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排序方式: 共有467条查询结果,搜索用时 31 毫秒
91.
Dr. Maria Teresa Borrello Dr. Hanae Benelkebir Adam Lee Chak Hin Tam Manar Shafat Dr. Stuart A. Rushworth Prof. Kristian M. Bowles Leon Douglas Dr. Patrick J. Duriez Dr. Sarah Bailey Prof. Simon J. Crabb Prof. Graham Packham Prof. A. Ganesan 《ChemMedChem》2021,16(8):1316-1324
Lysine-specific demethylase 1 (LSD1/KDM1A) oxidatively removes methyl groups from histone proteins, and its aberrant activity has been correlated with cancers including acute myeloid leukemia (AML). We report a novel series of tranylcypromine analogues with a carboxamide at the 4-position of the aryl ring. These compounds, such as 5 a and 5 b with benzyl and phenethylamide substituents, respectively, had potent sub-micromolar IC50 values for the inhibition of LSD1 as well as cell proliferation in a panel of AML cell lines. The dose-dependent increase in cellular expression levels of H3K4me2, CD86, CD11b and CD14 supported a mechanism involving LSD1 inhibition. The tert-butyl and ethyl carbamate derivatives of these tranylcypromines, although inactive in LSD1 inhibition, were of similar potency in cell-based assays with a more rapid onset of action. This suggests that carbamates can act as metabolically labile tranylcypromine prodrugs with superior pharmacokinetics. 相似文献
92.
Yohanes C. Malede Julien P. Simon Torbjrn Jonsson Melanie Montgomery Kristian V. Dahl John Hald 《工业材料与腐蚀》2019,70(8):1486-1506
Ni–(35–45)Cr–4Nb alloys containing different fractions of α‐Cr were exposed to potassium chloride (KCl)‐induced corrosion. The corrosion exposures were carried out for 168 hr at 600°C in a 15% (vol/vol) H2O (g) + 5% (vol/vol) O2 (g) + N2 (g; balance) atmosphere using KCl‐free (reference) and predeposited KCl samples. To mimic the KCl deposition in real boilers, 24 hr exposures where KCl vapor condensed continuously onto samples were also performed. The corrosion attack of the studied materials increased significantly when KCl was present compared to the KCl‐free samples. For the KCl exposures, the corrosion attack drastically increased when a significant α‐Cr fraction was present. α‐Cr was either selectively attacked or dissolved through solid‐state diffusion and a layered build‐up of the outer external scale of K2CrO4 and chromia could be observed. For the in situ condensed KCl exposure, severe corrosion was observed already within the 24 hr exposure, indicating a higher corrosion rate compared with when KCl was predeposited. 相似文献
93.
The relationship between the norm square of the standardized cumulative distribution and the chi-square statistic is examined using the form of the covariance matrix as well as the projection perspective. This investigation enables us to give uncorrelated components of the chi-square statistic and to provide interpretation of these components as innovations standardizing the cumulative distribution values. The norm square of the standardized difference between empirical and theoretical cumulative distributions is also examined as an objective function for parameter estimation. Its relationship to the chi-square distance enables us to discuss the large sample properties of these estimators and a difference in their properties in the cases that the distribution is evaluated at fixed and random points. 相似文献
94.
Christian Heubner Sebastian Maletti Henry Auer Juliane Hüttl Karsten Voigt Oliver Lohrberg Kristian Nikolowski Mareike Partsch Alexander Michaelis 《Advanced functional materials》2021,31(51):2106608
The development of rechargeable batteries with high-energy density is critical for future decarbonization of transportation. Anode-free Li-ion batteries, using a bare current collector at the anode side without any excess of Li, provide the highest volumetric energy density ( > 1500 Wh L−1) among all possible cell configurations. Furthermore, elimination of the anode material coating reduces material consumption and greatly simplifies cell production, which in turn lowers costs. Although significant progress has been made recently by the application of modified current collectors, optimized cycling parameters and improved liquid electrolytes, insufficient efficiencies, and dendritic growth during lithium plating lead to poor cycle life of typically less than 100 cycles as well as safety issues. Alternatively, very recent studies have demonstrated anode-free solid-state batteries that combine the benefits of high energy anode-free cell configuration and solid-state systems with high safety, exceeding 1000 cycles. This review provides an overview of recent developments toward anode-free solid-state batteries and highlights the current issues and challenges in this nascent field. It is concluded that, although major challenges remain at the present, the lessons learned in the fields of liquid electrolytes and solid-state lithium metal batteries can accelerate the development of anode-free solid-state batteries of practical relevance. 相似文献
95.
