Active Transport of Hepatotoxic Pyrrolizidine Alkaloids in HepaRG Cells

1,2-unsaturated pyrrolizidine alkaloids (PAs) are secondary plant metabolites occurring as food contaminants that can cause severe liver damage upon metabolic activation in hepatocytes. However, it is yet unknown how these contaminants enter the cells. The role of hepatic transporters is only at the beginning of being recognized as a key determinant of PA toxicity. Therefore, this study concentrated on assessing the general mode of action of PA transport in the human hepatoma cell line HepaRG using seven structurally different PAs. Furthermore, several hepatic uptake and efflux transporters were targeted with pharmacological inhibitors to identify their role in the uptake of the PAs retrorsine and senecionine and in the disposition of their N-oxides (PANO). For this purpose, PA and PANO content was measured in the supernatant using LC-MS/MS. Also, PA-mediated cytotoxicity was analyzed after transport inhibition. It was found that PAs are taken up into HepaRG cells in a predominantly active and structure-dependent manner. This pattern correlates with other experimental endpoints such as cytotoxicity. Pharmacological inhibition of the influx transporters Na⁺/taurocholate co-transporting polypeptide (SLC10A1) and organic cation transporter 1 (SLC22A1) led to a reduced uptake of retrorsine and senecionine into HepaRG cells, emphasizing the relevance of these transporters for PA toxicokinetics.     

The effectiveness of adaptive versus non-adaptive learning with digital educational games

For the training of academic skills, digital educational games with integrated adaptivity are promising. Adaptive games are considered superior to non-adaptive games, because they constantly assess children's performance, and accordingly adapt the difficulty of the tasks corresponding to the children's individual level. However, empirical evidence with regard to the effectivity of adaptive compared to non-adaptive games is limited. A study was conducted with 191 children from the third year of Kinder garten who were enrolled in one of three conditions, that is, playing an adaptive version of the reading game (RG), a non-adaptive version of the RG or training with pen-and-paper exercises. In all three conditions, children trained emergent reading (phonological awareness and letter knowledge) once a week for 30 min over a period of 5 weeks. Children's performance on cognitive (phonological awareness, letter knowledge, reading fluency) and non-cognitive (motivation, self-concept) factors was assessed. Results revealed a significant improvement in phonological awareness and letter knowledge in all conditions. However, no differences between the conditions were observed with respect to children's improvement on phonological awareness and letter knowledge or on their post-test scores for reading fluency. With regard to motivation and self-concept, again, no differences in these non-cognitive factors were observed across conditions.     

Synchrony effects in inhibitory control over thought and action.

Two experiments explore whether synchrony between peak circadian arousal periods and time of testing influences inhibitory efficiency for younger and older adults. Experiment 1 assesses inhibitory control over no-longer-relevant thoughts, and Experiment 2 assesses control over unwanted but strong responses, as well as performance on neuropsychological tasks that index frontal function. Inhibitory control is greatest at optimal times for both age groups and is generally greater for younger than for older adults. Performance on 2 neuropsychological measures (Stroop and Trails) also changes over the day, at least for older adults, and is correlated with inhibitory indexes, suggesting that for older adults changes in inhibition may be mediated by circadian variations in frontal functioning. By contrast, access to well-learned responses is not vulnerable to synchrony or age effects. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Hydrogen-assisted cracking

This article reviews a number of case studies involving hydrogen-assisted cracking in steels. Before the case studies are presented, the current state of understanding of hydrogen-assisted cracking is briefly reviewed. At present there are two leading approaches to the development of a mechanism of hydrogen-assisted cracking, one based upon bond weakening, and the other upon strain localization. As the case studies illustrate, hydrogen-assisted cracking can lead to failures in perhaps unexpected circumstances. The need for the wider dissemination of information about hydrogen cracking to design engineers is indicated.     

Economic Comparison of NdFeB and Hard Ferrites in Automotive Applications

With the increasing use of electric motors in automobiles—in some cases as many as 100 electric motors per vehicle—alternatives to ferrite magnetic materials are under consideration. If more powerful magnetic materials could be implemented, size reductions in these motors could result in curb weight reductions that lead to improved fuel economy. NdFeB magnets are attractive as potential replacement materials, due to their higher flux density and thus smaller required size; however, high material costs have limited their implementation. To investigate the economic competitiveness of alternative magnetic materials, technical cost models (TCMs) were developed and used to examine the manufacturing economics related to the production of both NdFeB and ferrite magnets. Results from the TCMs are used to identify the cost drivers and opportunities for cost reductions. Subsequent investigations will include effects on vehicle fuel efficiency, and the environmental impact of magnet manufacture and disposal.     

智能型激光控制器提高灵活性并节省空间

激光二极管是宽带调幅光纤发射系统的核心器件。光纤系统依赖于激光的稳定性,但未受调节控制的激光二极管特性却常因制造误差、温度和使用日久所造成的参数改变而变得不稳定。因此,光纤通信系统需要专用电路来控制重要的激光二极管参数,以确保它们稳定操作。虽然激光控制电路都