Next-generation sequencing of immunoglobulin gene rearrangements for clonality assessment: a technical feasibility study by EuroClonality-NGS

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Development of the initial certification and technology roadmap for the FUTPRINT50 framework

The main goal of the research project FUTPRINT50 is the acceleration of the introduction of a hybrid-electric regional aircraft. One essential part of this project is to develop a roadmap which couples the technological development with its associated research infrastructure and regulatory aspects. This aims at maximizing the likelihood of a successful hybrid-electric 50-seat regional aircraft with a projected entry-into-service by 2035/2040. This article presents the roadmap framework and methodology worked out by FUTPRINT50. Additionally, it shows the findings of the consortium about key enabling technologies and testing infrastructures necessary to achieve the final integrated demonstrators that provide evidence for lowering the risk of adoption and for bridging mapped regulatory gaps in regard to hybrid-electric propulsion. Furthermore, links to other complementary roadmaps are highlighted. Detail is given on the status of work and follow-up actions towards its completion.European Union funding: 87555

Sucres et huiles : des ingrédients clés pour la chimie biosourcée,

International audienc

Sucres et huiles : des ingrédients clés pour la chimie biosourcée,

International audienc

The tumour suppressor p53 is frequently nonfunctional in Sezary syndrome

Background: Primary cutaneous T cell lymphomas (CTCLs) are a heterogenous group with Sezary syndrome (SS) as one of its most aggressive variants. Recently, we identified a loss of E2A as a recurrent event in SS, which enhanced proliferation via up-regulation of the proto-oncogene MYC. MYC-induced transformation usually requires deleterious alterations of key apoptotic genes including p53, however p53 functionality and mutation status in SS are unclear. Objectives: We investigated functionality of p53 signaling by pharmacological treatment with the MDM2 antagonist nutlin-3, which might result in p53 activation. Furthemore, we analyzed the TP53 mutation status in CTCL cell lines and highly purified tumor cells from SS patients by mRNA and DNA sequencing. Methods: We analysed the apoptosis induction due to nutlin-3 treatment in various SS cell lines and primary patient samples by annexin V / propiumiodide staining. Induction of p53 target genes was analysed by immunoblotting and TP53 was sequenced at the mRNA and DNA level. Results: We identified various TP53 mutations and an impaired p53 signaling in the vast majority of the investigated cell lines and primary SS cells. Conclusion: In accordance with the importance of MYC deregulation in SS, p53 signaling is frequently non-functional in SS. However, although most likely ineffective as exclusive treatment in SS, it remains possible that pharmacological p53 activation could be beneficial in combination with other approaches including classical chemotherapeutics

A Bayesian approach to infer radial models of temperature and anisotropy in the transition zone from surface wave dispersion curves

International audienceMineralogical transformations and material transfers within the Earth's mantle make the 350-1000 km depth range (referred here as the mantle transition zone) highly heterogeneous and anisotropic. Most of the 3-D global tomographic models are anchored on small perturbations from 1-D models such as PREM, and are secondly interpreted in terms of temperature and composition distributions. However, the degree of heterogeneity in the transition zone can be strong enough so that the concept of a 1-D reference seismic model must be addressed. To avoid the use of any seismic reference model, we present in this paper a Markov chain Monte Carlo algorithm to directly interpret surface wave dispersion curves in terms of temperature and radial anisotropy distributions, here considering a given composition of the mantle. These interpretations are based on laboratory measurements of elastic moduli and Birch-Murnaghan equation of state. An originality of the algorithm is its ability to explore both smoothly varying models and first-order discontinuities, using C1-Bézier curves, which interpolate the randomly chosen values for depth, temperature and radial anisotropy. This parametrization is able to generate a self-adapting parameter space exploration while reducing the computing time. Thanks to a Bayesian exploration, the probability distributions on temperature and anisotropy are governed by uncertainties on the data set. The method is applied to both synthetic data and real dispersion curves. Though surface wave data are weakly sensitive to the sharpness of the of the mid-mantle seismic discontinuities, the interpretation of the temperature distribution is highly related to the chosen composition and to the modelling of mineralogical phase transformations. Surface wave measurements along the Vanuatu-California path suggest a strong anisotropy above 400 km depth, which decreases below, and a monotonous temperature distribution between 350 and 1000 km depth