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On the first hitting time of a high-dimensional orthant
No full textInternational audienceWe consider a collection of independent standard Brownian particles (or random walks), starting from a configuration where at least one particle is negative, and study the first time they all become positive. This is clearly equivalent to studying the first hitting time of the positive orthant or the first exit time from the complement of the positive orthant. While it turns out to be possible to compute the distribution of these hitting times for one and two particles, the distribution (and even its tail asymptotics) is not known in closed form for three or more particles. In this paper we study the tail asymptotics of the distribution as the number of particles tends to infinity. Our main techniques come from spectral geometry: we prove new asymptotic estimates for the principal eigenvalue of the complement of a high-dimensional orthant, which we believe are of independent interest
Archives et arts de l’éphémère à Rome (1644-1750)
No full textInternational audienceL’intervention part du constat que l’histoire des arts à Rome sous l’Ancien Régime est dominée par les études sur l’architecture, les monuments, la peinture et la sculpture, c’est-à-dire les arts dont les réalisations tangibles ont survécu aux invasions, aux vols, aux restaurations, aux réemplois, à la rénovation urbaine et à la pollution moderne. Les arts plus éphémères, comme le théâtre, la musique et la danse, ont laissé des traces dans des partitions et des tablatures notées, des livrets, des traités chorégraphiques, des costumes miraculeusement conservés, des instruments de musique, des représentations de scènes théâtrales, des correspondances, etc. À partir de l’expérience d’un programme de recherche collectif (PerformArt) qui a rassemblé une trentaine de personnes de 2016 à 2022 et qui visait à enrichir notre compréhension de l'histoire des arts du spectacle au sein de la noblesse romaine au XVIIe et au XVIIIe siècle en exploitant la documentation contenue dans les archives de onze familles aristocratiques, il s’est agi de proposer quelques réflexions sur la méthode à adopter pour étudier ces vestiges de pratiques extraordinairement développées, et sur les résultats que l’on peut espérer obtenir. On verra comment les spectacles exposaient la magnificence de leurs commanditaires, au même titre que la décoration de leurs carrosses ou que les riches reliures des ouvrages de leurs bibliothèques. Cette analyse, en montrant quelle rentabilité politique ou symbolique les grandes familles romaines attendaient de leurs investissements dans les arts du spectacle, ouvre des pistes de réflexion passionnantes pour le mécénat dans nos sociétés modernes
La musica nel suo contesto sociale: Dalla ricerca personale all’indagine collettiva
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Jâlons (51), L'Ajau, Phase 1. des occupations allant du Néolithique à l'Époque moderne en vallée de la Marne.
No full text2 VOLUMESLa fouille menée sur le site de Jâlons, L'Ajau, phase 1 s'est tenue en deux temps : du 30 août au 8 septembre 2021 puis du 7 juin au 10 août 2022. Elle fait suite à un arrêté de prescription émis par le service régional d'Archéologie de la région Grand-Est, succédant à un diagnostic mené par l'Institut national de recherches archéologiques préventives en 2017 (Gazenbeek 2018). L'opération intervient en amont d'un projet d'extension de carrière de granulats sur cette commune par la Société des Carrières de l'Est - Établissement Morgagni. L'opération se situe dans le département de la Marne (51), à mi-chemin entre Châlons-en-Champagne et Épernay, au lieu-dit L'Ajau. L'emprise concernée correspond au sud des parcelles ZD 3, 4 et 30, et s'étend sur 24 251 m². Les premières occupations du site sont matérialisées par la découverte, dans l'angle nord-est de l'emprise, de dix fosses profondes de type Schlitzgruben qui ont pu être datées du Néolithique ancien. Une vaste zone d'habitat vient ensuite s'implanter dans la plaine alluviale, de part et d'autre d'un paléochenal, durant la transition entre le premier et le second âge du Fer (transition Hallstatt - La Tène A). Elle se compose d'une vingtaine de constructions sur poteaux, de fosses d'extraction, de stockage et de rejet ainsi que de puisards. Durant le second âge du Fer, de nombreux épisodes de crue de la Marne ont inondé le site, déposant successivement des alluvions et transportant ainsi de nombreux éléments archéologiques issus de sites alentours. Ces éléments sont représentés majoritairement par de la céramique, de la faune et du mobilier lithique. Ce mobilier rassemble une vaste chronologie allant du Néolithique à l'âge du Fer. Enfin, des fossés parcellaires se sont implantés dans l'angle nord-est de l'emprise de fouille probablement durant l'Antiquité. Cet ensemble de fossés a pu perdurer jusqu'à l'Époque moderne où ils sont encore visibles sur le cadastre napoléonien de 1809
