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CREB3 gain of function variants protect against ALS
No full textInternational audienceAmyotrophic lateral sclerosis (ALS) is a fatal and rapidly evolving neurodegenerative disease arising from the loss of glutamatergic corticospinal neurons (CSN) and cholinergic motoneurons (MN). Here, we performed comparative cross-species transcriptomics of CSN using published snRNA-seq data from the motor cortex of ALS and control postmortem tissues, and performed longitudinal RNA-seq on CSN purified from male Sod1G86R mice. We report that CSN undergo ER stress and altered mRNA translation, and identify the transcription factor CREB3 and its regulatory network as a resilience marker of ALS, not only amongst vulnerable neuronal populations, but across all neuronal populations as well as other cell types. Using genetic and epidemiologic analyses we further identify the rare variant CREB3R119G (rs11538707) as a positive disease modifier in ALS. Through gain of function, CREB3R119G decreases the risk of developing ALS and the motor progression rate of ALS patients
The anatomy of open innovation failure: managerial-level evidence from romanian SMEs
No full textInternational audienceWhile open innovation (OI) can boost innovation performance, many SMEs struggle to implement it due to limited resources and structural constraints. Despite its importance, OI failure remains underexplored, particularly at the managerial level. This study, grounded in Upper Echelons Theory (UET), investigates how SME managers’ personal factors contribute to OI failure, understood as the unsuccessful adoption and execution of OI practices. Based on an ongoing inductive qualitative study involving ten semi-structured interviews with Romanian SME leaders and secondary national data, our findings highlight three key dimensions: (1) antecedents linked to managerial traits, such as limited strategic planning, lack of commitment, and weak external collaboration capacity; (2) the failed execution of inbound and outbound OI practices; and (3) consequences including reduced innovation and competitiveness. This research advances OI and UET literature by highlighting the human side of OI failure and providing a framework to help SMEs address it
Uniform-in-time propagation of chaos for mean field Langevin dynamics
No full textInternational audienceWe study the mean field Langevin dynamics and the associated particle system. By assuming the functional convexity of the energy, we obtain the -convergence of the marginal distributions toward the unique invariant measure for the mean field dynamics. Furthermore, we prove the uniform-in-time propagation of chaos in both the -Wasserstein metric and relative entropy.Nous étudions la dynamique de Langevin à champ moyen et le système de particules correspondant. En supposant la convexité fonctionnelle de l’énergie, nous obtenons la convergence dans des distributions marginales vers l’unique mesure invariante pour la dynamique à champ moyen. De plus, nous montrons la propagation du chaos uniforme en temps à la fois dans la métrique de Wasserstein d’ordre 2 et dans l’entropie relative
Option market making with hedging-induced market impact
No full textInternational audienceThis paper develops a model for option market making in which the hedging activity of the market maker generates price impact on the underlying asset. The option order flow is modeled by Cox processes, with intensities depending on the state of the underlying and on the market maker's quoted prices. The resulting dynamics combine stochastic option demand with both permanent and transient impact on the underlying, leading to a coupled evolution of inventory and price. We first study market manipulation and arbitrage phenomena that may arise from the feedback between option trading and underlying impact. We then establish the well-posedness of the mixed control problem, which involves continuous quoting decisions and impulsive hedging actions. Finally, we implement a numerical method based on policy optimization to approximate optimal strategies and illustrate the interplay between option market liquidity, inventory risk, and underlying impact
L’examen du chef-d’œuvre comme classement dans le métier: Réflexions sur le cas des maçons strasbourgeois du XVIIIe siècle
No full textInternational audienceThe paper describes the procedure for submitting a masterpiece to the Strasbourg masons' guild. Thereafter, it shows how the results of the examination, recorded in protocols (1708-1790) and testifying for various motives, led to modulations in the rights associated with master status. The examination thus appears not only as a ritual legitimising the separation between masters and journeymen, but also as a moment of at least temporary classification in a hierarchy between masters.Après avoir décrit la procédure de soumission d’un chef-d’œuvre dans la corporation des maçons de Strasbourg, l’article étudie la manière dont les résultats de l’examen, conservés dans des protocoles (1708-1790) et répondant à des logiques plurielles, entraînent des modulations du droit de maîtrise. L’examen apparaît alors non seulement comme un rituel légitimant la séparation maîtres/compagnons, mais comme un moment de classement au moins temporaire dans une hiérarchie entre maîtres
How will AI contribute to improving individual and global health?
