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.     

Nursing and the New Deal: we met the challenge

The years of the great depression were marked with unemployment and economic ruin for many people. Americans were left feeling helpless and hopeless. After the 1932 presidential election of Franklin Roosevelt, his administration embarked on a course of government known as the New Deal. Many new and innovative programs were established to create jobs and a sense of hope for the public. This article will examine four programs that were of particular interest to nursing: the Federal Emergency Relief Act, the Civil Works Act, the Works Progress Act, and the Social Security Act. Nurses of the time embraced these programs. They participated in their development and implementation and made a difference in the lives of many desperate Americans.     

Computer-aided analysis of free-running microwave oscillators

The authors present a newly developed free-running steady-state oscillator analysis algorithm suited to large-signal oscillator analysis. Kurokawa's oscillation condition is coupled with the modified nodal admittance form of the circuit equations to avoid degenerate solutions. The algorithm was implemented by using both harmonic balance and frequency-domain spectral balance techniques. It was used in the simulation of monolithically integrated varactor-tuned MESFET oscillator. Good agreement between simulated power and oscillation frequency results was obtained     

THE LINEAR NORMALIZATION TECHNIQUE—AN ALTERNATIVE PROCEDURE FOR DETERMINING J-R CURVES FROM A SINGLE SPECIMEN TEST RECORD BASED ON LANDES' NORMALIZATION METHOD

An alternative approach for determining J-R curves from a single specimen test based on the normalization technique is proposed. The procedure requires only the load versus load-line displacement record and the final crack length in order to derive the J-R curve. The method has been applied to metal and polymers of various geometries and was verified by comparison with J-R curves obtained from potential drop and multiple specimen techniques.     

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)