HAL Université de Toulouse, et Toulouse INP
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Novel drugs approved by the EMA, the FDA and the MHRA in 2024: A year in review
No full textInternational audienceIn the past year, the European Medicines Agency (EMA), the Food and Drug Administration (FDA) and the Medicines and Healthcare Products Regulatory Agency (MHRA) authorised 53 novel drugs. While the 2024 harvest is not as rich as in 2023, when 70 new chemical entities were approved, the number of ‘orphan’ drug authorisations in 2024 (21) is similar to that of 2023 (24), illustrating the dynamic development of therapeutics in areas of unmet need. The 2024 approvals of novel protein therapeutics (15) and advanced therapy medicinal products (ATMPs, 6) indicate a sustained trend also noticeable in the 2023 new drugs reviewed in this journal last year (16 and 11, respectively). Clearly, the most striking characteristic of the 2024 drug yield is the creative pharmacological design, which allows these medicines to employ a novel approach to target a disease. Some notable examples are the first drug successfully using a ‘dock‐and‐block’ mechanism of inhibition (zenocutuzumab), the first approved drug for schizophrenia designed as an agonist of M 1 /M 4 muscarinic receptors (xanomeline), the first biparatopic antibody (zanidatamab), binding two distinct epitopes of the same molecule, the first haemophilia therapy that instead of relying on external supplementation of clotting factors, restores Factor Xa activity by inhibiting TFPI (marstacimab), or the first ever authorised direct telomerase inhibitor (imetelstat) that reprogrammes the oncogenic drive of tumour cells. In addition, an impressive percentage of novel drugs were first in class (28 out of 53 or 53% of the total) and a substantial number can be considered disease agnostic, indicating the possibility of future approved extensions of their use for additional indications. The 2024 harvest demonstrates the therapeutic potential of innovative pharmacological design, which allows the effective targeting of intractable disorders and addresses crucial, unmet therapeutic needs
Source‐to‐Sink Signal Propagation in a Small, Coupled Catchment‐Deep‐Sea Fan System: The Sithas Example From the Corinth Rift (Pleistocene, Greece)
No full textInternational audienceQuantifying sediment fluxes is an essential part of the Source‐to‐Sink approach in the understanding of sedimentary systems. However, the transfer of sediment from the source to the sink and the factors controlling it are still poorly understood. We focus on a small catchment coupled with its offshore deep‐sea fan: the Sithas system (Gulf of Corinth, Greece). We restore the volume of sediment eroded in the catchment using geomorphic constraints; quantify the volume of sediment deposited in the offshore basin, after revising the age model; and calculate erosional fluxes using the BQART model. This allows for the comparison of the reconstructed fluxes of sediment eroded and deposited since 800 ka across the entire source‐to‐sink system. For the Sithas coupled catchment‐deep‐sea fan system, we show an increase in sedimentary fluxes both in erosion and deposition since 800 ka and particularly since 400 ka, where cyclic variations of ~120 kyr are recorded in erosion and deposition compartments. We suggest that the overall increase in flux results from a change in the catchment size due to the tectonic evolution of the region. The record of cyclic variations from 400 kyr in fluxes matches with the maturity of the system and with the intensification of glacial cycles and tectonic constraints migration. We also suggest that the discrepancy between erosion and deposition reflects a temporary storage between source and sink areas, probably along the coast. This has changed since 30 ka, introducing the last phase of evolution characterised by phased source and sink dynamics, suggesting a lack of temporary storage and a connection between river outlet and submarine canyon head. This study shows that sediment fluxes are controlled by the catchment's size as well as by climatic and tectonic factors and that even a small sedimentary system can be affected by temporary sediment storage
La digitalisation de l’agriculture: une trajectoire désirée, imposée ou contestée ?
No full textInternational audienceDans de nombreux discours, le développement des technologies numériques promet un avenir meilleur pour les agriculteurs et agricultrices, ainsi que des bénéfices pour la société dans son ensemble (Lajoie-O’Malley et al., 2020). Au-delà des discours, l’agriculture numérique mobilise des acteurs ainsi que des ressources publiques et privées. Le développement du numérique, comme tout changement technologique, implique une transformation multi-dimensionnelle, un ensemble de coévolutions technologiques et institutionnelles (Perez, 1983). Il s’inscrit dans des paradigmes et trajectoires technologiques, influencé par des mécanismes économiques de sélection et de verrouillage (Arthur, 1989; Nelson and Winter, 1982), ainsi que dans des systèmes d’innovation, structurés par des rapports de pouvoir (Amable, 2005; Dockès, 1990). Cette transformation se matérialise par une diversité de réalités, d’usages et d’effets qui viennent eux-mêmes jouer sur la trajectoire technologique (Mahoney and Thelen, 2009). Les usages sont vus ici comme la rencontre de visions (de pratiques, d’organisation du travail, d’objectifs) matérialisées dans des technologies et les institutions qui cadrent leurs usages, et la singularité des pratiques des acteurs et de leur contexte de travail environnemental, socio-économique et technologique.L’objectif de cette communication est de montrer comment se matérialisent, se mettent en place, se négocient ces co-évolutions technologiques et institutionnelles, liées au numérique agricole, dans les pratiques individuelles.Ce travail se base sur des entretiens réalisés avec 98 agriculteurs ayant des grandes cultures en Occitanie. Le terrain a été réalisé en recherchant une diversité de modèles d’exploitation (taille, engagement dans la transition écologique etc.).Les résultats montrent comment le développement du numérique est à la fois :i)Imposé aux agriculteurs, contraints par un ensemble de régulations publiques et privées, dans une logique de contrôle et de surveillance, de standardisation mais aussi d' « écologie de la justification » ii)Désiré voire promu par des professionnels en quête d’un avenir meilleur, pour améliorer les conditions de travail, la qualité du travail, et les performances économiques.iii)Contesté sur des aspects techniques, économiques, politiques ou environnementaux – par des agriculteurs qui défendent d’autres trajectoires sectoriellesCes résultats montrent une hétérogénéité de perceptions, qui révèle des dynamiques institutionnelles et des tensions associées, notamment liées à la manière dont le numérique joue sur les rapports de pouvoir au sein des filières
