TEL is a sequence-specific transcriptional repressor.

TEL is a gene frequently involved in specific chromosomal translocations in human leukemia and sarcoma that encodes a member of the ETS family of transcriptional regulators. TEL is unusual among other ETS proteins by its ability to self-associate in vivo, a property that is essential to the oncogenic activation of TEL-derived fusion proteins. We show here that TEL is a sequence-specific transcriptional repressor of ETS-binding site-driven transcription of model and natural promoters

L'impact spatial et énergétique des data centers sur les territoires

Face à la croissance massive des échanges de données et des besoins de stockage, l’impact spatial et énergétique des data centers va être de plus en plus structurant pour les territoires. Leur diversité d’usages, d’acteurs, de tailles et d’implantations rend aujourd’hui complexe la lecture de leurs dynamiques et de leurs effets spatiaux.Le présent rapport s’attache donc à donner une image du paysage des data centers en Ile-de-France et dans trois territoires des États-Unis, représentant chacun des situations spatiales et énergétiques différentes (ville dense, espace périphérique, rural). Facteur potentiel de déséquilibre des systèmes énergétiques locaux, objets dont l’accumulation urbaine et la dispersion rurale questionnent, les data centers font ici l’objet d’une analyse approfondie pour mieux appréhender les nouveaux territoires numériques en construction, les solidarités énergétiques à construire et les alliances d’acteurs à mettre en place.Un focus est également réalisé sur les infrastructures numériques alternatives et citoyennes, qui se développent aussi bien en Afrique, Amérique du Sud, que dans les territoires mal couverts en Europe ou aux États-Unis. Dédiées à l’accès à Internet et de plus en plus, aux services d’hébergement et de cloud, elles peuvent constituer une réponse distribuée et pair-à-pair, dont l’impact écologique pourrait finalement se révéler plus limité que les infrastructures centralisées de grande échelle car calibrées au plus près des besoins locaux, mais aussi plus résilientes car moins centralisées techniquement et moins concentrées spatialement. Elles constituent ainsi une option à considérer, soutenir mais aussi à mieux évaluer, pour réduire les impacts spatiaux et énergétiques des data centers.Le rapport propose également des visions prospectives qui combinent des tendances de fond et des signaux faibles pour imaginer les mondes numériques de demain, dont trois possibles sont décrits : « Croissance et ultracentralisation numérique » ; « Stabilisation du Système Technique Numérique et diversité infrastructurelle : quête d’une difficile résilience » ; « Ultradécentralisation numérique : la fin des data centers ? ». Enfin, des recommandations sont proposées autour de 3 axes : les acteurs et la gouvernance ; l’urbanisme et l’environnement ; l’énergie. Des pistes d’approfondissement et d’études sont également présentées

