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Assessing the ship motion prediction capabilities of the open-source model NEMOH against field observations
No full textInternational audienc
Ultramafic float rocks at Jezero crater (Mars): excavation of lower crustal rocks or mantle peridotites by impact cratering?
No full textInternational audienceBased on observation and data from meteorites and in situ scientific missions, experiments as well as models, the Martian mantle is assumed to share some compositional and mineralogical affinity with the terrestrial mantle. However, there might be subtle differences like the Martian mantle being more ferroan. Yet, we do not have any direct analysis of a Martian mantle rock to confirm this assumption. NASA’s Perseverance rover found olivine-rich boulder-sized float rocks on the upper Jezero fan (Mars). These boulders have an ultramafic composition and their mineralogy is dominantly composed of Fo73±3 olivine with high-Mg orthopyroxene, Cr-rich Ti-Fe oxides and minor plagioclase and high-Ca pyroxene. Microtextural and petrological analysis reveals that these minerals crystallized at equilibrium. In addition, these boulders are different from all the bedrocks analyzed by Perseverance along its traverse which are crustal igneous rocks and sediments. Comparing our data to Martian meteorites and available Mars bulk silicate models (BSM), we discuss that these boulders could represent primitive melts and/or lower crustal material, and we specifically hypothesize that they could be mantle peridotites. We propose that these putative mantle rocks could have been excavated by the succession of impacts from the shallow mantle or lower crust in the Isidis region where Jezero crater is located. These olivine-rich boulders could thereby constitute the first direct analysis of a Martian mantle rock
Automated in situ thermomechanical analysis of cobalt under EBSD
No full textInternational audienceThe present study aims to investigate the mechanical behaviour of pure cobalt in plasticity at varying temperatures, through in situ thermomechanical loadings under Electron Backscattered Diffraction (EBSD) in order to gain a deeper understanding of the various mechanisms that occur. EBSD analysis allows for the determination of microstructural parameters at a refined scale including grain size, grain misorientation, crystallographic and morphologic texture, and phase ratios, which can be employed to establish a correlation between microstructural changes and deformation mechanisms with temperature. Analyses were conducted in situ using either a furnace that can reach 1000 °C, or a 10 kN thermomechanical device, which enables simultaneous heating and mechanical loading. Both test types were automated in the Scanning Electron Microscope (SEM) by correlating the stage movement with the region of interest, enabling EBSD mappings to be acquired always at the same location. Mappings were post-processed via the spherical indexing process, which yields high-quality indexation (with a reduced number of points exhibiting a Confidence Index of less than 0.1), even at high strain levels. Such experiments conducted on cobalt demonstrated austenitic and martensitic transformations between hexagonal close packed and face centred cubic phases with temperature. Indeed, approximately 31.6 % of the initial face centred cubic phase has transformed into the hexagonal phase for 8 % strain during an in situ tensile test. This transformation is initiated in plasticity by dislocation motions in basal planes and subsequently accelerated by the concurrent activation of mechanical twinning. Additionally, an in situ thermal treatment in the SEM enabled the accurate determination of the phase transformation temperature: 460 °C during heating and 350 °C during cooling, corresponding to the points where the cubic phase fraction reaches a 50 % relative change
An approximate dynamic programming approach for multi-stage stochastic lot-sizing under a Decision-Hazard-Decision information structure
No full textInternational audienceThis work studies a combinatorial optimization problem encountered in industrial production planning: the single-item multi-resource lot-sizing problem with inventory bounds and lost sales. The demand to be satisfied by the production plan is subject to uncertainty and only probabilistically known. We consider a multi-stage decision process with a Decision-Hazard-Decision information structure in which decisions are made at each stage both before and after the uncertainty is revealed. Such a setting has not yet been studied for stochastic lot-sizing problems, and the resulting problem is modeled as a multi-stage stochastic integer program. We propose a solution approach based on an approximate stochastic dynamic programming algorithm. It relies on a decomposition of the problem into single-stage sub-problems and on the estimation at each stage of the expected future costs. Due to the Decision-Hazard-Decision information structure, each nested single-stage sub-problem is itself a two-stage stochastic integer program. We therefore introduce a Benders decomposition scheme to reduce the computational effort required to solve each nested sub-problem, and present a specialpurpose polynomial-time algorithm to efficiently solve the single-scenario second-stage sub-problems involved in the Benders decomposition. The results of extensive simulation experiments carried out on large-size randomly generated instances are reported. They demonstrate the practical benefit, in terms of the actual production cost, of using the proposed approach as compared to a naive deterministic optimization approach based on the expected demand
