In Vivo Functional Platform Targeting Patient-Derived Xenografts Identifies WDR5-Myc Association as a Critical Determinant of Pancreatic Cancer

SummaryCurrent treatment regimens for pancreatic ductal adenocarcinoma (PDAC) yield poor 5-year survival, emphasizing the critical need to identify druggable targets essential for PDAC maintenance. We developed an unbiased and in vivo target discovery approach to identify molecular vulnerabilities in low-passage and patient-derived PDAC xenografts or genetically engineered mouse model-derived allografts. Focusing on epigenetic regulators, we identified WDR5, a core member of the COMPASS histone H3 Lys4 (H3K4) MLL (1–4) methyltransferase complex, as a top tumor maintenance hit required across multiple human and mouse tumors. Mechanistically, WDR5 functions to sustain proper execution of DNA replication in PDAC cells, as previously suggested by replication stress studies involving MLL1, and c-Myc, also found to interact with WDR5. We indeed demonstrate that interaction with c-Myc is critical for this function. By showing that ATR inhibition mimicked the effects of WDR5 suppression, these data provide rationale to test ATR and WDR5 inhibitors for activity in this disease

Proceedings of the Fifth Italian Conference on Computational Linguistics CLiC-it 2018

On behalf of the Program Committee, a very warm welcome to the Fifth Italian Conference on Computational Linguistics (CLiC-­‐it 2018). This edition of the conference is held in Torino. The conference is locally organised by the University of Torino and hosted into its prestigious main lecture hall “Cavallerizza Reale”. The CLiC-­‐it conference series is an initiative of the Italian Association for Computational Linguistics (AILC) which, after five years of activity, has clearly established itself as the premier national forum for research and development in the fields of Computational Linguistics and Natural Language Processing, where leading researchers and practitioners from academia and industry meet to share their research results, experiences, and challenges

Chapitre 4. Le décalage entre attitudes et comportements en matière de protection de l'environnement

Le texte qui suit s’appuie essentiellement sur une enquête menée en 1997 auprès de salariés d’entreprises industrielles françaises engagées dans la voie de la gestion environnementale. Il se situe dans le cadre des recherches conduites en France sur la construction sociale de l’environnement et, notamment, celles visant à démontrer qu’il n’existe pas « une nature » unique pour tout le monde, qui ne soit pas d’abord vécue et pratiquée, en d’autres termes, médiatisée par l’expérience (Lascoumes..

The social construction of a health controversy. The case of electricity smart meters in France

International audienceThis article presents a sociological study of the public controversy over electricity smart meters in France. It asks how this controversy has emerged nationally and how, rather than waning as a result of expertise produced to dispel uncertainty, it has instead grown stronger. Drawing on an in-depth cross-analysis of the French press published over the period 2015-2016 and a heterogeneous corpus of documents (expert reports, approach papers, etc.), the study highlights the public, multidimensional, and health-focused nature of the controversy, as well as its origin from scares imported from abroad. Above all, it reveals how this controversy extends beyond discussion of the intrinsic qualities of the technical object itself (the smart meter) to fuel reflection on the anti-democratic dimension of the rollout projet