From underground laser scans to 3D urban geological and geotechnical models

International audienceThe near sub-surface geology, say down to 20-30-m-depth, of many cities has been massively exploited for extracting building stones and various other industrial or agricultural materials (gypsum, lime, etc…). The long-term instability of these cavities poses a significant collapse hazard conditioned by their geometry (void location, dimensions and shape) and by their surrounding rock mechanics properties. In this presentation, we show how handheld laser scanning surveys efficiently document geometric variables and can interact with 3D geological modelling of the surrounding rocks. The construction of near-surface urban geological models can then be turned into 3D geotechnical models by attributing geotechnical parameters to rock horizons and ultimately become a key subsurface knowledge component of BIM (Building Information Model). Acquiring surface and subsurface geometry is no longer a challenge thanks to handheld laser scanners. Survey loop traverses can be pieced together to link surface and subsurface geometry with accuracies better than 1 m (an accuracy level compatible with urban risk management maps at 1/5.000) (DEWEZ et al., 2017). However, the hundreds of-millions of 3D points describing the cavity surface cannot be integrated as such into geomodeling software. Too many points with not high enough information. We suggest two different scenarios to perform their integration: (i) as independent validation of geomodeling hypotheses, or (ii) as geomodel constraints. In the first integration scenario, point cloud information is passed to the geomodeling software at a minimal level. A decimated triangular meshed model can be used to intersect the geomodel. Triangulation is performed at the point cloud processing software level (e.g. GeoSLAM desktop or Cloud Compare) and intersection is handled at the geomodelling software level with a generic query concept (here GeoModeller software with a generic query API – LOISELET et al.,2016). In this instance, cavity mesh triangular faces are refined based on the geological model queries (relying on the marching triangles algorithm) and provide geotechnical attributes based on the geological formations given by the geomodel. This scenario offers a visual display of geological properties (Fig. 1) for checking that modelled layers and structures match those observed in underground outcrops. In the second scenario, which is more integrated, higher level information is passed to the geomodelling tool. Planar surfaces of marker horizons are segmented from the point cloud either manually using Compass (THIELE et al., 2017) or semi-automatically with FACETS (DEWEZ et al., 2016) and passed as structural data objects to constrain the geomodel (Fig. 2). This data integration is demonstrated on a ca. 1 ha underground building stone quarry of the eastern suburbs of Orléans, Central France. The cavity was scanned at ca. 1pt/1cm with a Zeb-Revo (90 Mpts underground and 35 Mpts above ground). A geomodel of the subsurface area (Calcaire de Beauce, Tertiary) was created with the GeoModeller software as a tabular sub-horizontal multilayer environment. The geomodel infers rock distribution over a domain of ca. 200 x 200 m with geological and geotechnical information (e.g. limit pressure for dimensioning building foundations). Both approaches leverage a generic API query tool informing which domain surrounds a point and whether a geological contact cross-cuts a triangular face

Application de la théorie de l'information pour l'extraction passive radar en guerre électronique marine

Dans l'environnement électromagnétique naval, les impulsions émises par les radars sont recueillies par des récepteurs passifs. Ces impulsions sont regroupées en blocs selon la similitude de certains paramètres. Le but de cette étude est alors de mettre en place un critère de regroupement des blocs d'impulsions pour reconstruire les formes d'ondes émises par les radars. Cela doit permettre d'obtenir une meilleure qualité d'identification d'émetteur. La méthode de regroupement des blocs utilisée est une méthode de fusion basée sur un calcul d'entropie, l'entropie permettant d'estimer le degré de désordre du signal obtenu pour les cas de fusion envisagés

Case report: Life threatening hyponatremia in infants with urinary tract infections: two cases of type III pseudohypoaldosteronism and review of the literature

We describe two female infants at the age of five and six months with urinary tract infections presenting with vomiting and reduced drinking behavior. On laboratory analysis, severe hyponatremia (106 mmol/L and 109 mmol/L) was seen with hyperkalemia and compensated metabolic acidosis. Endocrinological analyses revealed massively increased levels of aldosterone and renin, leading to the diagnosis of type III pseudohypoaldosteronism (PHA). A review of the current literature 2013–2023 revealed 26 type III PHA cases aged up to ten months with reduced drinking behavior, weight loss and/or failure to thrive being the most common clinical presentations. Given the severe presentation of PHA electrolyte measurements in infants with urinary tract infections and/or in infants with congenital anomalies of the kidney and urinary tract (CAKUT) are strongly recommended

Prevalence and Clinical Associations of Antiphospholipid Antibodies in Systemic Sclerosis: New Data From a French Cross-Sectional Study, Systematic Review, and Meta-Analysis

