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Dr. Raysa Khan Tareque Dr. Storm Hassell-Hart Dr. Tobias Krojer Dr. Anthony Bradley Dr. Srikannathasan Velupillai Dr. Romain Talon Dr. Michael Fairhead Dr. Iain J. Day Kamlesh Bala Dr. Robert Felix Dr. Paul D. Kemmitt Prof. Paul Brennan Prof. Frank von Delft Dr. Laura Díaz Sáez Prof. Kilian Huber Prof. John Spencer 《ChemMedChem》2020,15(24):2513-2520
Combined photochemical arylation, “nuisance effect” (SNAr) reaction sequences have been employed in the design of small arrays for immediate deployment in medium-throughput X-ray protein–ligand structure determination. Reactions were deliberately allowed to run “out of control” in terms of selectivity; for example the ortho-arylation of 2-phenylpyridine gave five products resulting from mono- and bisarylations combined with SNAr processes. As a result, a number of crystallographic hits against NUDT7, a key peroxisomal CoA ester hydrolase, have been identified. 相似文献
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Hypoxia formation and breakdown were tracked during 2015 in Muskegon Lake estuary at multiple locations, and five years (2011–2015) of time-series buoy observatory data were evaluated for the effect of episodic wind-events on lake mixing. Bi-weekly water temperature and dissolved oxygen (DO) profiles at four locations revealed that hypoxia occurred at all sites and persisted for 2–3 months during summer 2015. On one date in late-summer, up to 24% of the lake’s volume was estimated to be mildly hypoxic (DO < 4 mg L?1) as defined by lake sturgeon requirements. Patterns of wind speed and water column stability in late spring indicated that high winds and low stability delayed the onset of hypoxia while in late summer low winds and high stability delayed degradation of hypoxia. Wind speeds appear to play a great role in the interannual variability of stratification and subsequent hypoxia. Water temperature and DO profiles taken before and after one mid-summer mixing event (wind speed >7.7 m s?1 for 10 h), indicated that while the wind was unable to completely mix the entire water column, it deepened the epilimnion by ~1.5 m and sheared a thin layer from the upper hypolimnion. By entraining internally loaded nutrients, such episodic wind-events may initiate and sustain algal blooms in nutrient limited surface waters. Quantifying the variable role of wind and mixing events will be key to integrating limnological processes into climate models of the future. 相似文献
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Dr. Ivan A. Yaremenko Dr. Paolo Coghi Parichat Prommana Congling Qiu Peter S. Radulov Yuanqing Qu Yulia Yu. Belyakova Dr. Enrico Zanforlin Dr. Vladimir A. Kokorekin Yuki Yu Jun Wu Prof. Fabrice Fleury Dr. Chairat Uthaipibull Dr. Vincent Kam Wai Wong Prof. Alexander O. Terent'ev 《ChemMedChem》2020,15(13):1118-1127
This article discloses a new horizon for the application of peroxides in medical chemistry. Stable cyclic peroxides are demonstrated to have cytotoxic activity against cancer cells; in addition a mechanism of cytotoxic action is proposed. Synthetic bridged 1,2,4,5-tetraoxanes and ozonides were effective against HepG2 cancer cells and some ozonides selectively targeted liver cancer cells (the selectivity indexes for compounds 11 b and 12 a are 8 and 5, respectively). In some cases, tetraoxanes and ozonides were more selective than paclitaxel, artemisinin, and artesunic acid. Annexin V flow-cytometry analysis revealed that the active ozonides 22 a and 23 a induced cell death of HepG2 by apoptosis. Further study showed that compounds 22 a and 23 a exhibited a strong inhibitory effect on P-glycoprotein (P-gp/ABCB5)-overexpressing HepG2 cancer cells. ABCB5 is a key player in the multidrug-resistant phenotype of liver cancer. Peroxides failed to demonstrate a direct correlation between oxidative potential and their biological activity. To our knowledge this is the first time that peroxide diastereoisomers have been found to show stereospecific antimalarial action against the chloroquine-sensitive 3D7 strain of Plasmodium falciparum. Stereoisomeric ozonide 12 b is 11 times more active than stereoisomeric ozonide 12 a (IC50=5.81 vs 65.18 μm ). Current findings mean that ozonides merit further investigation as potential therapeutic agents for drug-resistant hepatocellular carcinoma. 相似文献
5.
Li Zhang Huiqun Yuan Sheng-Hung Chang Anthony Lam 《The International Journal of Advanced Manufacturing Technology》2020,107(3):1081-1089
With the continuous development of the Internet of Things technology and the proposal of “Made in China 2025”, the construction of IoT applicat 相似文献
6.
Carlos Calvo Anthony Mazzei 《世界电子元器件》2006,(3):46-46,48,50,52
精确的RF功率管理是现代无线发射器的热点话题,从基站的功率放大器保护到移动应用中的延长电池使用时间,它都有很多的优点。RF功率监测器,比如对数放大器,允许RF功率测量系统在一个较宽的范围监控和动态调整发射功率。尽管近几年来功率监测的精度已经有了很大改进,但是对于像那些需要高功率发射的应用甚至受到0dB功率监测误差微小变化引起的显著影响。因此这也促使检测器性能不断提高。 相似文献
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Highly degenerate primers to conserved regions of the eukaryotic phosphoinositol-specific phospholipase C (PLC) were used to amplify fragments of plant PLCs from Arabidopsis thaliana genomic DNA. Eight completely different fragment sequences that showed high homology to PLCs of both animals and plants were isolated. The variation between these putative PLCs was high and suggests that, like animals, plants have multiple isoforms of PLC. Using one of the PCR clones, we isolated a corresponding full-length Arabidopsis PLC gene (ATHATPLC1G), and sequence analysis indicated that it was most like a delta-type PLC. This gene is 2.5 kb and contains seven introns, all but one of which has intron/exon border sequences that conform to the Arabidopsis consensus. The structural complexity of the gene is relatively simple compared to mammalian beta-type PLCs that can be 15 kb long with up to 30 introns. The plant gene is a single copy and was mapped to four Arabidopsis YACs, one located on chromosome 2. The promoter region contained two TATA-like elements at -43 and -185 and other putative regulatory elements that suggest that this PLC is hormonally regulated. This is the first plant PLC gene and the first delta type-PLC gene from a higher organism to be sequenced. 相似文献
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Anthony E. Bentley 《国际强度与非线性控制杂志
》1994,4(1):119-160
》1994,4(1):119-160
Two different control systems were developed using quantitative feedback theory for weld quality improvement. The first application to be discussed was designed for the resistance pinch welding process and uses electrode displacement and force as feedback parameters. A correlation between weld quality and electrode displacement is established for constant electrode force. The system is capable of producing repeatable welds of consistent quality, with wide variations in weld parameters. This is the first time feedback control has been successfully applied to pinch welding. The second example presented in this paper was developed for penetration control of the gas-tungsten-arc welding process. The feedback signal is obtained by measuring the amount of light emitted from the back side of the weld. Welds of constant penetration have been demonstrated in tests with travel speeds varying from 1.5 to 6 inches per minute and with 200 per cent changes in part thickness. 相似文献