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.     

Development of a Continuous Segmented Flow Tubular Reactor and the “Scale‐out” Concept – In Search of Perfect Powders

The synthesis of powders with controlled shape and narrow particle size distributions is still a major challenge for many industries. A continuous Segmented Flow Tubular Reactor (SFTR) has been developed to overcome homogeneity and scale‐up problems encountered when using batch reactors. Supersaturation is created by mixing the co‐reactants in a micromixer inducing precipitation; the suspension is then segmented into identical micro‐volumes by a non‐miscible fluid and sent through a tube. These micro‐volumes are more homogeneous when compared to large batch reactors leading to narrower size distributions, better particle morphology, polymorph selectivity and stoichiometry. All these features have been demonstrated on single tube SFTR for different chemical systems. To increase productivity for commercial application the SFTR is being “scaled‐out” by multiplying the number of tubes running in parallel instead of scaling‐up by increasing their size. The versatility of the multi‐tube unit will allow changes in type of precipitate with a minimum of new investment as new chemistry can be researched, developed and optimised in a single tube SFTR and then transferred to the multi‐tube unit for powder production.     

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)     

Vakuumgerechte Werkstoffe und Verbindungstechnik

In Part 1 (Henning, Materials used in Vacuum Technology), the application possibilities of different materials in vacuum technology were described. Part 2 describes the most important non-detachable connections of these materials to produce components that can be used in vacuum technology. The following processes are suitable for this purpose:

• ○ Welding

• ○ Soldering

• ○ Glueing

• ○ Fusion

For this reason, these four processes will be discussed in detail here; their advantages and disadvantages described and their worthiness for use in vacuum technology indicated. It should be noted here that other nondetachable connections such as rivets, point welding, projection seam welding or roll seam welding do not meet the demands of gas tightness made in vacuum technology and cannot, therefore, be used for such purposes.     

On enabling integrated process compliance with semantic constraints in process management systems

Key to broad use of process management systems (PrMS) in practice is their ability to foster and ease the implementation, execution, monitoring, and adaptation of business processes while still being able to ensure robust and error-free process enactment. To meet these demands a variety of mechanisms has been developed to prevent errors at the structural level (e.g., deadlocks). In many application domains, however, processes often have to comply with business level rules and policies (i.e., semantic constraints) as well. Hence, to ensure error-free executions at the semantic level, PrMS need certain control mechanisms for validating and ensuring the compliance with semantic constraints. In this paper, we discuss fundamental requirements for a comprehensive support of semantic constraints in PrMS. Moreover, we provide a survey on existing approaches and discuss to what extent they are able to meet the requirements and which challenges still have to be tackled. In order to tackle the particular challenge of providing integrated compliance support over the process lifecycle, we introduce the SeaFlows framework. The framework introduces a behavioural level view on processes which serves a conceptual process representation for constraint specification approaches. Further, it provides general compliance criteria for static compliance validation but also for dealing with process changes. Altogether, the SeaFlows framework can serve as formal basis for realizing integrated support of semantic constraints in PrMS.