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991.
992.
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
993.
Structured catalysts consisting of metal sheets on which Raney nickel was deposited by the thermal spraying method were tested for the liquid‐phase hydrogenation of glucose to sorbitol and 2‐nitrotoluene to 2‐methylaniline, used as model reactions. Catalytic tests performed in a bench‐scale (1 L) reactor showed that the catalytic activity of Raney Ni sheets is significantly higher than the one of the pellets used for fixed‐bed applications, but lower than the activity of the powder catalyst used in slurry mode. The activity could be significantly improved when applying a two‐phase co‐current flow through a monolith. In this case, the activity was superior to the one obtained with the slurry catalyst. These results confirm the potential of Raney Ni monoliths as structured catalysts. 相似文献
994.
The standardisation of packaging and containers for product handling has potential benefits from transportation, material handling and environmental perspectives. Likewise, standardised modular containers play an important role in the Physical Internet (PI). To support implementation of standard modular containers, we introduce a mathematical model to select a requisite number of modular containers to pack a set of products to maximise space utilisation. A decomposition-based solution methodology is developed and presented. Computational results from industry-based problem instances indicate that using standardised modular containers results in increased space utilisation at the unit load level. This finding substantiates the use of modular containers in moving toward the PI. 相似文献
995.
Lina R. Nih Elias Sideris S. Thomas Carmichael Tatiana Segura 《Advanced materials (Deerfield Beach, Fla.)》2017,29(32)
With the number of deaths due to stroke decreasing, more individuals are forced to live with crippling disability resulting from the stroke. To date, no therapeutics exist after the first 4.5 h after the stroke onset, aside from rest and physical therapy. Following stroke, a large influx of astrocytes and microglia releasing proinflammatory cytokines leads to dramatic inflammation and glial scar formation, affecting brain tissue's ability to repair itself. Pathological conditions, such as a stroke, trigger neural progenitor cells (NPCs) proliferation and migration toward the damaged site. However, these progenitors are often found far from the cavity or the peri‐infarct tissue. Poststroke tissue remodeling results in a compartmentalized cavity that can directly accept a therapeutic material injection. Here, this paper shows that the injection of a porous hyaluronic acid hydrogel into the stroke cavity significantly reduces the inflammatory response following stroke while increasing peri‐infarct vascularization compared to nonporous hydrogel controls and stroke only controls. In addition, it is shown that the injection of this material impacts NPCs proliferation and migration at the subventricular zone niche and results, for the first time, in NPC migration into the stroke site. 相似文献
996.
Christian Immanuel Müller Thomas Rauscher Andreas Schmidt Thomas Schubert Thomas Weißgärber Bernd Kieback Lars Röntzsch 《International Journal of Hydrogen Energy》2014
In this work different amorphous melt-spun Fe-alloys (Fe82B18, Fe80Si10B10, Fe60Co20Si10B10) were investigated as cathode materials for the alkaline electrolysis of water. In particular, the influence of cobalt as well as the metalloids boron and silicon on the activity for the hydrogen evolution reaction (HER) was studied in 1 M KOH at 298 K using cyclic voltammetric, galvanostatic and polarization techniques. The electrocatalytic activity was evaluated in the view of the overpotential. It was found that cyclic voltammetric techniques can be used to activate the melt-spun Fe-alloys strongly. Different cyclic voltammetric activation procedures are discussed and the influence of the sweep rate and the potential window on the HER activity was elucidated. The experimental data indicate that the addition of metalloids and, most importantly, of cobalt improves the HER activity of the materials. Thus, the overpotential can be reduced by 200 mV compared to polycrystalline Ni. 相似文献
997.
Markus F. Weber Gabriele Poxleitner Elke Hebisch Erwin Frey Madeleine Opitz 《Journal of the Royal Society Interface》2014,11(96)
Dispersal of species is a fundamental ecological process in the evolution and maintenance of biodiversity. Limited control over ecological parameters has hindered progress in understanding of what enables species to colonize new areas, as well as the importance of interspecies interactions. Such control is necessary to construct reliable mathematical models of ecosystems. In our work, we studied dispersal in the context of bacterial range expansions and identified the major determinants of species coexistence for a bacterial model system of three Escherichia coli strains (toxin-producing, sensitive and resistant). Genetic engineering allowed us to tune strain growth rates and to design different ecological scenarios (cyclic and hierarchical). We found that coexistence of all strains depended on three strongly interdependent factors: composition of inoculum, relative strain growth rates and effective toxin range. Robust agreement between our experiments and a thoroughly calibrated computational model enabled us to extrapolate these intricate interdependencies in terms of phenomenological biodiversity laws. Our mathematical analysis also suggested that cyclic dominance between strains is not a prerequisite for coexistence in competitive range expansions. Instead, robust three-strain coexistence required a balance between growth rates and either a reduced initial ratio of the toxin-producing strain, or a sufficiently short toxin range. 相似文献
998.
We report on a mutual correlation between the substrate temperature during semiconductor deposition and the surface energy of the gate dielectric on the charge carrier mobility in bottom gate top contact organic field effect transistors (OFETs) with N,N′-diphenyl-3,4,9,10-perylene tetracarboxylic diimide (DP-PDI) as organic semiconductor. 相似文献
999.
Mohamad-Ali Mortada Thomas Carroll III Soumaya Yacout Aouni Lakis 《Journal of Intelligent Manufacturing》2012,23(2):289-302
There is a small subset of any repairable component population that can develop a failure mode outside the scope of the standard
repair and overhaul procedures, which makes them “rogue”. When this happens, a Darwinian-like “natural selection” phenomenon
ensures that they will be placed in the most disadvantageous position in the asset management program, negatively affecting
multiple aspects of the operational and maintenance organizations. Rogue components have long plagued the airline industry
and created havoc in their asset management programs. In this paper, we describe how these rogues develop, outline the natural
selection process that leads to their hampering the asset management program, and examine some of the negative impacts that
ensue. Then we propose a Condition based maintenance approach to control the development of these components. We explore the
use of a supervised learning data mining technique called Logical analysis of data (LAD) in CBM for the purpose of detecting
rogues within a population of repairable components. We apply the resulting LAD based decision model on an inventory of turbo
compressors belonging to an airline fleet. Finally, we evaluate the applicability of LAD to the rogue component detection
problem and review its efficiency as a decision model for this type of problem. 相似文献
1000.
Mihaela Habeanu Agnès Thomas Esperanza Bispo Mylène Gobert Dominique Gruffat Denys Durand Dominique Bauchart 《Meat science》2014
The effects of extruded linseed and rapeseed on lipids and FA composition of total, polar and neutral lipids of longissimus thoracis (LT) and semitendinosus (ST) muscles were investigated in 21 Normand cull cows. Animals were assigned in a 100d finishing period to straw (30%) and concentrate (70%) based (C) or the same diet supplemented with linseed (L) or with rapeseed (66%) plus linseed (33%) (RL). Beef polar and neutral lipids were purified by liquid chromatography and their FA analysed by GLC. Trans and cis 18:1, purified by HPLC from total FA methyl esters, were analysed by GLC–MS. L and LR diets did not increase beef lipid deposition, but had modified FA composition of both LT and ST muscles in favouring deposition of 18:3n-3 and 9cis,11tr 18:2 (CLA), mainly to the detriment of 18:1?9 cis (neutral lipids) and 18:2n-6 (polar lipids). However, they did not favour deposition of LC n-3 PUFA in the two muscles, but had increased deposition of trans 18:1 significantly, especially of ?13tr to ?16tr isoforms to the detriment of ?10tr 18:1 (L diet) and of ?11tr 18:1 (RL diet). 相似文献