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101.
Dr. Holger Siebeneicher Dr. Arwed Cleve Dr. Hartmut Rehwinkel Dr. Roland Neuhaus Dr. Iring Heisler Dr. Thomas Müller Dr. Marcus Bauser Dr. Bernd Buchmann 《ChemMedChem》2016,11(20):2261-2271
Despite the long‐known fact that the facilitative glucose transporter GLUT1 is one of the key players safeguarding the increase in glucose consumption of many tumor entities even under conditions of normal oxygen supply (known as the Warburg effect), only few endeavors have been undertaken to find a GLUT1‐selective small‐molecule inhibitor. Because other transporters of the GLUT1 family are involved in crucial processes, these transporters should not be addressed by such an inhibitor. A high‐throughput screen against a library of ~3 million compounds was performed to find a small molecule with this challenging potency and selectivity profile. The N‐(1H‐pyrazol‐4‐yl)quinoline‐4‐carboxamides were identified as an excellent starting point for further compound optimization. After extensive structure–activity relationship explorations, single‐digit nanomolar inhibitors with a selectivity factor of >100 against GLUT2, GLUT3, and GLUT4 were obtained. The most promising compound, BAY‐876 [N4‐[1‐(4‐cyanobenzyl)‐5‐methyl‐3‐(trifluoromethyl)‐1H‐pyrazol‐4‐yl]‐7‐fluoroquinoline‐2,4‐dicarboxamide], showed good metabolic stability in vitro and high oral bioavailability in vivo. 相似文献
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Anaerobic methane oxidation and aerobic methane production in an east African great lake (Lake Kivu) 总被引:1,自引:0,他引:1
Fleur A.E. Roland Cédric Morana François Darchambeau Sean A. Crowe Bo Thamdrup Jean-Pierre Descy Alberto V. Borges 《Journal of Great Lakes research》2018,44(6):1183-1193
We investigated CH4 oxidation in the water column of Lake Kivu, a deep meromictic tropical lake with CH4-rich anoxic deep waters. Depth profiles of dissolved gases (CH4 and N2O) and a diversity of potential electron acceptors for anaerobic CH4 oxidation (NO3?, SO42?, Fe and Mn oxides) were determined during six field campaigns between June 2011 and August 2014. Denitrification measurements based on stable isotope labelling experiments were performed twice. In addition, we quantified aerobic and anaerobic CH4 oxidation, NO3? and SO42? consumption rates, with and without the presence of an inhibitor of SO42?-reducing bacteria activity. Aerobic CH4 production was also measured in parallel incubations with the addition of an inhibitor of aerobic CH4 oxidation. The maximum aerobic and anaerobic CH4 oxidation rates were estimated to be 27?±?2 and 16?±?8?μmol/L/d, respectively. We observed a difference in the relative importance of aerobic and anaerobic CH4 oxidation during the rainy and the dry season, with a greater role for aerobic oxidation during the dry season. Lower anaerobic CH4 oxidation rates were measured in presence of molybdate in half of the measurements, suggesting the occurrence of linkage between SO42? reduction and anaerobic CH4 oxidation. NO3? consumption and dissolved Mn production rates were never high enough to sustain the measured anaerobic CH4 oxidation, reinforcing the idea of a coupling between SO42? reduction and CH4 oxidation in the anoxic waters of Lake Kivu. Finally, significant rates (up to 0.37?μmol/L/d) of pelagic CH4 production were also measured in oxygenated waters. 相似文献
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Effect of solvent type on preparation of ethyl cellulose microparticles by solvent evaporation method with double emulsion system using focused beam reflectance measurement
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The purpose of this study was to investigate the effect of solvent type on the solidification rate of ethyl cellulose (EC) microparticles and particle size/distribution of emulsion droplets/hardened microparticles during the solvent evaporation process using focused beam reflectance measurement (FBRM). EC microparticles were prepared with a water‐in‐oil‐in‐water solvent evaporation method using various solvents, including dichloromethane, dichloromethane–methanol (1:1), ethyl acetate and chloroform. The particle size/distribution of the emulsion droplets/hardened microparticles was monitored using FBRM. The morphology of EC microparticles was characterized using scanning electron microscopy (SEM). The transformation of the emulsion droplets into solid microparticles for all solvents occurred within the first 10–90 min. The square weighted mean chord length of EC microparticles prepared using chloroform was smallest, but the chord count was not the highest. The chord length distribution (CLD) measured by FBRM showed that a larger mean particle size gave longer CLD and a lower peak of particle number. SEM data revealed that the morphology of microparticles was influenced by the type of solvent. FBRM can be employed for online monitoring of the shift in the microparticle CLD and detect transformation of emulsion droplets into solid microparticles during the solvent evaporation process. The microparticle CLD and transformation process were strongly influenced by solvent type. © 2017 Society of Chemical Industry 相似文献
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法国海洋冲浪博物馆探索大海与海浪及其在休闲产业、科学和生态方面所扮演的重要角色。设计方案由斯蒂文·霍尔建筑师事务所与索朗·法比亚合作完成。2005年,在与安瑞科·米拉莱斯/贝娜蒂塔·塔格利亚布、布罗谢特·拉宇斯·普埃约、伯纳德·屈米和让·米歇尔·维尔莫特工作室的角逐中获得胜利,赢得国际竞赛大奖。建筑形式来源于"天空下"/"大海下"的空间理念。"天空下"的凹形体量成为主要的户外广场"海洋世界"的一大特色。广场朝向天空和大海开放,视野向远方无限扩展。凹形的结构天花板形成"大海下"的展览空间。 相似文献
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Controlling micro‐ and nanofibrillar morphology of polymer blends in low‐speed melt spinning process. Part II: Influences of extrusion rate on morphological changes of a PLA/PVA blend through a capillary die
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Nguyen Hoai An Tran Harald Brünig Maria Auf der Landwehr Roland Vogel Jürgen Pionteck Gert Heinrich 《应用聚合物科学杂志》2016,133(47)
The effects of the extrusion rate on the morphological changes of poly(lactic acid) (PLA)/poly(vinyl alcohol) (PVA) blend through a capillary die were investigated. In this study, the extrusion rate or mass flow rate is altered from 0.5 g min?1 to 2 g min?1 with an increment of 0.5 g min?1. The PLA/PVA blend with a composition of 30/70 (wt %) exhibits a particle matrix morphology with dispersed PLA droplets within the PVA matrix. It is found that, the spherical or ellipsoidal dispersed PLA droplets are elongated and coalesced into rod‐like or longer ellipsoidal droplets when they pass through the capillary die. When the extrusion rate increases, the coalescence between the large PLA droplets occurs more intense. However, the changes of the extrusion rate have no strong effect on the coalescence of small droplets having diameter less than about 150 nm. © 2016 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2016 , 133, 44257. 相似文献