La malattia dei moderni. Presenze e funzioni del mal francese nella letteratura italiana (1494-1650)
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Characterization of Salmonella adaptation in response to phage treatment in broiler chickens
No full textInternational audienceSalmonella constitutes a significant public health threat due to its widespread association with foodborne diseases, particularly those associated with contaminated poultry products. In this context, phage therapy has emerged as a promising strategy to control these infections. However, the natural emergence of phage-insensitive bacterial strains poses challenges for the efficacy of phage therapy. Understanding the adaptive response of Salmonella to phages in vivo is essential for developing effective therapeutic interventions. This study investigates the adaptive responses of Salmonella to phages-induced challenges, deciphers the underlying mechanisms and analyzes their in vivo consequences. Following repeated administrations of a six-phage cocktail in chickens, a panel of 145 random Salmonella isolates was recovered and characterized. Among these, 48% exhibited reduced sensitivity to a single phage from the phage cocktail, without evidence of cross-resistance; the vast majority of isolates remained susceptible to other phages. We identified two distinct bacterial adaptation profiles both associated with modifications in the lipopolysaccharide (LPS) structure, which appears as the phage receptor. The first profile displayed a complete resistance phenotype resulting in a rough-type Salmonella due to a genetic mutation in the rfbD gene involved in LPS biosynthesis. The second profile exhibited a transient and partial resistance phenotype, due to increased LPS glucosylation, likely associated to phase variation. This phenomenon leads to coexistence of phages and bacteria within the host. Furthermore, we highlighted that these modifications could in part impair Salmonella’s ability to colonize the gut. Overall, our findings suggest that phage-induced evolutionary pressure may be harnessed not only to control bacterial populations but also to attenuate their pathogenicity. Therefore, bacterial resistance what is often view as a limitation of phage therapy may be leveraged as a functional advantage in phage cocktail design
Transmedial recontextualization of new scientific research claims
No full textInternational audienceThis study adopts the “continuity” model of the dissemination of expert knowledge to wider audiences and proposes a nuanced account of how the same new knowledge claim is transmedially repurposed across different genres for different digital audiences. Five series of documents on environmental topics were collected from the Nature platform, with each series comprising the same set of four genres, totalling 20 documents (47,250 words): the original research article (RA); the Nature News & views article, incorporating expert opinion on the initial RA; the Nature podcast, i.e. an interview with the RA author(s); and a popular science magazine article reporting on the RA. We examine how the scientific content, both verbal and visual, is tailored to facilitate comprehensibility for less specialized audiences by analyzing the rhetorical structure of the three recontextualized genres, the strategies used to handle specialized terminology, and the types of visual material contained. The recontextualized genres also set up different relationships with their respective audiences to those in the RAs by using various engagement strategies to interest and involve them. The engagement and interactional features focused on in this study include a contrastive analysis of reader/audience mentions and passives, the use of questions, and the adaptation of titles. By keeping the scientific topic constant across the dataset, we show the fine gradations in how the same knowledge claim is adapted, assessed and circulated among different audiences
Methylation analysis as a diagnostic tool for sweat gland tumours classification with emphasis on the distinction between digital papillary adenocarcinoma and mimickers
