Role of p52 (NF-κB2) in LPS tolerance in a human B cell line

Cells of the weakly CD14 positive human B cell line RPMI 8226, clone 1, will mobilize NF-κB (p50/p65 and p50/p50) proteins and produce TNF mRNA when stimulated with lipopolysaccharide (LPS), When such cells are precultured with a low amount of LPS (50 - 250 ng/ml) for 3 - 4 days followed by a secondary stimulation with a high dose of LPS (1 mu g/ml) then the cytokine expression is strongly reduced, i.e, the cells have become tolerant. Western blot analysis of proteins of the NF-kappa B/rel family demonstrates cytoplasmic p50 and p65 for naive B cells plus a low level of p52. While with tolerance induction the pattern of p50 and p65 proteins remains essentially unchanged, the LPS tolerant 8226 cells show a dramatic increase of both p52 protein and its p100 precursor in the cytosol. This p52 is found strongly upregulated in Western blots of extracts from purified nuclei of tolerant cells, Also, gelshift analysis with the -605 kappa B motif Of the human TNF 5'-region shows an additional high mobility complex in LPS tolerant cells - a complex that is supershifted with an anti-p52 antibody, Functional analysis with the -1064 TNF 5'-region in front of the luciferase reporter gene demonstrates that transactivation of the TNF promoter is strongly reduced in tolerant cells, Also, overexpression of p52 will suppress activity of TNF promoter reporter gene constructs. Taken together these data show that tolerance to LPS in the human RPM1 8226 a cell line involves upregulation of the p52 (NF-kappa B2) gene, which appears to be instrumental in the blockade of TNF gene expression

Evidence-based teacher education and correlation analyses

Die Lehrkräftebildung verwendet das wissenschaftliche Konstrukt der Evidenz als Grundlage von Entscheidungsprozessen in der Gestaltung von Lerngelegenheiten zu inklusivem Unterrichten. Zwar ist der Zusammenhang von Diagnosewissen und positiver Einstellung zu inklusivem Unterrichten anerkannt, die dazu verfügbare quantitative Evidenz unterliegt jedoch zahlreichen Einschränkungen. Wir diskutieren die Bedingungen der Herstellung von Evidenz in der Lehrkräftebildung und zeigen im Kontext von Zusammenhangsanalysen typische Fehlerquellen klassischer Berechnungsverfahren auf. Datengrundlage ist eine quasi-experimentelle Studie mit 63 Lehramtsstudierenden, die problemorientiert oder instruktionsbasiert pädagogisches Diagnostizieren lernen. Durch die Anwendung eines innovativen statistischen Verfahrens, mit dem manifeste Wachstumskurvenmodelle in kleinen Stichproben berechnet werden können, zeigen wir, dass ein Zuwachs an Diagnosewissen mit einer Steigerung positiver Einstellungen zu inklusivem Unterrichten einhergehen kann. Im Anschluss diskutieren wir die Bedeutung der Ergebnisse für den Übergang angehender Lehrkräfte in die Schulpraxis.Teacher education utilizes the scientific construct of evidence for decisions on the design of teacher trainings. While the relationship between diagnostic knowledge and positive attitudes towards inclusive teaching is widely accepted, the available evidence is constrained by many factors. We discuss the conditions of constructing evidence in teacher education and show typical errors of classical correlation analyses. Our analyses are based on a quasi-experimental study with 63 pre-service teachers, who learned how to diagnose students either with problem-based learning or with instruction-based learning. Applying an innovative statistical method that allows for calculating growth-curve models with small sample sizes, we show that a growth in diagnostic knowledge can correlate with a growth in positive attitudes towards inclusive teaching. In the discussion we focus on the meaning of the results for the transition of pre-service teachers into teaching

Me, My Girls, and the Ideal Hotel: Segmenting Motivations of the Girlfriend Getaway Market Using Fuzzy C-Medoids for Fuzzy Data.

Segmenting the motivation of travelers using the push and pull framework remains ubiquitous in tourism. This study segments the girlfriend getaway (GGA) market on motivation (push) and accommodation (pull) attributes and identifies relationships between these factors. Using a relatively novel clustering algorithm, the Fuzzy C-Medoids clustering for fuzzy data (FCM-FD), on a sample of 749 women travelers, three segments (Socializers, Enjoyers, and Rejoicers) are uncovered. The results of a multinomial fractional model show relationships between the clusters of motivation and accommodation attributes as well as sociodemographic characteristics. The research highlights the importance of using a gendered perspective in applying well established motivation models such as the push and pull framework. The findings have implications for both destination and accommodation management

Apixaban for Extended Treatment of Venous Thromboembolism

BACKGROUND Apixaban, an oral factor Xa inhibitor that can be administered in a simple, fixed-dose regimen, may be an option for the extended treatment of venous thromboembolism. METHODS In this randomized, double-blind study, we compared two doses of apixaban (2.5 mg and 5 mg, twice daily) with placebo in patients with venous thromboembolism who had completed 6 to 12 months of anticoagulation therapy and for whom there was clinical equipoise regarding the continuation or cessation of anticoagulation therapy. The study drugs were administered for 12 months. RESULTS A total of 2486 patients underwent randomization, of whom 2482 were included in the intention-to-treat analyses. Symptomatic recurrent venous thromboembolism or death from venous thromboembolism occurred in 73 of the 829 patients (8.8%) who were receiving placebo, as compared with 14 of the 840 patients (1.7%) who were receiving 2.5 mg of apixaban (a difference of 7.2 percentage points; 95% confidence interval [CI], 5.0 to 9.3) and 14 of the 813 patients (1.7%) who were receiving 5 mg of apixaban (a difference of 7.0 percentage points; 95% CI, 4.9 to 9.1) (P <0.001 for both comparisons). The rates of major bleeding were 0.5% in the placebo group, 0.2% in the 2.5-mg apixaban group, and 0.1% in the 5-mg apixaban group. The rates of clinically relevant nonmajor bleeding were 2.3% in the placebo group, 3.0% in the 2.5-mg apixaban group, and 4.2% in the 5-mg apixaban group. The rate of death from any cause was 1.7% in the placebo group, as compared with 0.8% in the 2.5-mg apixaban group and 0.5% in the 5-mg apixaban group. CONCLUSIONS Extended anticoagulation with apixaban at either a treatment dose (5 mg) or a thromboprophylactic dose (2.5 mg) reduced the risk of recurrent venous thromboembolism without increasing the rate of major bleeding. (Funded by Bristol-Myers Squibb and Pfizer; AMPLIFY-EXT ClinicalTrials.gov number, NCT00633893.