No full textInternational audienceArtificial Intelligence (AI) applications add significant value to the health sector, such as DNA analysis, prediction models, radiotherapy personalization to avoid side effects, diagnostic evaluation, treatment recommendations, robotization of surgical operations, research advancements on rare diseases, and task automatization. This chapter will present a classification of all the contributions of AI to improving health in the world. To achieve this goal in the health sector, AI must respect regulations (future IA Act in Europe) and address several ethical challenges, such as patient consent to data collection and treatment, robustness and accuracy of the model, personal data privacy, explainability, and human oversight. Responsible AI in this sector is required to achieve a better world
Forward-Backward Binarization
No full textBinarization of gene expression data is a \textbf{critical prerequisite} for the synthesis of Boolean gene regulatory network (GRN) models from omics datasets. Because Boolean networks encode gene activity as binary variables, the accuracy of binarization directly conditions whether the inferred models can faithfully reproduce biological experiments, capture regulatory dynamics, and support downstream analyses such as controllability and therapeutic strategy design. In practice, binarization is most often performed using thresholding methods that partition expression values into two discrete levels, representing the absence or presence of gene expression. However, such approaches oversimplify the underlying biology: gene-specific functional roles, measurement uncertainty, and the scarcity of time-resolved experimental data render thresholding alone insufficient. To overcome these limitations, we propose a novel \textbf{regulation-based binarization method} tailored to snapshot data. Our approach combines thresholding with functional binary value completion guided by the regulatory graph, propagating values between regulators and targets according to Boolean regulation rules. This strategy enables the inference of missing or uncertain values and ensures that binarization remains biologically consistent with both regulatory interactions and Boolean modeling principles of the gene regulation. Validation against ODE simulations of artificial and established Boolean GRNs demonstrates that the method achieves accurate and robust binarization, thereby strengthening the reliability of Boolean network synthesis
A Novel Data-Driven Visualization and Analysis Framework for Embedded Robotic Firmware
No full textInternational audienceThe growing complexity of embedded firmware in robotics and automation, including mobile robots, industrial actuators, and autonomous systems, presents significant challenges related to maintainability, debugging, and efficient developer onboarding. Traditional documentation methods frequently become outdated and insufficient, which complicates code comprehension and increases the likelihood of errors. At the same time, current tools often provide only static or fragmented documentation without the interactive, realtime insights required for effective development. To address these limitations, we present a unified visualization and documentation approach based on the open-source tools Doxygen and Graphviz. When applied to a sophisticated embedded control board designed for robotic applications, this method generates interactive documentation, call graphs, and module dependency diagrams that enhance code comprehension, simplify debugging, and accelerate onboarding. In addition, the integration supports targeted optimization by highlighting performance bottlenecks and areas of excessive code complexity, thereby guiding data-driven refactoring. Overall, our findings demonstrate that automated, interactive visualization significantly improves maintainability and development efficiency in embedded software
A selective bottleneck during host entry drives the evolution of new plant symbionts
No full textInternational audienceThe acquisition of mobile genetic elements (MGEs) can trigger radical shifts in microbial lifestyles, for example by converting a mutualist into a pathogen or vice versa. These transitions often involve changes in host range, infection strategies, or ecological niches, which typically require specific adaptations to the different stages of the new life cycle. While comparative genomic studies have documented several MGE-associated lifestyle transitions, a detailed understanding of the tempo and mode of adaptation to new symbiotic lifestyles is still lacking.Here, we sought to evolve new nitrogen-fixing bacterial symbionts of the legume plant Mimosa pudica from an ancestral plant pathogenic bacterium, Ralstonia solanacearum, which was engineered with a plasmid carrying essential symbiosis genes. We experimentally evolved this strain for over 900 generations during serial passages through a simplified symbiotic life cycle (comprising rhizosphere inoculation, root entry, and within-plant proliferation) and characterized the dynamics of molecular and phenotypic adaptation in the evolved populations.Multiple independent lineages exhibited rapid and parallel fitness increase during their interaction with M. pudica. Whole-population sequencing revealed a continuous accumulation of mutations, facilitated by a plasmid-induced transient hypermutagenesis phase before host entry. We observed sequential sweeps of mutational cohorts, with multiple adaptive mutations co-occurring within these cohorts. Notably, all adaptive mutations enhanced host entry, while only a subset also improved within-host proliferation. Computational modelling suggests that this pattern is a consequence of the strong selective bottleneck occurring at host entry and immediately following the hypermutagenesis phase. Our findings highlight how selective bottlenecks shape adaptive trajectories of symbiotic bacteria experiencing complex infection processes
Cell penetrating peptides probed by nanopores
No full textInternational audienceWe examined whether the CPP model would be detected by dierent biological nanopores and compared these interactions to those with other peptide/nanopore systems. Remarkably, the CPP model exhibited drastic dierences. At transmembrane voltages as low as 2 mV, we observed reversible and well-resolved ionic conductance steps (current blockades) associated with the capture and release of single CPP molecules through Aerolysin (AL), alpha-Hemolysin (-HL), and CYtk nanopore never observed before. The CPP model enables partitioning into dierent nanopores whatever the sign of applied electrical force despite the high charge density of the CPP suggesting that thermal uctuation, electrophoresis, or electroosmosis enter in competition and can act as driving force depending on the applied electrical polarity and on the magnitude of the applied voltage. These results suggest that CPP molecules can penetrate a conned medium with a high energy barrier without the need for high voltages, likely due to specic features of CPPs such as their structure, sequence, charges, and anity with charged pores. The behavior of CPP model through Aerolysin nanopore is dierent according to the driving forces. A drastic dierence in the voltage-dependence of the interaction, never observed before, was observed when the CPP is driven electrphoretically, namely above -20 mV in magnitude the CPP is traped inside the the nanopore for an extended time before its release. More interestingly increasing applied voltage increases the traping time up to minutes which could be due to a combination of opposite driving forces and hydrophobic/electrostatic interactions between the amphipathic CPP and the nanopore. Our approach marks the rst step toward applications to screen various classes of peptides such as CPPs, fusion peptides, and others membranotropic peptides