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Multi-Score Reinforcement Learning for High-Tg Polyimide Design
No full textInternational audienceThis study explores strategies to guide the generation of polyimides with high glass transition temperatures (Tg > 750 K) through reinforcement learning. We present a systematic computational framework for analyzing and combining multiple scoring functions into a single score in reinforcement learning (RL) for molecular design. Rather than relying solely on a single scoring function based on a predictive model, we examine a range of complementary scores, including a novel naı̈ve high-Tg score and various Tanimoto similarity-based scores. We analyze these scores both individually and in combination with the predictive model-based score in order to assess their influence on the structural diversity and quality of the generated polymers. In addition, we investigate several methods for combining scores, such as arithmetic, geometric, and harmonic means, as well as a novel exponential–logarithmic function, referred to as ExpAgg. We evaluate how these aggregation strategies affect the outcomes of molecular generation across different reinforcement learning configurations. Our findings show that the choice of score combination method significantly impacts both the quality and diversity of generated polymers. The proposed ExpAgg achieves superior performance in multiple settings, revealing nontrivial interactions between score compatibility and model convergence. While the predictive model exhibits underestimation in the out-of-distribution region (>800 K), our multiscore framework successfully generates chemically reasonable high-Tg candidates. Based on these insights, we provide practical guidelines for selecting aggregation functions when fusing two scores. This case study on high-Tg polyimide generation demonstrates how score aggregation strategies influence molecular RL outcomes; broader generalizability to other molecular design tasks remains to be investigated. This work emphasizes the importance of moving beyond simple weighted averages in order to enhance targeted molecular design
Gli startupper francesi se ne fregano: un’analisi multimodale della locuzione «on s’en fout»
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Efficacy, safety, pharmacokinetics, immunogenicity, and serum neutralizing activity of AZD7442 (tixagevimab-cilgavimab) in patients hospitalized with COVID-19: long-term results from the DisCoVeRy trial
No full textInternational audienceObjectives: To report long-term clinical efficacy, safety, pharmacokinetics, immunogenicity and seroneutralization results of AZD7442 (monoclonal antibodies tixagevimab-cilgavimab) in patients hospitalized with COVID-19.Methods: In this phase 3, double-blind, randomized, multicentre trial, hospitalized adults with PCR-confirmed SARS-CoV-2 infection were randomly assigned 1:1 to receive AZD7442 or placebo, and followed-up until day 456, with repeated blood sample collections until day 365. Clinical endpoints included clinical status, mortality, rehospitalization, SARS-CoV-2 reinfection, and adverse events. Antidrug antibodies and serum drug concentrations were measured. Analyses were performed on the modified intention-to-treat (mITT) populations, defined as participants who actually received the intervention.Results: Between April 28, 2021, and June 23, 2022, 237 participants were randomly assigned to AZD7442 (n = 127) or placebo (n = 110), and 123 participants actually received AZD7442. Participants were infected with pre-Omicron variants in 58.8% (133/226) of cases, versus 33.2% (75/226) of Omicron BA1, BA2, or BA5, and 8% (18/226) missing data. There was no significant difference in the distribution of the 7-point ordinal scale between the AZD7442 and placebo groups, either on day 15 (primary endpoint) (OR = 0.93 [0.54-1.61], p 0.81), or any other time point. Significantly more rehospitalizations occurred between discharge and day 456 among participants who received AZD7442 in the global mITT population (OR = 2.04 [1.03-4.05], p 0.04), but not in the antigen-positive mITT population (OR = 1.78 [0.80-3.94], p 0.15). No significant differences were observed in mortality, SARS-CoV-2 reinfection, or adverse events. In the AZD7442 group, 12 of 87 participants (13.8%) had treatment-emergent antidrug antibodies versus 5 of 69 (7.2%) in the placebo group (OR = 2.02 [0.66-6.14], p 0.21). Serum drug concentrations were detectable up to day 365 for all sampled participants (35/35). Neutralizing antibody titres were significantly higher in the AZD7442 group up to day 180.Conclusions: AZD7442 did not demonstrate any clinical benefit and was safe up to 15 months. This study also provides valuable data on the pharmacokinetics, immunogenicity, and neutralizing activity of AZD7442 in patients hospitalized with COVID-19
Raclet: the ramp above critical level endurance test to evaluate critical force in isometric task
No full textInternational audiencePurpose. The Ramp Above Critical Level Endurance Test (RACLET) is a novel submaximal test designed to evaluate the parameters of the critical force model without strenuous exercise. This study aimed to validate the RACLET in healthy and pathological populations and to assess its reliability, concurrent validity, and predictive capacity.Methods. Sixteen healthy volunteers and ten patients with respiratory pathologies participated in this study. The RACLET consisted of a decreasing ramp force starting at 60% and ending at 15% of the maximum force for a total duration of 425 s with brief regular maximal voluntary contractions.Results. The goodness of fit for the RACLET model on the maximal contraction force was excellent in both populations (median r2 = 0.95). In patients, RACLET parameters demonstrated excellent reliability (ICC > 0.90). The concurrent validity of the critical force estimate compared with the all-out method was high (error: 0.3±7.4%). The model’s predictive capacity for time-to-exhaustion and fatigue during constant-intensity exercise was excellent (r2 = 0.910 and 0.907, respectively).Conclusion. The RACLET is thus confirmed as a reliable, valid, and feasible method for determining critical force parameters without strenuous exertion. Its strong predictive accuracy for both time-to-exhaustion and fatigue establishes it as a robust submaximal alternative to all-out protocols for use in both healthy and vulnerable populations
Primates dans la recherche biomédicale : éthique, enjeux et avancées
