miR-181a is a novel player in the STAT3-mediated survival network of TCRαβ+ CD8+ T large granular lymphocyte leukemia

T-LGL cells arise as a consequence of chronic antigenic stimulation and inflammation and thrive because of constitutive activation of the STAT3 and ERK pathway. Notably, in 40% of patients, constitutive STAT3 activation is due to STAT3 activating mutations, whereas in 60% this is unknown. As miRNAs are amongst the most potent regulators in health and disease, we hypothesized that aberrant miRNA expression could contribute to dysregulation of these pathways. miRNA sequencing in T-LGL leukemia cases and aged-matched healthy control TEMRA cells revealed overexpression of miR-181a. Furthermore, geneset enrichment analysis (GSEA) of downregulated targets of miR-181a implicated involvement in regulating STAT3 and ERK1/2 pathways. Flow cytometric analyses showed increased SOCS3+ and DUSP6+ T-LGL cells upon miR-181a inhibition. In addition, miR-181a-transfected human CD8+ T cells showed increased basal STAT3 and ERK1/2 phosphorylation. By using TL1, a human T-LGL cell line, we could show that miR-181a is an actor in T-LGL leukemia, driving STAT3 activation by SOCS3 inhibition and ERK1/2 phosphorylation by DUSP6 inhibition and verified this mechanism in an independent cell line. In addition, miR-181a inhibition resulted in a higher sensitivity to FAS-mediated apoptosis. Collectively, our data show that miR-181a could be the missing link to explain why STAT3-unmutated patients show hyperactive STAT3

If You Could Only Choose Five Psychotropic Medicines: Updating the Interagency Emergency Health Kit

Mark van Ommeren and colleagues describe how they chose five psychotropic medicines to add to the Interagency Emergency Health Kit, which is a box with medicines and medical supplies designed to help people in major humanitarian emergencies

Metaphor and intertextuality in media framings of the (1984-85) British Miners' Strike:a multimodal analysis

The British Miners’ Strike of 1984-1985 represents one of the most pivotal periods in British industrial relations. Media stance toward the miners remains a controversial issue today, as attested by recent publications looking back at the strike (Williams 2009a, 2014). Here, authors including miners, journalists and other commentators argue that media coverage of the strike followed a consistently anti trade union agenda in which the media sought to destabilise the strike. An internal BBC report only recently made public shows that the BBC themselves had concerns over possible imbalances in their coverage of the so-called ‘Battle of Orgreave’ (Harcup 2014). Despite the weight attached to media coverage in this context, however, surprisingly little research has been conducted from a discourse-analytical perspective to show systematically and empirically how such an agenda may have been manifested across media texts. In this paper, drawing on Critical Cognitive Linguistics, I show how one particular metaphorical framing of the strike, which construed the strike as a war between the State and the National Union of Miners, persisted through the year long period and consider the potential ideological functions of this framing in media strategies of (de)legitimation. I show how this metaphor featured in linguistic, visual and multimodal forms of media representatio

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Track E Implementation Science, Health Systems and Economics

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138412/1/jia218443.pd

Testing policy options for Horizon 2020 with SKIN

This chapter is about a SKIN application to the world of EU-funded research networks in the area of information and communication technologies (ICT). The application was commissioned by the DG Information Society and Media (DG INFSO) as an impact assessment of the funding strategies in the 7th Framework Programme (FP7) and ex-ante evaluation of the upcoming funding cycle called Horizon 2020. The focus of this chapter is on the changes of the SKIN model to become SKIN-INFSO, the strategy to calibrate the adapted SKIN model with empirical data from the European Commission to achieve realistic simulation results, and the ways we analysed and validated our results using network analysis. Details of the policy experiments using the SKIN-INFSO application for the study and their results are reported elsewhere [Ahrweiler, Gilbert, Pyka, Innovation policy modelling with SKIN. In: Johnston E et al (eds) Policy informatics. MIT Press, Cambridge, 2014, forthcoming]. © 2014 Springer-Verlag Berlin Heidelberg

Testing policy options for Horizon 2020 with SKIN

This chapter is about a SKIN application to the world of EU-funded research networks in the area of information and communication technologies (ICT). The application was commissioned by the DG Information Society and Media (DG INFSO) as an impact assessment of the funding strategies in the 7th Framework Programme (FP7) and ex-ante evaluation of the upcoming funding cycle called Horizon 2020. The focus of this chapter is on the changes of the SKIN model to become SKIN-INFSO, the strategy to calibrate the adapted SKIN model with empirical data from the European Commission to achieve realistic simulation results, and the ways we analysed and validated our results using network analysis. Details of the policy experiments using the SKIN-INFSO application for the study and their results are reported elsewhere [Ahrweiler, Gilbert, Pyka, Innovation policy modelling with SKIN. In: Johnston E et al (eds) Policy informatics. MIT Press, Cambridge, 2014, forthcoming]. © 2014 Springer-Verlag Berlin Heidelberg