The Design of Intergovernmental Equalisation Transfers: Indian States and Kosovo

Numéro de référence interne originel : a1.1 g 106

Analyse de l'exploitation des broches en UGV aéronautique

Le fraisage grande vitesse des pièces aéronautiques de grandes dimensions nécessite à la fois un taux d'enlèvement de copeaux important ainsi qu'une qualité de finition garantissant les tolérances de ces pièces à haute valeur ajoutée. Implantées sur des machines outils UGV, les électrobroches doivent supporter, sur des phases d'usinage de plusieurs heures, des sollicitations physiques importantes. Malgré les avancées technologiques, les broches apparaissent aujourd'hui comme le maillon faible des machines d'usinage à grande vitesse aéronautique. Ce papier propose un concept innovant de surveillance des broches d'UGV qui permet de suivre l'usure de celles-ci, particulièrement au niveau de leurs roulements à billes, cause principale de leurs défaillances. Pour cela des broches FISCHER ont été instrumentées de plusieurs accéléromètres, puis intégrées sur machines FOREST-LINE. Grâce aux signaux vibratoires enregistrés par un système de surveillance conçu spécifiquement et à partir d'un état de l'art sur la surveillance des roulements que nous avons réalisés, un critère vibratoire adapté au suivi de l'état des paliers des broches a été développé. De plus, les signaux et informations enregistrés lors de l'usinage par le même système de surveillance permettent de relier l'endommagement des roulements aux sollicitations subies par la broche lors de son utilisation afin d'assurer aussi une réelle surveillance du procédé en lui-même

Quiescent Saccharomyces cerevisiae forms telomere hyperclusters at the nuclear membrane vicinity through a multifaceted mechanism involving Esc1, the Sir complex, and chromatin condensation

Like other eukaryotes, Saccharomyces cerevisiae spatially organizes its chromosomes within the nucleus. In G(1) phase, the yeast’s 32 telomeres are clustered into 6–10 foci that dynamically interact with the nuclear membrane. Here we show that, when cells leave the division cycle and enter quiescence, telomeres gather into two to three hyperclusters at the nuclear membrane vicinity. This localization depends on Esc1 but not on the Ku proteins. Telomere hypercluster formation requires the Sir complex but is independent of the nuclear microtubule bundle that specifically assembles in quiescent cells. Importantly, mutants deleted for the linker histone H1 Hho1 or defective in condensin activity or affected for histone H4 Lys-16 deacetylation are impaired, at least in part, for telomere hypercluster formation in quiescence, suggesting that this process involves chromosome condensation. Finally, we establish that telomere hypercluster formation is not necessary for quiescence establishment, maintenance, and exit, raising the question of the physiological raison d’être of this nuclear reorganization

Jouez à Faire Consensus Avec MITTEN (démonstration)

National audienceCet article présente Mitten, un outil pour décrire finement et jouer des scénarios sur une implémentation de Tenderbake-le prochain protocole de consensus à la pBFT de la blockchain Tezos. Mitten est paramétrable pour filtrer et examiner les messages selon des scénarios particuliers écrits dans un DSL construit sur OCaml. Grâce à Mitten, nous avons pu écrire et simuler des scénarios subtils pour reproduire des comportements difficilement atteignables en temps normal. Nous avons également pu simuler des situations permettant d'exhiber des bugs dans l'implémentation en cours et de tester des correctifs proposés

Nonconventional localizations of cytosolic aminoacyl-tRNA synthetases in yeast and human cells

International audienceKeywords: aaRS tRNA Yeast Human Microscopy Fractionation MTS NLS a b s t r a c t By definition, cytosolic aminoacyl-tRNA synthetases (aaRSs) should be restricted to the cytosol of eukary-otic cells where they supply translating ribosomes with their aminoacyl-tRNA substrates. However, it has been shown that other translationally-active compartments like mitochondria and plastids can simultaneously contain the cytosolic aaRS and its corresponding organellar ortholog suggesting that both forms do not share the same organellar function. In addition, a fair number of cytosolic aaRSs have also been found in the nucleus of cells from several species. Hence, these supposedly cytosolic-restricted enzymes have instead the potential to be multi-localized. As expected, in all examples that were studied so far, when the cytosolic aaRS is imported inside an organelle that already contains its bona fide corresponding organellar-restricted aaRSs, the cytosolic form was proven to exert a nonconventional and essential function. Some of these essential functions include regulating homeostasis and protecting against various stresses. It thus becomes critical to assess meticulously the subcellular localization of each of these cytosolic aaRSs to unravel their additional roles. With this objective in mind, we provide here a review on what is currently known about cytosolic aaRSs multi-compartmentalization and we describe all commonly used protocols and procedures for identifying the compartments in which cytosolic aaRSs relocal-ize in yeast and human cells

A new inhibitor of the β-arrestin/AP2 endocytic complex reveals interplay between GPCR internalization and signalling.

