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991.
992.
Andrea Wangorsch Anuja Kulkarni Annette Jamin Jelena Spiric Julia Brcker Jens Brockmeyer Vera Mahler Natalia Blanca‐Lpez Marta Ferrer Miguel Blanca Maria Torres Paqui Gomez Joan Bartra Alba García‐Moral María J. Goikoetxea Stefan Vieths Masako Toda Gianni Zoccatelli Stephan Scheurer 《Molecular nutrition & food research》2020,64(19)
993.
994.
Linda Heintze Dorian Schmidt Theo Rodat Lydia Witt Julia Ewert Malte Kriegs Rainer Herges Christian Peifer 《International journal of molecular sciences》2020,21(23)
In this study, we aimed at the application of the concept of photopharmacology to the approved vascular endothelial growth factor receptor (VEGFR)-2 kinase inhibitor axitinib. In a previous study, we found out that the photoisomerization of axitinib’s stilbene-like double bond is unidirectional in aqueous solution due to a competing irreversible [2+2]-cycloaddition. Therefore, we next set out to azologize axitinib by means of incorporating azobenzenes as well as diazocine moieties as photoresponsive elements. Conceptually, diazocines (bridged azobenzenes) show favorable photoswitching properties compared to standard azobenzenes because the thermodynamically stable Z-isomer usually is bioinactive, and back isomerization from the bioactive E-isomer occurs thermally. Here, we report on the development of different sulfur–diazocines and carbon–diazocines attached to the axitinib pharmacophore that allow switching the VEGFR-2 activity reversibly. For the best sulfur–diazocine, we could verify in a VEGFR-2 kinase assay that the Z-isomer is biologically inactive (IC50 >> 10,000 nM), while significant VEGFR-2 inhibition can be observed after irradiation with blue light (405 nm), resulting in an IC50 value of 214 nM. In summary, we could successfully develop reversibly photoswitchable kinase inhibitors that exhibit more than 40-fold differences in biological activities upon irradiation. Moreover, we demonstrate the potential advantage of diazocine photoswitches over standard azobenzenes. 相似文献
995.
AbstractIn this paper, we examine how to understand housing as a relational process. Drawing on research in three diverse cities, we stage an unlikely dialogue that brings together narratives of housing across the global North–South divide. In doing so, we are concerned with thinking housing relationally in two broad senses: first, housing as a relational composite of economy, space, politics, legality and materials, structured by particular relations of power and resource inequality. Second, housing as a space of learning through comparison, which connects geographically and culturally in distinct cities. What do we learn about relational thinking with regards to housing when we compare it across the global North–South divide? In response, we explore a dialogue between a set of cities often off-the-map in debates on housing and urban research: Gateshead (UK), Kampala (Uganda) and Tirana (Albania). In comparing how housing is produced, distributed and inhabited, we seek to contribute to a wider understanding of the relationalities of housing. 相似文献
996.
Julia Hapke F. GehrigN. Huber K. SchulteE.T. Lilleodden 《Composites Science and Technology》2011,71(9):1242-1249
Here we present an in situ scanning electron microscopy (SEM) investigation of the compressive failure of unidirectional (UD) carbon fibre reinforced polymer (CFRP) composites with varying pre-existing void content. The experiments were carried out within a dual beam microscope, which couples a SEM with a focused ion beam (FIB), allowing sub-surface investigations of damage. In these tests, the specimen is monitored during the entire loading history, allowing the correlation of microstructural changes and the evolving load-displacement behaviour. Therefore, loading characteristics can be linked directly to failure events. Observations of the sequence of events leading to failure showed direct fibre deflection into a kinked shape eventually followed by fibre fracture. Failure of void-containing CFRP was shown to depend on the void shape as well as the proximity of the void to the kink band. In some cases voids stopped the propagation of kink bands, while in other cases the void caused the kink to deflect in a new direction. The failure structure was observed to change with time, both during hold-load segments as well as after unloading. Through cross-sectional ion beam milling in the unloaded state, the sub-surface damage was observed and shown to be similar to that observed at the surface. 相似文献
997.
