ULK1 inhibition overcomes compromised antigen presentation and restores antitumor immunity in LKB1-mutant lung cancer

Inactivating mutations in LKB1/STK11 are present in roughly 20% of nonsmall cell lung cancers (NSCLC) and portend poor response to anti-PD-1 immunotherapy. Unexpectedly, we found that LKB1 deficiency correlated with elevated tumor mutational burden (TMB) in NSCLCs from nonsmokers and genetically engineered mouse models, despite the frequent association between high-TMB and anti-PD-1 treatment efficacy. However, LKB1 deficiency also suppressed antigen processing and presentation, which are associated with compromised immunoproteasome activity and increased autophagic flux. Immunoproteasome activity and antigen presentation were restored by inhibiting autophagy through targeting the ATG1/ULK1 pathway. Accordingly, ULK1 inhibition synergized with PD-1 antibody blockade, provoking effector T-cell expansion and tumor regression in Lkb1-mutant tumor models. This study reveals an interplay between the immunoproteasome and autophagic catabolism in antigen processing and immune recognition, and proposes the therapeutic potential of dual ULK1 and PD-1 inhibition in LKB1-mutant NSCLC as a strategy to enhance antigen presentation and to promote antitumor immunity

Social Media, Gender and the Mediatisation of War: Exploring the German Armed Forces’ Visual Representation of the Afghanistan Operation on Facebook

Studies on the mediatisation of war point to attempts of governments to regulate the visual perspective of their involvements in armed conflict – the most notable example being the practice of ‘embedded reporting’ in Iraq and Afghanistan. This paper focuses on a different strategy of visual meaning-making, namely, the publication of images on social media by armed forces themselves. Specifically, we argue that the mediatisation of war literature could profit from an increased engagement with feminist research, both within Critical Security/Critical Military Studies and within Science and Technology Studies that highlight the close connection between masculinity, technology and control. The article examines the German military mission in Afghanistan as represented on the German armed forces’ official Facebook page. Germany constitutes an interesting, and largely neglected, case for the growing literature on the mediatisation of war: its strong antimilitarist political culture makes the representation of war particularly delicate. The paper examines specific representational patterns of Germany’s involvement in Afghanistan and discusses the implications which arise from what is placed inside the frame of visibility and what remains out of its view

Time activity modelling of domestic exposures to radon

Radon gas occurs naturally in the environment with a variable distribution. In some areas radon concentrates sufficiently within the built environment that it is considered as a public health risk. It is possible, successfully, to reduce radon levels in the built environment, and it has been shown that such remediation programmes can be justified in terms of the costs and benefits accruing. However, the estimated dose received by people in their homes depends on the time spent indoors. The research presented here uses data derived from time activity surveys in Northamptonshire, together with radon data from a representative home, to model potential exposures for different population sub-groups. Average home occupancy ranged from 14.8 h (probable error 2.5 h) for students to 17.7 (3.1) h for adults; schoolchildren spent an average of 14.9 (1.2) h at home. Over a quarter of adults, however, were in the home for 22 h on more. These differences in occupancy patterns lead to substantial differences in radon exposure. In a home with an average hourly ground floor radon concentration of 467 Bq m−3, modelled hourly average exposures ranged from ca. 250 Bq m−3 for students and school children, to over 340 Bq m−3, for women based at home. Modelled exposures show a non-linear association with total time spent at home, suggesting that exposure estimates based on linear models may provide misleading estimates of health risks from radon and the potential benefits of radon remediation. Highest hourly exposures are likely to be experienced by people with highly occupancy, living in single-storey, ground floor accommodation (for example, the elderly the infirm and non-working young mothers). Since these may be least aware of radon risks, and least able to take up remediation measures, they should be specifically targeted for radon monitoring and for assistance in remediation scheme

The Age-ility Project (Phase 1): Structural and functional imaging and electrophysiological data repository

Our understanding of the complex interplay between structural and functional organisation of brain networks is being advanced by the development of novel multi-modal analyses approaches. The Age-ility Project (Phase 1) data repository offers open access to structural MRI, diffusion MRI, and resting-state fMRI scans, as well as resting-state EEG recorded from the same community participants (n=131, 15-35y, 66 male). Raw imaging and electrophysiological data as well as essential demographics are made available via the NITRC website. All data have been reviewed for artifacts using a rigorous quality control protocol and detailed case notes are provided