Jesús Rodríguez-Sánchez Barbara Myszka Aldo Roberto Boccaccini Dag Kristian Dysthe 《Journal of the American Ceramic Society》2019,102(11):6980-6990
Calcium carbonate cements have emerged in the last few years as an attractive candidate for biomedical applications. They can be easily prepared by mixing water with two metastable calcium carbonate phases––amorphous calcium carbonate (ACC) and vaterite––which (re)crystallize into calcite during setting reaction. The transformation kinetics (and therefore the final surface cement composition) strongly depends on the initial mixture design and is controlled by the dissolution of ACC, whereas calcite nucleation typically controls their recrystallization in fluid batch experiments. Novel compositions are presented in this paper by incorporating organic molecules as a proxy to test their capability to carry on other biomolecules like proteins or antibiotics. The hardened samples are microporous and show excellent bioactivity rates, although their mechanical properties still remain poor. However, this would not be a handicap for in-vivo applications such as bone filling, especially in low mechanical stress locations. 相似文献
96.
Economics of fixed broadband access network strategies 总被引:2,自引:0,他引:2
Monath T. Kristian N. Cadro P. Katsianis D. Varoutas D. 《Communications Magazine, IEEE》2003,41(9):132-139
This article presents a comprehensive techno-economic evaluation of two upgrade strategy cases for broadband IP services for residential and business customers, and illustrates their respective merits and pitfalls, allowing the definition of a reasonable investment policy. The work should enable establishment of guidelines for broadband infrastructure upgrade strategies from the incumbent operator's view. Following the definition of appropriate service sets, and taking into account demand scenarios established within the project, this work has been focused on developing a techno-economic model, based on the TONIC tool. Tariff structures have been applied to compute the key economic indicators, net present value, internal rate of return, and payback period. This investment analysis was carried using the tool, which was developed by IST-TONIC. The results show that the choice of technology (Ethernet or ATM) has almost no effect on the cost level and profitability of the cases. For the suburban area, a fiber to the cabinet solution is too expensive due to heavy infrastructure investments; for dense urban and urban areas the FTTC solution is worth the investments. The FTTH/office deployment scenario is only profitable in dense urban areas (>5000 potential customers/km/sup 2/) and already highly risky in the urban area. 相似文献
97.
98.
Properties and Biotechnological Applications of Acyl‐CoA:diacylglycerol Acyltransferase and Phospholipid:diacylglycerol Acyltransferase from Terrestrial Plants and Microalgae 下载免费PDF全文
Yang Xu Kristian Mark P. Caldo Dipasmita Pal‐Nath Jocelyn Ozga M. Joanne Lemieux Randall J. Weselake Guanqun Chen 《Lipids》2018,53(7):663-688
Triacylglycerol (TAG) is the major storage lipid in most terrestrial plants and microalgae, and has great nutritional and industrial value. Since the demand for vegetable oil is consistently increasing, numerous studies have been focused on improving the TAG content and modifying the fatty‐acid compositions of plant seed oils. In addition, there is a strong research interest in establishing plant vegetative tissues and microalgae as platforms for lipid production. In higher plants and microalgae, TAG biosynthesis occurs via acyl‐CoA‐dependent or acyl‐CoA‐independent pathways. Diacylglycerol acyltransferase (DGAT) catalyzes the last and committed step in the acyl‐CoA‐dependent biosynthesis of TAG, which appears to represent a bottleneck in oil accumulation in some oilseed species. Membrane‐bound and soluble forms of DGAT have been identified with very different amino‐acid sequences and biochemical properties. Alternatively, TAG can be formed through acyl‐CoA‐independent pathways via the catalytic action of membrane‐bound phospholipid:diacylglycerol acyltransferase (PDAT). As the enzymes catalyzing the terminal steps of TAG formation, DGAT and PDAT play crucial roles in determining the flux of carbon into seed TAG and thus have been considered as the key targets for engineering oil production. Here, we summarize the most recent knowledge on DGAT and PDAT in higher plants and microalgae, with the emphasis on their physiological roles, structural features, and regulation. The development of various metabolic engineering strategies to enhance the TAG content and alter the fatty‐acid composition of TAG is also discussed. 相似文献
99.
Gmyr Robert Hinnenthal Kristian Kostitsyna Irina Kuhn Fabian Rudolph Dorian Scheideler Christian Strothmann Thim 《Natural computing》2020,19(2):375-390
Natural Computing - Motivated by the problem of manipulating nanoscale materials, we investigate the problem of reconfiguring a set of tiles into certain shapes by robots with limited computational... 相似文献
100.
A novel automatic tuning strategy is proposed. It is based on an experiment of very short duration, followed by simultaneous identification of LTI model parameters and an estimate of their error covariance. The parametric uncertainty model is subsequently exploited to design linear controllers with magnitude bounds on some closed‐loop transfer function of interest, such as the sensitivity function. The method is demonstrated through industrially relevant examples. Robustness is enforced through probabilistic constraints on the norms of the sensitivity function, while minimizing load disturbance integral error to ensure performance. To demonstrate the strength of the proposed method, identification for the mentioned examples is carried out under a high level of measurement noise. Copyright © 2016 John Wiley & Sons, Ltd. 相似文献