Julia R. Sanem Darin J. Erickson Patricia C. Rutledge Kathleen M. Lenk Toben F. Nelson Rhonda Jones-Webb Traci L. Toomey 《Accident; analysis and prevention》2015
All states in the U.S. prohibit alcohol-impaired driving but active law enforcement is necessary for effectively reducing this behavior. Sobriety checkpoints, saturation patrols, open container laws, and media campaigns related to enforcement efforts are all enforcement-related strategies for reducing alcohol-impaired driving. We conducted surveys of all state patrol agencies and a representative sample of local law enforcement agencies to assess their use of alcohol-impaired driving enforcement-related strategies and to determine the relationship between these enforcement-related strategies and self-reported alcohol-impaired driving behavior obtained from the Behavioral Risk Factor Surveillance System. We found that sobriety checkpoints, saturation patrols, and enforcement of open container laws were associated with a lower prevalence of alcohol-impaired driving but, more importantly, a combination of enforcement-related strategies was associated with a greater decrease in alcohol-impaired driving than any individual enforcement-related activity. In addition, alcohol-impaired driving enforcement-related strategies were associated with decreased alcohol-impaired driving above and beyond their association with decreased binge drinking. Results suggest law enforcement agencies should give greater priority to using a combination of strategies rather than relying on any one individual enforcement activity. 相似文献
998.
We report on the initial and later stages of apatite formation from simulated body fluid on titania with different surface morphologies (compact or nanotubular) and different crystal structures (anatase or amorphous). The nanotubular layers were fabricated by electrochemical anodization in fluoride-containing electrolytes. The study investigates the enhanced apatite deposition on titania nanotubes. In the initial stages of apatite growth, more nuclei are formed on the nanotubular surface than on flat compact TiO2. While the crystallographic structure of the substrate plays a less important role than the morphology in the initial nucleation stages, it is of great importance in the later stages of apatite crystal growth. The nanotubular morphology combined with an anatase structure leads to the formation of apatite layers with a thickness of >6 nm in less than 2 days. No stable apatite layers can be observed on amorphous TiO2 films, neither on compact nor on nanotubular substrates.XPS, FT-IR and XRD measurements reveal that carbonated hydroxyapatite (CHA) of low crystallinity is formed on annealed nanotubular and compact titania.Electrochemically grown and annealed TiO2 nanotube arrays having anatase structure are expected to be a good precursor system for the formation of CHA and thus for the preparation of osseointegrative implants. 相似文献
999.
Current energy and GHG emissions policies either focus directly on emissions or promote renewable production and the implementation of specific efficiency measures. Meanwhile, the fundamental structure of the energy market based on profits through energy throughput remains largely unchallenged. This policy oversight prevents the transition to an energy economy in which profits are based on energy services delivered at the lowest energy cost: a performance-based energy economy (PBEE). The PBEE applies the combined concepts of the performance economy and energy services to the energy sector. Energy Service Companies (ESCOs) are discussed as an example of PBEE practices. The implications for energy suppliers and consumers as well as the conditions for PBEE diffusion and consequences for technological change are also explored. The expected environmental, social and economic benefits are described. However, absolute consumption and emissions reductions may prove elusive due to the rebound effect. In order to forestall rebound-led increases, complementary policy measures likely to lead to absolute reductions are required. 相似文献
1000.
Weiler Julia A.; Bellebaum Christian; Brüne Martin; Juckel Georg; Daum Irene 《Canadian Metallurgical Quarterly》2009,23(5):571
Recent models assume that some symptoms of schizophrenia originate from defective reward processing mechanisms. Understanding the precise nature of reward-based learning impairments might thus make an important contribution to the understanding of schizophrenia and the development of treatment strategies. The present study investigated several features of probabilistic reward-based stimulus association learning, namely the acquisition of initial contingencies, reversal learning, generalization abilities, and the effects of reward magnitude. Compared to healthy controls, individuals with schizophrenia exhibited attenuated overall performance during acquisition, whereas learning rates across blocks were similar to the rates of controls. On the group level, persons with schizophrenia were, however, unable to learn the reversal of the initial reward contingencies. Exploratory analysis of only the subgroup of individuals with schizophrenia who showed significant learning during acquisition yielded deficits in reversal learning with low reward magnitudes only. There was further evidence of a mild generalization impairment of the persons with schizophrenia in an acquired equivalence task. In summary, although there was evidence of intact basic processing of reward magnitudes, individuals with schizophrenia were impaired at using this feedback for the adaptive guidance of behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved) 相似文献