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排序方式: 共有213条查询结果,搜索用时 15 毫秒
131.
Adam Hotra Priya Ragunathan Pearly Shuyi Ng Pattarakiat Seankongsuk Amaravadhi Harikishore Jickky Palmae Sarathy Wuan‐Geok Saw Umayal Lakshmanan Patcharaporn Sae‐Lao Nitin Pal Kalia Joon Shin Revathy Kalyanasundaram Sivaraj Anbarasu Krupakar Parthasarathy Chaudhari Namrata Pradeep Harshyaa Makhija Peter Drge Anders Poulsen Jocelyn Hui Ling Tan Kevin Pethe Thomas Dick Roderick W. Bates Gerhard Grüber 《Angewandte Chemie (International ed. in English)》2020,59(32):13295-13304
The F1FO‐ATP synthase is required for growth and viability of Mycobacterium tuberculosis and is a validated clinical target. A mycobacterium‐specific loop of the enzyme's rotary γ subunit plays a role in the coupling of ATP synthesis within the enzyme complex. We report the discovery of a novel antimycobacterial, termed GaMF1, that targets this γ subunit loop. Biochemical and NMR studies show that GaMF1 inhibits ATP synthase activity by binding to the loop. GaMF1 is bactericidal and is active against multidrug‐ as well as bedaquiline‐resistant strains. Chemistry efforts on the scaffold revealed a dynamic structure activity relationship and delivered analogues with nanomolar potencies. Combining GaMF1 with bedaquiline or novel diarylquinoline analogues showed potentiation without inducing genotoxicity or phenotypic changes in a human embryonic stem cell reporter assay. These results suggest that GaMF1 presents an attractive lead for the discovery of a novel class of anti‐tuberculosis F‐ATP synthase inhibitors. 相似文献
132.
Yan Huang Haifeng Li Xiaoxiao He Xiaohai Yang Li Li Songyang Liu Zhen Zou Kemin Wang Jianbo Liu 《中国化学快报》2020,31(3):787-791
A novel near-infrared light photothemal-activated H2S-donating nanocomposite hydrogel was developed,through combination of a thermo-labile H2S donor and photothermal nanoparticles in agarose hydrogel.The polyethylenimine dithiocarbamate polymer,a thermo-labile compound,was synthesized as a novel H2S donor.The combination of a thermo-labile hydrogen sulfide donor and photothermal nanoparticles enabled the generation of H2S in agarose hydrogel upon irradiation with near-infrared light.The ability to modulate the photoirradiation for controlled generation and spatiotemporally release of H2S are its specific advantages.This photothermal spatiotemporally controlled H2S-releasing strategy was successfully applied to anti-inflammation treatment in a rat model,demonstrating its utility as a novel H2S-based therapeutic approach. 相似文献
133.
Yufan Zhou Juan Yao Yuanzhao Ding Jiachao Yu Xin Hua James E. Evans Xiaofei Yu David B. Lao David J. Heldebrant Satish K. Nune Bin Cao Mark E. Bowden Xiao-Ying Yu Xue-Lin Wang Zihua Zhu 《Journal of the American Society for Mass Spectrometry》2016,27(12):2006-2013
In situ liquid secondary ion mass spectrometry (SIMS) enabled by system for analysis at the liquid vacuum interface (SALVI) has proven to be a promising new tool to provide molecular information at solid–liquid and liquid–vacuum interfaces. However, the initial data showed that useful signals in positive ion spectra are too weak to be meaningful in most cases. In addition, it is difficult to obtain strong negative molecular ion signals when m/z>200. These two drawbacks have been the biggest obstacle towards practical use of this new analytical approach. In this study, we report that strong and reliable positive and negative molecular signals are achievable after optimizing the SIMS experimental conditions. Four model systems, including a 1,8-diazabicycloundec-7-ene (DBU)-base switchable ionic liquid, a live Shewanella oneidensis biofilm, a hydrated mammalian epithelia cell, and an electrolyte popularly used in Li ion batteries were studied. A signal enhancement of about two orders of magnitude was obtained in comparison with non-optimized conditions. Therefore, molecular ion signal intensity has become very acceptable for use of in situ liquid SIMS to study solid–liquid and liquid–vacuum interfaces. 相似文献
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As the controllability of complex networks has attracted much attention recently, how to design and optimize the robustness of network controllability has become a common and urgent problem in the engineering field. In this work, we propose a method that modifies any given network with strict structural perturbation to effectively enhance its robustness against malicious attacks, called dynamic optimization of controllability. Unlike other structural perturbations, the strict perturbation only swaps the links and keeps the in- and out-degree unchanged. A series of extensive experiments show that the robustness of controllability and connectivity can be improved dramatically. Furthermore, the effectiveness of our method is explained from the views of underlying structure. The analysis results indicate that the optimization algorithm makes networks more homogenous and assortative. 相似文献
137.
指数跟踪问题的广义双线性规划模型 总被引:2,自引:0,他引:2
劳剑勇 《应用数学与计算数学学报》2004,18(1):85-91
本文对指数跟踪问题建立了一种广义的双线性规划模型,其中考虑了交易费用、持仓限制与重平衡问题.根据该模型的特殊结构,本文给出了近似规划算法,通过逐次逼近的线性规划求解最优指数跟踪问题. 相似文献
138.
As an "unretained" marker, 1,3,5-tri-tert-butylbenzene (TTBB) has been commonly used to measure the hold-up volume. Despite many racemates have been resolved on Chiralcel OJ column, the hold-up volume of the column is still not well characterized. The aim of this work was to evaluate the chromatographic behavior of TTBB on the OJ column, and its application in estimating the effective phase ratio and thermodynamic parameters. The hold-up volume was affected not only by the mobile phase composition but also the solvents used for dissolving TTBB. A higher concentration of TTBB (0.500 mg/mL) showed a better reproducibility than when used at a lower concentration. After correction for thermal expansion of the mobile phase, TTBB was found to have slight retention on the OJ phase. The effective phase ratio increased with an increase in the temperature and decrease in the strength of the mobile phase. The enthalpy and entropy of enantiomers of imidazolinone herbicides were independent of the temperature in a linear van't Hoff plot when the effective phase ratio was changed. This study shows that, based on the hold-up volume from TTBB, thermodynamic evaluation with parameters derived from the distribution constant is valuable for understanding chromatographic retention and enantioseparation mechanisms of chiral analytes. 相似文献
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