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.     

The evolution of government housing policy: The case of new south Wales 1901–41

This paper sets out the development of four main threads of housing policy in New South Wales from the latter part of the 19th century through the first 40 years of the 20th century. Following a discussion of the social and political circumstances and debate surrounding government policy regarding landlord/tenant relations, housing quality and supply, and owner occupancy, it concludes that policy evolution is irregular and a product of the exigencies of the political process. It also suggests that although government policy did little to improve the housing situation for the underprivileged, there was nevertheless a growing acceptance by both Labor and conservative parties of the increased need for government intervention in the housing market.     

Cellular automata model of gravity-driven granular flows

A cellular automata model is used to simulate a variety of granular chute flows. The model is tested against several case studies: flow down a chute, flow past an obstacle, chute flow in which complex, counter-rotating vortices result in streamwise surface stripes and flow near a boundary. The model successfully reproduces experimental observations in all of these cases. These results lead us to propose that simple, rule-based, models such as this can improve our detailed understanding of dynamics and flow within an opaque granular bed.     

Workstation redesign for a repetitive drill press operation: A combined work design and ergonomics approach

A typical or conventional workstation for a repetitive drill press operation was evaluated and subsequently redesigned by incorporating the concepts and principles of work design and ergonomics. The production task comprised of drilling four holes on a prepared steel plate. A methods–time measurement (MTM) analysis was conducted to eliminate unnecessary motions and improve the necessary (work) motions involved in task performance. The specific features of the redesigned workstation were specially designed equipment (jig, fixture, etc.), a suitable adjustable chair, proper work height, a placement of tools/equipment within reach envelope, and a comprehensive operator training method. An experimental investigation was conducted to evaluate and test the redesigned workstation in terms of operator productivity (production quantity and quality output) and satisfaction. The increases in quantity (number of holes drilled) and quality (number of good holes drilled) output were 22 and 50%, respectively, for the redesigned workstation compared to the typical or conventional workstation. The high improvement in quality output (50%) could be attributed to the improved design of the jig and fixture and the comprehensive operator training method, which emphasizes the quality aspect of production output. The improvement in operator satisfaction (scores) were highly significant. This investigation has demonstrated the beneficial effect of a combined work design and ergonomics approach, especially for the redesign of a workstation for a repetitive drill press operation. © 2007 Wiley Periodicals, Inc. Hum Factors Man 17: 395–410, 2007.     

Adaptive flexibility and maladaptive routines in selecting fast and frugal decision strategies.

Decision routines unburden the cognitive capacity of the decision maker. In changing environments, however, routines may become maladaptive. In 2 experiments with a hypothetical stock market game (n = 241), the authors tested whether decision routines tend to persist at the level of decision strategies rather than at the level of options in strategy selection. The payoff structure of the task was changed after 80 decision trials, rendering a new strategy optimal with respect to expected payoff. Whereas most participants detected the appropriate strategy at the beginning of the task, they tended to retain it even when it was no longer optimal. A hint about a possible change had only a small influence on this maladaptive routine; a monetary incentive had none. Switching to a similar but not identical task relaxed the routine, but not much. (PsycINFO Database Record (c) 2010 APA, all rights reserved)