Identification of rare missense variants reducing cathepsin O secretion in families with intracranial aneurysm
No full textInternational audienceAimsIntracranial aneurysm (IA) is a common cerebrovascular abnormality characterized by localized dilation and wall thinning in cerebral arteries, which can rupture and lead to fatal subarachnoid haemorrhage. Although genetic factors can contribute to IA, the genetic pre-disposition of IA is largely unknown. This study aims to identify rare functional variants associated with IA in families with multiple affected subjects and explore their impact on IA pathophysiology.Methods and resultsBy combining whole-exome sequencing and identity-by-descent analyses, we have identified two rare missense variants in the CTSO gene associated to IA in two large families with multiple affected subjects. We found that the cysteine-type papain-like cathepsin O (CTSO) encoded by CTSO is expressed in the circle of Willis of mice and in the wall of human IA domes. Stretching of vascular smooth muscle cells (VSMC) induced CTSO secretion. CTSO controls VSMC migration and adhesion to the extracellular matrix, and directly interacts with fibronectin (FN). CTSO depletion, or expression of the two CTSO variants, which are poorly secreted, increased the amount of FN. Moreover, CTSO depletion augmented VSMC stiffness, which was reduced by the addition of exogenous CTSO.ConclusionCollectively, our findings identify CTSO as a potential new player in arterial remodelling, regulating FN deposition and VSMC function, supporting the causal role of rare coding CTSO variants in familial forms of IA
Optimal Formalin-Fixed Paraffin Embedded Sample Preservation for Efficient Staining in Multiplex Imaging
No full textInternational audienceThe accuracy of immunohistochemical techniques depends critically on the preservation of antigenic integrity in tissue samples. Although formalin-fixed paraffin-embedded tissues are commonly used for long-term storage, several studies reported signal degradation over time. However, the extent of this degradation and the influence of storage conditions on a wide range of markers remain poorly characterized. In this study, tissue blocks collected over an eight-year period and tissue sections stored under different conditions (room temperature, 4°C, -20°C, -80°C) were analyzed. Twenty-five antibodies targeting immune, stromal, and structural markers were used to stain four different tissue sections. Samples were acquired using imaging mass cytometry (IMC). Signal intensities were first quantified, then the data were analyzed, before and after normalization using imcRtools pipeline. A gradual loss of signal intensity was observed in blocks stored at room temperature for more than six years, affecting the detection of certain markers regardless of tissue type. For some sections, significant signal degradation was observed after only one week at room temperature and for others after one month of storage. Markers such as CD20, CD45, and CD45RA proved to be particularly sensitive. Storage at -20°C or -80°C preserved the quality of the staining, whereas storage at 4°C only allowed partial preservation. Normalization corrected some variations but did not enable the recovery of signals that were severely altered or absent. Commonly used room temperature storage causes gradual reduction in IMC-detected immunoreactivity, which may affect scientific interpretation and diagnosis. Storing sections at -20°C is, therefore, an effective and accessible solution. For retrospective studies, we recommend using blocks that are less than six years old. Overall, these results highlight the importance of pre-established standardized preservation protocols to ensure the reproducibility of analyses
AMH as a marker for resumption of ovarian function after chemotherapy: an IPD meta-analysis and systematic review
No full textInternational audienceBackground: In premenopausal women with breast cancer, chemotherapy often leads to amenorrhea that could be temporary or permanent. Anti-Müllerian hormone (AMH) is a potential biomarker predicting resumption of ovarian function, an outcome that aids in the decision making for endocrine therapy. This study aimed to determine the predictive value of pre-chemotherapy AMH levels for resumption of ovarian function.Methods: We conducted a systematic review and individual patient data (IPD) meta-analysis. Online databases were searched using terms including: AMH, prediction, menses, menses recovery, amenorrhea, chemotherapy-related amenorrhea, anovulation, menopause, infertility, ovarian reserve, premenopausal, breast cancer, chemotherapy. The study protocol was registered with PROSPERO (CRD42021233966).Results: The systematic review included 31 studies, with 26 contributing to the meta-analysis. Eleven studies provided IPD from 1,029 women. Ovarian function resumption rates varied from 24 % to 61 % depending on follow-up time. Pre-chemotherapy AMH was significantly higher in women whose ovarian function resumed, standardized mean difference 0.94 (95 % CI 0.65-1.22) and showed good predictive ability for resumption of ovarian function (AUC 0.79-0.83). However, the identified cut-off values for pre-chemotherapy AMH gave high false negative rates and differed a lot between studies which was much determined by follow-up time, age and used AMH assay.Conclusion: Pre-chemotherapy AMH shows association with ovarian function resumption, but a clinically reliable cut-off across assays could not be established using individual patient data. Therefore, due to high inter-assay variability, AMH is not suitable for optimizing endocrine therapy in premenopausal breast cancer patients at this time. Standardizing AMH assays can help in further research into a cut-off value