Objectives: Antiphospholipid antibodies (aPL) can be present in the sera of systemic sclerosis (SSc) patients. This study aimed to determine the prevalence of aPL in a cross-sectional study of SSc patients, to assess their clinical associations, to perform a systematic review of published reports and a meta-analysis to estimate the worldwide prevalence of aPL in SSc.Methods: Two-hundred and forty-nine SSc patients were consecutively tested once for lupus anticoagulant (LA), anticardiolipin (aCL), and anti-β2glycoprotein I (anti-β2GpI) antibodies. Clinical associations with aPL positivity were studied using a logistic regression model. A systematic review of the literature was carried out in PubMed and Embase. Meta-analysis was performed using number of aPL positive (at least one of the three antibodies positive) and negative patients. Meta-regression was used to study potential factors explaining the heterogeneity between studies.Results: In our cross-sectional study, aPL positivity was found in 16 patients (prevalence 6.4%; 95%CI [3.8–10.4]). In multivariate analysis, there was a significant association between aPL positivity and venous thrombosis (VT) (OR 6.25 [1.18–33.00]; p = 0.028) and miscarriage (OR 5.43; 95%CI [1.31–22.13]; p = 0.017). Twenty-four studies were included in the meta-analysis, representing a total population of 3036 SSc patients. The overall pooled prevalence of aPL in SSc was 14% (9–20) with a high degree of heterogeneity among studies.Conclusion: This study found a prevalence of aPL positivity in our SSc population of 6.4% (3.8–10.4) and an overall worldwide pooled prevalence of 14% (9–20). In our SSc population, aPL positivity was associated with VT and miscarriage. These data provide additional insights into the role of aPL in the vasculopathy observed in SSc

Ontogenic Changes in Hematopoietic Hierarchy Determine Pediatric Specificity and Disease Phenotype in Fusion Oncogene-Driven Myeloid Leukemia.

Fusion oncogenes are prevalent in several pediatric cancers, yet little is known about the specific associations between age and phenotype. We observed that fusion oncogenes, such as ETO2-GLIS2, are associated with acute megakaryoblastic or other myeloid leukemia subtypes in an age-dependent manner. Analysis of a novel inducible transgenic mouse model showed that ETO2-GLIS2 expression in fetal hematopoietic stem cells induced rapid megakaryoblastic leukemia whereas expression in adult bone marrow hematopoietic stem cells resulted in a shift toward myeloid transformation with a strikingly delayed in vivo leukemogenic potential. Chromatin accessibility and single-cell transcriptome analyses indicate ontogeny-dependent intrinsic and ETO2-GLIS2-induced differences in the activities of key transcription factors, including ERG, SPI1, GATA1, and CEBPA. Importantly, switching off the fusion oncogene restored terminal differentiation of the leukemic blasts. Together, these data show that aggressiveness and phenotypes in pediatric acute myeloid leukemia result from an ontogeny-related differential susceptibility to transformation by fusion oncogenes. SIGNIFICANCE: This work demonstrates that the clinical phenotype of pediatric acute myeloid leukemia is determined by ontogeny-dependent susceptibility for transformation by oncogenic fusion genes. The phenotype is maintained by potentially reversible alteration of key transcription factors, indicating that targeting of the fusions may overcome the differentiation blockage and revert the leukemic state.See related commentary by Cruz Hernandez and Vyas, p. 1653.This article is highlighted in the In This Issue feature, p. 1631

Potential Utility of Plasma P-Tau and Neurofilament Light Chain as Surrogate Biomarkers for Preventive Clinical Trials

OBJECTIVE: To test the utility of longitudinal changes in plasma phosphorylated tau 181 (p-tau181) and neurofilament light chain (NfL) as surrogate markers for clinical trials targeting cognitively unimpaired (CU) populations. METHODS: We estimated the sample size needed to test a 25% drug effect with 80% of power at a 0.05 level on reducing changes in plasma markers in CU participants from Alzheimer's Disease Neuroimaging Initiative database. RESULTS: We included 257 CU individuals (45.5% males; mean age = 73 [6] years; 32% β-amyloid [Aβ] positive). Changes in plasma NfL were associated with age, whereas changes in plasma p-tau181 with progression to amnestic mild cognitive impairment. Clinical trials using p-tau181 and NfL would require 85% and 63% smaller sample sizes, respectively, for a 24-month than a 12-month follow-up. A population enrichment strategy using intermediate levels of Aβ PET (Centiloid 20-40) further reduced the sample size of the 24-month clinical trial using p-tau181 (73%) and NfL (59%) as a surrogate. DISCUSSION: Plasma p-tau181/NfL can potentially be used to monitor large-scale population interventions in CU individuals. The enrollment of CU with intermediate Aβ levels constitutes the alternative with the largest effect size and most cost-effective for trials testing drug effect on changes in plasma p-tau181 and NfL