capital have recently become available. Moreover, the fast growth
of business community websites and the technological progress in Web 2.0 tools that allow and acquire the active involvement
of users, facilitate the provision and processing of valuation-relevant information. In this paper we focus on this second
aspect and propose a social software-based concept that allows for an integration of social capital in the asset allocation
process. 相似文献
104.
Taste perception and purchase intent of oil‐in‐water spreads: effects of oil types and salt (NaCl or KCl) concentrations
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Wilfredo Alejandro Cerrato Rodriguez Damir Dennis Torrico Luis Fernando Osorio Jorge Cardona Witoon Prinyawiwatkul 《International Journal of Food Science & Technology》2017,52(10):2138-2147
Associations of sodium intake with heart‐related problems are creating awareness towards reducing sodium. Potassium chloride (KCl), a substitute for sodium chloride (NaCl), has the disadvantage of imparting bitterness at high concentrations. We evaluated physical characteristics, taste perception and purchase intent of KCl and NaCl in oil‐in‐water spreads/emulsions composed by olive, rice bran and soya bean oils. Consumers (N = 300) evaluated saltiness/bitterness of emulsions prepared with 65% oil, and NaCl (0.5% and 1.0%) or KCl (0.75% and 1.5%). Olive oil spreads (104.07–107.43 Pa s) had higher viscosity compared to other spreads (59.16–74.96 Pa s). Type of oil had significant effects on bitterness, overall taste liking and viscosity. Taste liking decreased due to bitterness of olive oil spreads (mean drop=1.72–2.43). Purchase intent was positively associated with saltiness and pH and increased with oil claims (increase = 1.3%–22.1%) compared to sodium claims (increase = 0.0%–12.9%). These findings are useful for understanding taste perception of emulsions. 相似文献
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Seung Geol Choi Dennis Hofheinz Eike Kiltz Dong Hoon Lee Moti Yung 《Information Processing Letters》2009,109(16):897-901
At CRYPTO 2004, Kurosawa and Desmedt presented a new hybrid encryption scheme that is chosen-ciphertext (CCA2) secure in the standard model. Until now it was unknown if the key encapsulation part of the Kurosawa-Desmedt scheme by itself is still CCA2-secure or not. In this note we answer this question to the negative, namely we present a simple CCA2 attack on the Kurosawa-Desmedt key encapsulation mechanism. Our attack further supports the design paradigm of Kurosawa and Desmedt to build CCA2-secure hybrid encryption from weak key encapsulation. 相似文献
110.
Previous research on perceiving spatial layout has found that people often exhibit normative biases in their perception of the environment. For instance, slant is typically overestimated and distance is usually underestimated. Surprisingly, however, the perception of height has rarely been studied. The present experiments examined the perception of height when viewed from the top (e.g., looking down) or from the bottom (e.g., looking up). Multiple measures were adapted from previous studies of horizontal extents to assess the perception of height. Across all of the measures, a large, consistent bias was found: Vertical distances were greatly overestimated, especially from the top. Secondary findings suggest that the overestimation of distance and size that occurs when looking down from a high place correlates with reports of trait- and state-level fear of heights, suggesting that height overestimation may be due, in part, to fear. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献