ὀλίγ’ ἀληθῆ, πολλὰ δὲ ψευδῆ (Eur., IA, 957): Calchas, des prophéties homériques aux fake news euripidéennes
No full textInternational audienceτίς δὲ μάντις ἔστ᾽ ἀνήρ, | ὃς ὀλίγ᾽ ἀληθῆ, πολλὰ δὲ ψευδῆ λέγει | τυχών (« Mais quel genre d’homme est le devin ? C’est celui qui se trouve, au hasard, dire peu de vérités et beaucoup de mensonges. » IA, v. 956-958). Cette charge euripidéenne vise Calchas, un personnage auréolé d’un prestige en partie construit dans l’Iliade (I, 68-120 et II, 299-332). Or, de l’épopée à la tragédie, la voix narrative omnisciente de l’aède cède la place à une polyphonie qui laisse entendre, en particulier chez Euripide (IA, IT, Hel.), des propos contradictoires sur un devin aussi discret qu’efficient, rouage déterminant des intrigues confiné dans l’espace extra-scénique. Devin politicien, il intervient en tragédie pour prescrire le sacrifice d’Iphigénie, lequel fait l’objet d’une vive désapprobation qui confronte l’autorité de Calchas à des critères aussi bien épistémiques (sur la véracité des prophéties) qu’éthiques (sur la justice voire l’humanité de ses prescriptions). Or, au théâtre, il n’est pas certain que les paroles des personnages ou l’agencement dramaturgique des événements permettent toujours d’arbitrer en faveur de Calchas, bien au contraire. Nous nous proposons ici de mobiliser les outils d’analyse de la narratologie appliquée aux textes antiques2 pour évaluer la façon dont l’insertion de ses prédictions dans les discours rapportés des autres personnages laisse davantage entendre les soupçons envers ses prophéties, toujours en attente de preuve. En considérant ses prises de parole au prisme du concept de fake news3, nous envisagerons ce personnage comme un catalyseur des tensions entre un savoir divin et sa transmission, voire sa manipulation, dans la sphère politique. Plus encore que la parodos de l’Agamemnon, le récit final du messager de l’Iphigénie à Aulis pose la question suivante : a-t-on vraiment de bonnes raisons de croire les dires de Calchas
A possible secular drift of atomic clocks
No full textArguments in favor of the hypothesis that the tick rate of atomic clocks is drifting are examined. The main one is the existence of a preferred value for the relative drift of the period of millisecond pulsars, which is otherwise left unexplained. Other arguments, like the drift of the frequency of sapphire oscillators, the Earth-Moon distance and the Pioneer anomalies are less convincing since other factors are known to play a key role. Interestingly, the corresponding drift of atomic spectra could contribute significantly to the value of the Hubble constant, thus eliminating the age problem of ΛCDM, which has recently been exacerbated by the discovery of mature galaxies at redshifts as high as 14. Such a drift is likely due to an increase of the gravitational field felt by the atomic clocks.</div
Large-scale meta-analysis and precision functional assays identify FANCM regions in which PTVs confer different risks for ER-negative and triple-negative breast cancer
No full textInternational audienceThe breast cancer risk conferred by germline protein truncating variants (PTVs) in known and putative breast cancer genes has been extensively investigated. However, the effect of FANCM PTVs on breast cancer risk remains unclear. Our previous clinical, genetic and functional results on the N-terminal p.Arg658∗ and the two C-terminal p.Gln1701∗ and p.Gly1906Alafs∗12 variants suggested that FANCM PTVs may confer different risks for ER-negative (ER-neg) and triple-negative (TN) breast cancer subtypes. Here, we performed meta-analyses of seven studies totaling 144 681 breast cancer cases and 123 632 controls. FANCM PTVs were tested for association with breast cancer risk overall and the disease clinical subtypes by single variant and burden analyses. Two CRISPR-Cas9-based functional assays were also conducted to test the fitness of cells after knock-in of the p.Arg658∗, p.Gln1701∗ and p.Gly1906Alafs∗12 PTVs and the sensitivity of different FANCM regions to genome editing. Our results suggest that the N-terminal FANCM region upstream of p.Tyr725 harbors essential functions, whereas downstream regions appear dispensable. This is supported by our genetic data which indicate that all FANCM PTVs, excluding the two C-terminal p.Gln1701∗ and p.Gly1906Alafs∗12, are associated with an increased risk of ER-neg (OR = 1.41, P = 0.023) and TN (OR = 1.64, P = 0.0023). Notably, PTVs upstream of AA position 670 are associated with a moderate risk of developing TN breast cancer, and that even when the p.Arg658∗ carriers were excluded from the analysis. Importantly, our results confirm previous data indicating that p.Arg658∗ carriers are at moderate risk of developing ER-neg (OR = 2.08, P = 0.030) and TN (OR = 3.26; P = 0.0034), whereas carriers of p.Gln1701∗ and p.Gly1906Alafs∗12 should not be considered at increased risk. Our data are useful for counseling carriers of FANCM PTVs, but further analyses are warranted to obtain more precise risk estimates