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.     

General properties of antennas

In antenna design there are some fundamental relationships based on reciprocity. The equivalence of antenna pattern in transmission and reception is well known. Less well known is the time-derivative relationship going from reception to transmission. These relationships are derived here and expressed in various useful forms. Electric and magnetic dipoles are given special consideration, and the combined form constructed as a terminated TEM transmission line (the BTW antenna) is discussed for its transmission and reception properties     

Methods for packet combining in HARQ systems over bursty channels

The performance of ARQ systems can be improved by combining current and prior transmissions at the receiver. Two techniques for combining outputs in a packet-based communication system are presented. In both techniques the fundamental unit of retransmission is a packet, and the fundamental unit of combining is a codeword. The techniques are analyzed for a bursty channel and a system that employs Reed–Solomon coding and bounded-distance errors-and-erasures decoding. Performance results show that the packet-combining schemes provide significant gains in throughput and reductions in error probability when compared with a system that does not employ combining. This revised version was published online in June 2006 with corrections to the Cover Date.     

Breath and blood ethanol following use of a cough-cold preparation

All leaders in health care today are charged with the responsibility of transforming present practices into new and different ones that are needed for the future. The structural side of transforming is ultimately easier than the human side. However, the most frequent failures come from not concentrating sufficiently on the behavioral side of the change. Structural and psychological change must occur simultaneously and embrace each other for best results.     

Comparison between the effects of positive noncatastrophic HBM ESDstress in n-channel and p-channel power MOSFETs

The effect of noncatastrophic positive human body model (HBM) electrostatic discharge (ESD) stress on n-channel power MOSFETs is radically different from that on p-channel MOSFETs. In n-channel transistors, the stress causes negative shifts of the current-voltage characteristics indicative of positive charge trapping in the gate oxide. In p-channel transistors, the stress increases the drain-to-source leakage current, probably due to localized avalanche electron injection from the p-doped drain     

Bayesian generation of dependent erasures for frequency-hopcommunications and fading channels

The use of block coding and errors-and-erasures decoding can enhance performance in frequency-hop (FH) communication systems, provided that a good scheme is employed to determine which symbols to erase. The problem of making erasure decisions from collections of receiver outputs is investigated in this paper. Methods to determine which received symbols to erase are derived from Bayesian decision theory. Decision rules are developed for a system with M-ary orthogonal signaling, noncoherent demodulation, and frequency-selective fading. One result is a class of Bayesian schemes in which erasure decisions are made independently from symbol to symbol. Within this class is a rule that uses signal amplitude estimates for improved performance. A second result is a Bayesian technique in which erasure decisions are mutually dependent and are made collectively for each codeword. These techniques are analyzed and compared with the performance of receivers that use erasure techniques that require multiple applications of bounded distance decoding. The performance of the Bayesian techniques for dependent erasures are also compared with the performance of receivers that do not permit erasures. It is found that each of the Bayesian techniques offers substantial performance gains over errors-only decoding, and the dependent erasure scheme provides the best performance among the techniques of lower complexity     

Real-time NMR investigations of triple-helix folding and collagen folding diseases

Folding of the collagen triple helix provides an opportunity to look at multichain molecular assembly. This triple helix also offers unique advantages for the study of folding because the process is very slow compared to globular proteins, and the kinetics of folding can be obtained in real time by NMR. Studies on triple-helical peptides illustrate the ability to observe kinetic folding intermediates directly and the ability to propose detailed mechanisms of folding through the use of real-time NMR methods. Defective collagen folding has been implicated in various connective tissue diseases and the capacity of NMR to look at the folding of specific sites provides a tool for obtaining information about altered folding mechanisms. Comparison of folding in peptides that model normal and diseased collagens could shed light on the molecular perturbation and the etiology of disease.