SPIRAL 2 coupler preparation and RF conditioning

Proc. On LineInternational audienceFive radiofrequency coupler prototypes have been manufactured. Three of them will be mounted in the cryomodules of the SPIRAL 2 superconducting LINAC (LINear ACcelerator). This paper describes the coupler preparation and the first results of their conditioning

Planck pre-launch status : The Planck mission

Peer reviewe

Medições de nêutrons oriundos de radiação cósmica em Puno (Peru)

International audienceuma participação no projeto HARMLESS, Atividades de Pesquisa e Desenvolviment

In Flight SEU/MCU Sensitivity of Commercial Nanometric SRAMs: Operational Estimations

International audienceA method and the corresponding platform devoted to operational SEE-rate prediction are presented and illustrated by experimental results. Predicted error-rates are in well agreement with results issued from the activation of an SRAM platform, in 90 nm technology node, on board stratospheric balloons flights. Direct ionization of protons is investigated for a 65 SRAM memory virtually boarded on the balloon flight

Continuous High-Altitude Measurements of Cosmic Ray Neutrons and SEU/MCU at Various Locations: Correlation and Analyses Based-On MUSCA SEP

International audienceIn this paper are described measurements at high-altitude of both radiation environment and effects. These measurements comprise cosmic ray neutrons and SBU/MCU on nanoscales devices. Results obtained at Pic-du-Midi, France, and in the city of Puno, Peru, are presented and analyzed. Analyses and cross comparisons based-on MUSCA SEP3 calculations show a good agreement between experimental data and modeling, thus illustrating the importance of the knowledge of the radiation field for a reliable prediction

Continuous high-altitude measurements of cosmic ray neutrons and SEU/MCU at various locations: correlation and analyses based on MUSCA SEP3

International audienceIn this paper are described measurements at high-altitude of both radiation environment and effects. These measurements integrate cosmic ray neutrons and SEU/MCU on nano-scales devices. Correlation and analyses based-on MUSCA SEP3 are performed

Streptogramin A derivatives as mitochondrial translation inhibitors to suppress glioblastoma stem cell growth

New therapeutic strategies for glioblastoma treatment, especially tackling the tumour's glioblastoma stem cell (GSC) component, are an urgent medical need. Recently, mitochondrial translation inhibition has been shown to affect GSC growth, clonogenicity, and self-renewal capability, therefore becoming an attractive therapeutic target. The combination of streptogramins B and A antibiotics quinupristin/dalfopristin (Q/D), which inhibits mitochondrial ribosome function, affects GSCs more effectively in vitro than the standard of care temozolomide. Here, docking calculations based on the cryo-EM structure of the Q/D-bound mitochondrial ribosome have been used to develop a series of streptogramin A derivatives. We obtained twenty-two new and known molecules starting from the dalfopristin and virginiamycin M1 scaffolds. A structure-activity relationship refinement was performed to evaluate the capability of these compounds to suppress GSC growth and inhibit mitochondrial translation, either alone or in combination with quinupristin. Finally, quantitative ultra HPLC-mass spectrometry allowed us to assess the cell penetration of some of these derivatives. Among all, the fluorine derivatives of dalfopristin and virginiamycin M1, (16R)-1e and (16R)-2e, respectively, and flopristin resulted in being more potent than the corresponding lead compounds and penetrating to a greater extent into the cells. We, therefore, propose these three compounds for further evaluation in vivo as antineoplastic agents

A high-content screening of anti-cancer compounds suggests the multiple tyrosine kinase inhibitor ponatinib for repurposing in neuroblastoma therapy.

Novel druggable targets have been discovered in neuroblastoma (NB), paving the way for more effective treatments. However, children with high-risk NB still show high mortality rates prompting for a search of novel therapeutic options. Here, we aimed at repurposing FDA-approved drugs for NB treatment by performing a high-content screening of a 349 anticancer compounds library. In the primary screening, we employed three NB cell lines, grown as three-dimensional (3D) multicellular spheroids, which were treated with 10 \u3bcmol/L of the library compounds for 72 hours. The viability of 3D spheroids was evaluated using a high-content imaging approach, resulting in a primary hit list of 193 compounds. We selected 60 FDA-approved molecules and prioritized drugs with multi-target activity, discarding those already in use for NB treatment or enrolled in NB clinical trials. Hence, 20 drugs were further tested for their efficacy in inhibiting NB cell viability, both in two-dimensional and 3D models. Dose-response curves were then supplemented with the data on side effects, therapeutic index, and molecular targets, suggesting two multiple tyrosine kinase inhibitors, ponatinib and axitinib, as promising candidates for repositioning in NB. Indeed, both drugs showed induction of cell-cycle block and apoptosis, as well as inhibition of colony formation. However, only ponatinib consistently affected migration and inhibited invasion of NB cells. Finally, ponatinib also proved effective inhibition of tumor growth in orthotopic NB mice, providing the rationale for its repurposing in NB therap