AbstractIn addition to G protein-coupled receptor (GPCR) desensitization and endocytosis, β-arrestin recruitment to ligand-stimulated GPCRs promotes non-canonical signalling cascades. Distinguishing the respective contributions of β-arrestin recruitment to the receptor and β-arrestin-promoted endocytosis in propagating receptor signalling has been limited by the lack of selective analytical tools. Here, using a combination of virtual screening and cell-based assays, we have identified a small molecule that selectively inhibits the interaction between β-arrestin and the β2-adaptin subunit of the clathrin adaptor protein AP2 without interfering with the formation of receptor/β-arrestin complexes. This selective β-arrestin/β2-adaptin inhibitor (Barbadin) blocks agonist-promoted endocytosis of the prototypical β2-adrenergic (β2AR), V2-vasopressin (V2R) and angiotensin-II type-1 (AT1R) receptors, but does not affect β-arrestin-independent (transferrin) or AP2-independent (endothelin-A) receptor internalization. Interestingly, Barbadin fully blocks V2R-stimulated ERK1/2 activation and blunts cAMP accumulation promoted by both V2R and β2AR, supporting the concept of β-arrestin/AP2-dependent signalling for both G protein-dependent and -independent pathways.</jats:p

The experimental power of FR900359 to study Gq-regulated biological processes.

Despite the discovery of heterotrimeric αβγ G proteins ∼25 years ago, their selective perturbation by cell-permeable inhibitors remains a fundamental challenge. Here we report that the plant-derived depsipeptide FR900359 (FR) is ideally suited to this task. Using a multifaceted approach we systematically characterize FR as a selective inhibitor of Gq/11/14 over all other mammalian Gα isoforms and elaborate its molecular mechanism of action. We also use FR to investigate whether inhibition of Gq proteins is an effective post-receptor strategy to target oncogenic signalling, using melanoma as a model system. FR suppresses many of the hallmark features that are central to the malignancy of melanoma cells, thereby providing new opportunities for therapeutic intervention. Just as pertussis toxin is used extensively to probe and inhibit the signalling of Gi/o proteins, we anticipate that FR will at least be its equivalent for investigating the biological relevance of Gq

Rapid De Novo Evolution of X Chromosome Dosage Compensation in Silene latifolia, a Plant with Young Sex Chromosomes

Evidence for dosage compensation in Silene latifolia, a plant with 10-million-year-old sex chromosomes, reveals that dosage compensation can evolve rapidly in young XY systems and is not an animal-specific phenomenon

Search for dark matter produced in association with bottom or top quarks in √s = 13 TeV pp collisions with the ATLAS detector

A search for weakly interacting massive particle dark matter produced in association with bottom or top quarks is presented. Final states containing third-generation quarks and miss- ing transverse momentum are considered. The analysis uses 36.1 fb−1 of proton–proton collision data recorded by the ATLAS experiment at √s = 13 TeV in 2015 and 2016. No significant excess of events above the estimated backgrounds is observed. The results are in- terpreted in the framework of simplified models of spin-0 dark-matter mediators. For colour- neutral spin-0 mediators produced in association with top quarks and decaying into a pair of dark-matter particles, mediator masses below 50 GeV are excluded assuming a dark-matter candidate mass of 1 GeV and unitary couplings. For scalar and pseudoscalar mediators produced in association with bottom quarks, the search sets limits on the production cross- section of 300 times the predicted rate for mediators with masses between 10 and 50 GeV and assuming a dark-matter mass of 1 GeV and unitary coupling. Constraints on colour- charged scalar simplified models are also presented. Assuming a dark-matter particle mass of 35 GeV, mediator particles with mass below 1.1 TeV are excluded for couplings yielding a dark-matter relic density consistent with measurements