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121.
Steffen Vojacek Lukas Schulig Nathalie Wössner Norman Geist Prof. Dr. Walter Langel Prof. Dr. Manfred Jung Prof. Dr. Dennis Schade Prof. Dr. Andreas Link 《ChemMedChem》2019,14(8):853-864
Indoles are privileged structures in medicinal and bioorganic chemistry that are particularly well suited to serve as platforms for diversity. Among many other therapeutic areas, the indole scaffold has been used to design aromatic compounds useful to interfere with enzymes engaged in the regulation of substrate acylation status, such as sirtuins. However, the planarity of the indole ring is not necessarily optimal for all target enzymes, especially when functionalization with aromatic side chains is required. Replacement of flat scaffolds by nonplanar molecular cores dominated by sp3 hybridization is a common strategy to avoid the disadvantages associated with poor solubility and high promiscuity, while covering less-well-explored areas of chemical space. Thus, we synthesized fragment-like tetrahydroindoles suitable for fragment-based drug discovery as well as a well-characterized small library intended as multipurpose screening compounds. For proof of principle, these compounds were screened against sirtuins 1–3, enzymes known to be addressable by indoles. We found that 2,6,6-trimethyl-4-oxo-4,5,6,7-tetrahydro-1H-indole-3-carboxamides are potent and selective SIRT2 inhibitors. Compound 16 t displayed an IC50 value of 0.98 μm and could serve as exquisite starting point for hit-to-lead profiling. 相似文献
122.
High‐intensity sweeteners in espresso coffee: ideal and equivalent sweetness and time–intensity analysis 下载免费PDF全文
Bruna M. Azevedo Flávio L. Schmidt Helena M. A. Bolini 《International Journal of Food Science & Technology》2015,50(6):1374-1381
The efficient substitution of sucrose by a sweetener in beverages requires the application of some sensory techniques. First, one must determine the concentrations of the sweeteners under study, equivalent in sweetness to the ideal sucrose concentration. In addition, it is fundamental to determine which is most similar to sucrose. The objectives of this study were to determine the ideal sweetness for espresso coffee and the equivalent concentrations in sweetness of different sweeteners, as well as characterise the time–intensity profile of each sweetener in relation to sweetness. The sweeteners evaluated were sucralose, aspartame, neotame, a cyclamate/saccharin mixture (2:1) and stevia. The sucrose concentration considered ideal by consumers was 12.5% (w/v), and the equivalent concentrations of the sweeteners were 0.0159% for sucralose, 0.0549% for aspartame, 0.0016% for neotame, 0.0359% for the cyclamate/saccharin mixture and 0.0998% for stevia. The time–intensity analysis indicated that possibly the sweeteners neotame, aspartame and sucralose would be the best substitutes for sucrose. 相似文献
123.
124.
David L. Wood Jeffrey D. Quass Jianlin Li Shabbir Ahmed David Ventola Claus Daniel 《Drying Technology》2018,36(2):234-244
Processing lithium-ion battery (LIB) electrode dispersions with water as the solvent during primary drying offers many advantages over N-methylpyrrolidone (NMP). An in-depth analysis of the comparative drying costs of LIB electrodes is discussed for both NMP- and water-based dispersion processing in terms of battery pack $/kWh. Electrode coating manufacturing and capital equipment cost savings are compared for water vs. conventional NMP organic solvent processing. A major finding of this work is that the total electrode manufacturing costs, whether water- or NMP-based, contribute about 8–9% of the total pack cost. However, it was found that up to a 2?×?reduction in electrode processing (drying and solvent recovery) cost can be expected along with a $3–6?M savings in associated plant capital equipment (for a plant producing 100,000 10-kWh Plug-in Hybrid Electric Vehicle (PHEV) batteries) using water as the electrode solvent. This paper shows a different perspective in that the most important benefits of aqueous electrode processing actually revolve around capital equipment savings and environmental stewardship and not processing cost savings. 相似文献
125.
Application of high‐temperature Fenton oxidation for the treatment of sulfonation plant wastewater 下载免费PDF全文
126.
Crespo Juan-José Sánchez José L. Alfaro-Cortés Francisco J. Flich José Duato José 《The Journal of supercomputing》2021,77(11):12826-12856
The Journal of Supercomputing - Deadlock-free dynamic network reconfiguration process is usually studied from the routing algorithm restrictions and resource reservation perspective. The dynamic... 相似文献
127.
Dr. Emrah Kara Dr. Nis Valentin Nielsen Bergrun Eggertsdottir Dr. Bernd Thiede Dr. Sandip M. Kanse Dr. Geir Åge Løset 《Chembiochem : a European journal of chemical biology》2020,21(13):1875-1884
We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated. 相似文献
128.
H.C. Weigele L. Gygax A. Steiner B. Wechsler J.-B. Burla 《Journal of dairy science》2018,101(3):2370-2382
Lameness is one of the most prevalent diseases affecting the welfare of cows in modern dairy production. Lameness leads to behavioral changes in severely lame cows, which have been investigated in much detail. For early detection of lameness, knowledge of the effects of moderate lameness on cow behavior is crucial. Therefore, the behavior of nonlame and moderately lame cows was compared on 17 Swiss dairy farms. On each farm, 5 to 11 nonlame (locomotion score 1 of 5) and 2 to 7 moderately lame (locomotion score 3 of 5) cows were selected for data collection in two 48-h periods (A, B) separated by an interval of 6 to 10 wk. Based on visual locomotion scoring, 142 nonlame and 66 moderately lame cows were examined in period A and 128 nonlame and 53 moderately lame cows in period B. Between these 2 periods, the cows underwent corrective hoof trimming. Lying behavior, locomotor activity, and neck activity were recorded by accelerometers (MSR145 data logger, MSR Electronics GmbH, Seuzach, Switzerland), and feeding and rumination behaviors by noseband sensors (RumiWatch halter, ITIN + HOCH GmbH, Liestal, Switzerland). Furthermore, visits to the brush and the concentrate feeder, and the milking order position were recorded. In comparison with nonlame cows, moderately lame cows had a longer lying duration, a longer average lying bout duration, and a greater lateral asymmetry in lying duration. Average locomotor activity, locomotor activity during 1 h after feed delivery or push-ups, and average neck activity were lower in moderately lame cows. Eating time and the number of eating chews (jaw movements) were reduced in moderately lame compared with nonlame cows, whereas no effect of moderate lameness was evident for ruminating time, number of ruminating chews and boluses, and average number of ruminating chews per bolus. Moderately lame cows visited the concentrate feeder and the brush less frequently, and they were further back in the milking order compared with nonlame cows. In conclusion, nonlame and moderately lame cows differed in a biologically relevant way in many of the behavioral variables investigated in this study. Therefore, the use of these behavioral changes seems to be promising to develop a tool for early lameness detection. 相似文献
129.
L. S. Belevskii N. V. Koptseva I. V. Belevskaya Yu. Yu. Efimova 《Russian Metallurgy (Metally)》2015,2015(9):753-758
The microstructure and properties of the functional coatings formed by impact friction processing of product surfaces with a flexible tool are studied. It is established that the processing produces a hard nanostructured surface layer with fragments up to 0.13 µm in size, as it is achieved by severe plastic deformation. 相似文献
130.