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1.
Sun Yibin Pfahringer Bernhard Gomes Heitor Murilo Bifet Albert 《Data mining and knowledge discovery》2022,36(5):2006-2032
Data Mining and Knowledge Discovery - Most research in machine learning for data streams has focused on classification algorithms, whereas regression methods have received a lot less attention.... 相似文献
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Dr. Lukas Kröger Dr. Constantin G. Daniliuc Deeba Ensan Sebastian Borgert Dr. Christian Nienberg Miriam Lauwers Dr. Michaela Steinkrüger Prof. Joachim Jose Dr. Markus Pietsch Prof. Bernhard Wünsch 《ChemMedChem》2020,15(10):871-881
The serine/threonine kinase CK2 modulates the activity of more than 300 proteins and thus plays a crucial role in various physiological and pathophysiological processes including neurodegenerative disorders of the central nervous system and cancer. The enzymatic activity of CK2 is controlled by the equilibrium between the heterotetrameric holoenzyme CK2α2β2 and its monomeric subunits CK2α and CK2β. A series of analogues of W16 ((3aR,4S,10S,10aS)-4-{[(S)-4-benzyl-2-oxo-1,3-oxazolidin-3-yl]carbonyl}-10-(3,4,5-trimethoxyphenyl)-4,5,10,10a-tetrahydrofuro[3,4-b]carbazole-1,3(3aH)-dione ((+)- 3 a )) was prepared in an one-pot, three-component Levy reaction. The stereochemistry of the tetracyclic compounds was analyzed. Additionally, the chemically labile anhydride structure of the furocarbazoles 3 was replaced by a more stable imide ( 9 ) and N-methylimide ( 10 ) substructure. The enantiomer (−)- 3 a (Ki=4.9 μM) of the lead compound (+)- 3 a (Ki=31 μM) showed a more than sixfold increased inhibition of the CK2α/CK2β interaction (protein-protein interaction inhibition, PPII) in a microscale thermophoresis (MST) assay. However, (−)- 3 a did not show an increased enzyme inhibition of the CK2α2β2 holoenzyme, the CK2α subunit or the mutated CK2α′ C336S subunit in the capillary electrophoresis assay. In the pyrrolocarbazole series, the imide (−)- 9 a (Ki=3.6 μM) and the N-methylimide (+)- 10 a (Ki=2.8 μM) represent the most promising inhibitors of the CK2α/CK2β interaction. However, neither compound could inhibit enzymatic activity. Unexpectedly, the racemic tetracyclic pyrrolocarbazole (±)- 12 , with a carboxy moiety in the 4-position, displays the highest CK2α/CK2β interaction inhibition (Ki=1.8 μM) of this series of compounds. 相似文献
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Freddy A. Bernal Dr. Marcel Kaiser Prof. Dr. Bernhard Wünsch Prof. Dr. Thomas J. Schmidt 《ChemMedChem》2020,15(1):68-78
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model. 相似文献
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The curing of wood adhesives has so far been evaluated on a basis of parameters, which offer process optimization only to a small degree. However, the curing becomes analyzable in detail by using oscillation measurements and a test setup adapted to the bonding process. With time sweep measurements, the adhesion process can be divided into characteristic ranges of molecular and structural processes. This method is presented and analyzed using a polyurethane prepolymer for joining wood-based materials. 相似文献
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David Bernhard Thomas Kadyk Ulrike Krewer Sebastian Kirsch 《International Journal of Hydrogen Energy》2021,46(26):13791-13805
In this work, proton exchange membrane fuel cell cathodes are degraded with accelerated-stress-tests.These PtCo containing cathodes are analyzed at begin-of-life and end-of-test with a dedicated diagnostic procedure. For every individual load point, the oxygen transport resistance and voltage losses due to the formation of platinum oxides were obtained in addition to commonly measured electrochemical surface area, high frequency resistance, as well as cathode ionomer resistance. These data were used to break down the voltage losses into six different contributors. With this break down, performance gains and performance losses were determined at end-of-test. At low current densities, it was found that voltage losses due to degradation are dominated by the loss of specific activity and catalyst surface area - in line with the state-of-the-art knowledge. But by quantifying the losses from platinum oxide formation explicitly, we show that end-of-test an unassigned voltage loss is not only present at highest current densities, but already at low current density. More precisely, the unassigned voltage loss shows a linear increase with decreasing half cell voltage and is independent from the chosen accelerated stress test. As this unassigned loss depends on half cell voltage, it might arise from ionomer adsorption. 相似文献
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While renewable heat makes up only 13 % of overall German heat consumption, the share of renewable electricity produced from wind, solar, water, and geothermal power already reached 36 % of overall electricity consumption in 2017. One measure to support the integration of renewable heat in the German energy system is the use of heat storage systems. Although water‐based heat storage systems for temperatures up to 100 °C are state of the art, systems for temperatures up to several hundred degrees Celsius are still under investigation or in the demonstration phase. Therefore, this work focuses on the development of a simulation model for analyzing and engineering fixed‐bed thermal storage systems that are filled with an inert bulk material such as stone fragments. 相似文献