No full textInternational audienceAims: Digital papillary adenocarcinoma (DPA) is a rare sweat gland carcinoma arising on acral sites. The main differential diagnosis included tubular adenoma, hidradenoma, poroid hidradenoma, and mixed tumours, distinction between DPA and these mimickers being crucial for therapeutic management. Recently, HPV42 was identified as the main oncogenic driver of most DPA. Controversially, a few sweat gland tumour cases diagnosed as “DPA” but lacking the HPV42 genome and harbouring instead a BRAF V600E mutation, a genetic hallmark of tubular adenomas, have been recently described. Methylation analysis is a powerful tool for tumour classification systems. In this context, the aim of the present study is to evaluate the accuracy of methylation analysis for sweat gland tumour classification with special emphasis on the distinction between DPA and mimickers. Methods and results: Twelve DPA, 11 tubular adenomas, 12 hidradenomas, 8 apocrine and 6 eccrine mixed tumours, 7 poromas and 6 adnexal sweat gland carcinoma not otherwise specified (NOS) were submitted for DNA methylation profiling. The results of this analysis show that most of these tumour types formed their own unique cluster, setting them apart from the others. In particular, DPA cases clustered together and were distinct from other tumour entities including tubular adenomas. Conclusions: Our data support the distinction between DPA and tubular adenomas as two unique entities and further confirm DNA methylation profiling as a relevant tool for tumour classification
Faute de la victime ou obligation de minimiser le dommage : quel fondement pour réduire le droit à réparation ?
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Clinical, Morphologic, and Genomic Findings in Spitz Tumors With RET Fusion: A Series of 31 Cases
No full textInternational audienceRET-fused Spitz neoplasms represent a rare and poorly characterized category of Spitz tumors. Here we describe the clinical, histologic, and molecular findings of 31 Spitz neoplasms with RET fusion diagnosed as Spitz nevus (n = 16), atypical Spitz tumors (n = 13), and Spitz melanoma (n = 2). The lesions mainly occurred in children and young adults of both sexes with a predilection for the extremities. Microscopically, they were mainly symmetrical compound melanocytic neoplasms with a dome-shaped/slightly raised silhouette predominantly composed of epithelioid, spindled, and/or smaller nevoid melanocytes arranged in confluent nests. Dyscohesive melanocytes within the nests in the upper part of the lesions, prominent Kamino bodies, giant multinucleated melanocytes, variable pigmentation, and increased vascularity with vascular ectasia were frequent features. RNA sequencing detected 9 different 5' (N-terminus) fusion partners, including KIF5B (n = 8), LMNA (n = 7), CCDC6 (n = 6), OPTN (n = 3), MYO5A (n = 2), and NCOA4, ERC1, MYH9, AGAP3 (n = 1). Of these, OPTN::RET and AGAP3::RET represent novel fusions, and 3 further 5' fusion partners, namely NCOA4, ERC1, and MYH9, have never been reported in Spitz tumors. Although as a whole group, the tumors showed a heterogeneous histopathologic presentation, correlation of the morphologic features and the 5' fusion partners demonstrated certain associations. Nevoid melanocytes were exclusively encountered in cases with KIF5B fusion partner. Neuroid-like appearances with intersecting fascicles of spindled cells typified both MYO5A-fused cases. Epithelioid melanocyte population dominated cases with LMNA and CCDC6 fusion partners. Transepidermal elimination/floating intraepidermal nests of pigmented spindled and epithelioid melanocytes were observed in the OPTN subgroup. The remaining cases with less frequent 5' fusion partners manifested in general more atypical histopathologic features, including nuclear pleomorphism, high mitotic count, atypical mitoses, and sheet-like growth pattern. Melanoma fluorescence in situ hybridization probe kit targeting RREB1, MYC, CDKN2A, and CCND1, was negative for copy number variation in 4 cases tested, including 2 cases with complete p16 nuclear loss on immunohistochemistry. Array comparative genomic hybridization was performed in 3 lesions and detected numerous segmental chromosomal imbalances in 2 of them that were diagnosed as Spitz melanoma. DNA and RNA sequencing detected several further genomic alterations, including POU2F3 overexpression in 3 highly pigmented lesions. Further studies are needed to confirm possible correlations between the microscopic features and a particular fusion partner (or additional genetic events) in RET-fused Spitz neoplasms