Predicting EQ-5D index scores from Promis Profile 29 in the United Kingdom, France, And Germany

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recor

TNFR1 and TNFR2 regulate the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms

The huge majority of myeloma cell lines express TNFR2 while a substantial subset of them failed to show TNFR1 expression. Stimulation of TNFR1 in the TNFR1-expressing subset of MM cell lines had no or only a very mild effect on cellular viability. Surprisingly, however, TNF stimulation enhanced cell death induction by CD95L and attenuated the apoptotic effect of TRAIL. The contrasting regulation of TRAIL- and CD95L-induced cell death by TNF could be traced back to the concomitant NFκB-mediated upregulation of CD95 and the antiapoptotic FLIP protein. It appeared that CD95 induction, due to its strength, overcompensated a rather moderate upregulation of FLIP so that the net effect of TNF-induced NFκB activation in the context of CD95 signaling is pro-apoptotic. TRAIL-induced cell death, however, was antagonized in response to TNF because in this context only the induction of FLIP is relevant. Stimulation of TNFR2 in myeloma cells leads to TRAF2 depletion. In line with this, we observed cell death induction in TNFR1-TNFR2-costimulated JJN3 cells. Our studies revealed that the TNF-TNF receptor system adjusts the responsiveness of the extrinsic apoptotic pathway in myeloma cells by multiple mechanisms that generate a highly context-dependent net effect on myeloma cell survival

Students academic profiles as a measure of the accuracy of school transition decisions: A validation study

In verschiedenen europäischen Ländern führt der Wechsel zur Sekundarschule zu einer bedeutsamen Aufgliederung der Bildungswege, welche ein unterschiedlich hohes Schulleistungsniveau der Schüler*innen voraussetzen. Die Akkuratheit der Zuweisung von Sekundarschulformen bestimmt nicht nur die Optionen der Schüler*innen bei späteren Übergangen im Bildungssystem, sondern beeinflusst auch den weiteren beruflichen und persönlichen Werdegang der Schüler*innen. Schüler*innen mit Migrationshintergrund sind auf die höheren sekundären Schulformen unterrepräsentiert. Inwiefern diese Unterrepräsentation auf stereotypgeprägte Leistungserwartungen zurückzuführen ist, ist bis jetzt unklar, denn es lisgt kein Kriterium vor, um die Urteilsakkuratheit adäquat zu messen. In diesem Kapitel wird ein Ansatz beschrieben, ein solches Akkuratheitskriterium zu entwickeln und zu validieren. In einem zweiten Schritt wird das Kriterium angewendet, um den Zusammenhang zwischen stereotypgeprägten Erwartungen und der Akkuratheit der Übergangsentscheidungen zu untersuchen. Das Kriterium erweist sich als valides Maß und könnte so einen wertvollen Ansatz für weitere Untersuchungen der Akkuratheit von Lehrerurteilen darstellen. Obwohl Lehrer*innen im Allgemeinen eine hohe Urteilsakkuratheit aufweisen, bestätigen die Befunde dennoch die Zusammenhänge zwischen stereotypgeprägten Erwartungen und Urteilsverzerrungen

Polylox barcoding reveals haematopoietic stem cell fates realized in vivo

Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system. Polylox recombination in situ reaches a practical diversity of several hundred thousand barcodes, allowing tagging of single cells. We have used this experimental system, combined with fate mapping, to assess haematopoietic stem cell (HSC) fates in vivo. Classical models of haematopoietic lineage specification assume a tree with few major branches. More recently, driven in part by the development of more efficient single-cell assays and improved transplantation efficiencies, different models have been proposed, in which unilineage priming may occur in mice and humans at the level of HSCs. We have introduced barcodes into HSC progenitors in embryonic mice, and found that the adult HSC compartment is a mosaic of embryo-derived HSC clones, some of which are unexpectedly large. Most HSC clones gave rise to multilineage or oligolineage fates, arguing against unilineage priming, and suggesting coherent usage of the potential of cells in a clone. The spreading of barcodes, both after induction in embryos and in adult mice, revealed a basic split between common myeloid-erythroid development and common lymphocyte development, supporting the long-held but contested view of a tree-like haematopoietic structure

B cell lymphoma in hiv transgenic mice

none9noneSabrina Curreli;Selvi Krishnan;Marvin Reitz;Yanto Lunardi-Iskandar;Mark K Lafferty;Alfredo Garzino-Demo;Davide Zella;Robert C Gallo;Joseph BryantSabrina, Curreli; Selvi, Krishnan; Marvin, Reitz; Yanto Lunardi, Iskandar; Mark K., Lafferty; GARZINO DEMO, Alfredo; Davide, Zella; Robert C., Gallo; Joseph, Bryan