No full textInternational audienceBiomedical research relies on a variety of animal models, each providing specific insights into physiology, immunity, behaviour, development or vulnerability to disease. In France, as throughout Europe, this research is conducted under some of the world's most stringent regulatory and ethical standards, as defined by European Directive 2010/63/EU on animal research. In 2023, non-human primates (NHP) represented 0.2% of animal use in biomedical research protocols, according to the statistical survey 'Use of animals for scientific purposes in French establishments' published by the French Ministry of Higher Education and Research. This use is governed by the internationally recognised 3R principle (Replace, Reduce, Refine), which forms the foundation of all modern animal research. In France, these principles are promoted and reinforced by the French Center for the 3R (FC3R), whose mission is to support the scientific community in adopting more responsible, transparent and innovative practices
Some aspects of topological dynamics of Polish groups: With an introduction to descriptive set theory
No full textInternational audienceThe first half of these notes presents some aspects of the theory of continuous actions of Polish groups on compact spaces, leading to the Kechris--Pestov--Todorcevic correspondence. The second part provides an introduction to descriptive set theory and culminates in a proof, due to B. Miller, of the G_0 dichotomy theorem due to Kechris, Solecki and Todorcevic
Decoding Ink in Historical Documents: Anomaly Localization and Source Separation
No full textInternational audienceIn this paper, we attempt to make ink talk in historical documents by extracting visual information materialized by the trace left on the support, thus addressing two tasks: anomaly localization in hand-pressed ornaments in the framework of Rey's publishing and source separation in Queen Marie-Antoinette's correspondence where the letters are hidden with loops. Anomalies are defined as changes in shape with respect to the original skeleton. A logarithmic image processing is applied for both anomaly visualization and image generation by mixing letters with loops to train a source separation model, respectively. Such an image generation is tackled from spectral modeling in halftoning
Post-progressisme et néo-urbaphobie. Le crépuscule de la ville radieuse ?
No full textInternational audienceL’urbaphilie a longtemps constitué l’expression d’un idéal progressiste d’inspiration post-marxiste, tandis que l’urbaphobie était généralement associée à une pensée réactionnaire. Toutefois, ces dernières années — sous l’effet de dynamiques telles que l’écologie radicale, le mouvement des Gilets jaunes ou encore la crise sanitaire — cette opposition a été remise en question : les métropoles se trouvent désormais contestées, voire fuies. Dans ce contexte émerge une forme de néo-urbaphobie, dont le présent chapitre se propose d’examiner les différentes formulations observées dans la presse écrite
North–south Holocene seasonal contrast on the Italian peninsula: Clarification of the latitudinal transition zone based on the multi-proxy study of Lago Grande di Monticchio
No full textInternational audienceItaly’s Holocene climate can be characterised by a latitudinal division with a climatic contrast between the northern and southern regions, notably characterised by a stronger winter–summer precipitation seasonality in southern regions. The latitudinal boundary is located between latitudes 40°and 43°N, creating a climatic transition zone. However, the mechanisms underpinning this hydro-climatic partition remain poorly understood, due in part to a scarcity of precisely dated, high-resolution records at key latitudes. Lago Grande di Monticchio ( 41°N) lies within this critical transitional band and presents a valuable opportunity to refine the latitudinal boundary location. Lago Grande di Monticchio is one of southern Italy’s most comprehensively studied sediment archives, stretching back to the last interglacial. In this study, we employ a novel, high-resolution sediment core from Monticchio, applying a multi-proxy methodology that combines branched glycerol dialkyl glycerol tetraether (brGDGT) and pollen data to reconstruct seasonal temperature and precipitation changes during the Holocene. Results confirm that temperature reconstructions derived from brGDGT and pollen records are particularly consistent for most of the signal. Comparison with other palaeoclimate records and proxies in Italy allowed us to place Lago Grande di Monticchio’s climate signal within southern climate regimes (i.e., summer cooling and aridity in contrast to wetter and warmer winters), corresponding to a stronger ”Mediterraneanization” process throughout the Holocene. Multi-proxy comparison indicates that the most marked contrast during summer likely lies near the upper bound of 41°–43°N. Persistent inconsistencies in the transition zone suggest added climatic complexity around 43°N, involving ocean-atmospheric teleconnections and local topography. We advocate further high-resolution, multi-proxy palaeoenvironmental studies in this transitional latitude band to refine understanding of the north–south hydro-climatic boundary across Italy in the Holocene
The Night Shift of Heat: How Real-World Exposure and Human Diversity Redefine Vulnerability
No full textunder reviewHeat-health science remains dominated by daytime, outdoor metrics, yet recovery is lost at night and in indoor environments where heat actually accumulates. I argue that heat should be reframed as a 24-hour ecological exposure centred on nocturnal recovery and human diversity. Integrating sleep, mental health, metabolism and sex-specific physiology into multimodal real-world monitoring offers a path to redefine exposure metrics and design fairer, more effective adaptation strategies for a rapidly warming world. Night-time Heat: The Critical Yet Missing ExposureHeat is one of the fastest-growing environmental health threats, with global exposure and inequalities sharply rising 1 . Yet most assessments still prioritize daytime outdoor indices, overlooking the phase of the 24-hour cycle when vulnerability intensifies 2 . In much of the world, nights are warming faster than days 1, 3 , while humidity and urban thermal inertia increasingly constrain heat dissipation 4-6 . Temperature-humidity interactions differ physiologically across daytime wakefulness and nighttime sleep, involving distinct thermoregulatory processes 4 . Nighttime therefore constitutes the primary window for psychophysiological recovery, as sleep supports the restoration of key physiological, neural and emotional functions 3, 6, 7 , all of which depend on adequate nocturnal heat loss, which warm nights increasingly fail to provide 3, 5 . Even modest night-time warming shortens and</div