A Large-Scale Study of Binding Communication to Promote Ecological Behavior: The Commitment Technique Combined with Persuasive Communication in Mass Media Streaming
No full textInternational audienceThe climate emergency necessitates the adoption of effective communication strategies. While persuasive communication is easily scalable, its effectiveness at changing behavior is limited. In contrast, commitment techniques, such as foot-in-the-door and low-ball techniques, are more effective for behavior change but harder to scale. In this study, we test the effectiveness of combining a commitment strategy with persuasive communication in the streaming broadcast of an audiovisual show. Study 1, conducted in an "as if" setting with a full experimental design (N = 1003), showed that incorporating a commitment strategy into persuasive communication effectively promoted pro-ecological behavior, although it did not lead to a significant change in attitudes. In Study 2, conducted in an ecological setting during a live broadcast of an international rugby tournament (N = 240,245), we showed that combining commitment and persuasive strategies increased the intention to engage in behaviors that reduce digital pollution
Estimation des émissions de CO2 des applications et plateformes distribuées avec SimGrid/Batsim
No full textThis work presents a carbon footprint plugin designed to extend the capabilities of the Batsim simulator by allowing the calculation of CO2 emissions during simulation runs. The goal is to comprehensively assess the environmental impact associated with task and resource management strategies in data centers. The plugin is developed within SimGrid---the underlying simulation framework of Batsim---and computes carbon emissions based on the simulated platform's energy consumption and carbon intensity factor of the simulated machines. Once implemented, it is integrated into Batsim, ensuring compatibility with existing simulation workflows and enabling researchers to assess the carbon efficiency of their scheduling strategies
Bounding the WCET of a GPU Thread Block with a Multi-Phase Representation of Warps Execution
No full textInternational audienceThis paper proposes to model the Worst-Case Execution Time (WCET) of a GPU thread block as the Worst-Case Response Time (WCRT) of the warps composing the block. Inspired by the WCRT analyzes for classical CPU tasks, the response time of a warp is modeled as its execution time in isolation added to an interference term that accounts for the execution of higher priority warps. We provide an algorithm to build a representation of the execution of each warp of a thread block that distinguishes phases of execution on the functional units and phases of idleness due to operations latency. A simple formula relying on this model is then proposed to safely upper bound the WCRT of warps scheduled under greedy policies such as Greedy-Then-Oldest (GTO) or Loose Round-Robin (LRR). We experimented our approach using simulations of kernels from a GPU benchmark suite on the Accel-Sim simulator. We also evaluated the model on a GPU program that is likely to be found in safety critical systems : SGEMM (Single-precision GEneral Matrix Multiplication). This work constitutes a promising first building block of an analysis pipeline for enabling static WCET computation on GPUs
Worldwide analysis of microRNA polymorphism variability in domestic goa
No full textInternational audienceMicroRNAs (miRNAs) are a type of small non-coding RNAs involved in the post-transcriptional repression of target mRNA transcripts, and responsible for the fine-tuning of numerous molecular mechanisms regulating cell metabolism. The presence of single nucleotide polymorphisms (SNP) in miRNA genes is known to affect their expression dynamics and binding affinity toward targeted mRNAs, thus potentially modifying gene regulatory networks. Since domestication, goats have spread worldwide adapting to diverse environmental conditions. However, a comprehensive analysis of how evolutionary forces across and within continental regions have influenced the genome-wide distribution of miRNA polymorphisms in domestic goats is still lacking. By using whole-genome sequencing data from 1,059 domestic goats with African, Asian, American and European origins, we have identified SNPs located within and around goat miRNA genes. In doing so, we have found that miRNA SNPs display very low alternative allele frequencies (median alternative allele frequency of 0.38%) and that the distribution of SNPs within and around miRNA genes is uneven. Remarkably, the stem, loop and neighboring regulatory regions of precursor miRNA hairpins show a significantly higher SNP density compared with the miRNA seed, which determines the binding affinity to target mRNAs. This outcome is probably explained by the occurrence of strong purifying selection removing polymorphisms with potential effects on gene regulatory networks linked to miRNA function. Moreover, we have detected a differential segregation of miRNA SNPs across and within continental regions, with an enriched segregation of putatively high impact polymorphisms, i.e., those located in the seed and other biologically relevant regions of miRNA genes, in isolated goat populations with a low census and reduced heterozygosity. Such information could be useful to investigate the phenotypic consequences of miRNA polymorphisms disrupting gene regulatory networks in domestic goats, as well as to assess their potential impact on adaptation and fitness
Entanglement in cyclic sign invariant quantum states
No full textWe introduce and study bipartite quantum states that are invariant under the local action of the cyclic sign group. Due to symmetry, these states are sparse and can be parameterized by a triple of vectors. Their important semi-definite properties, such as positivity and positivity under partial transpose (PPT), can be simply characterized in terms of these vectors and their discrete Fourier transforms. We study in detail the entanglement properties of this family of symmetric states, showing in particular that it contains PPT entangled states. For states that are diagonal in the Dicke basis, deciding separability is equivalent to a circulant version of the complete positivity problem. We provide some geometric results for the PPT cone, showing in particular that it is polyhedral. In local dimension less than 5, we completely characterize these sets and construct entanglement witnesses; some partial results are also obtained for d = 6, 7. Finally, we initiate the study of cyclic sign covariant quantum channels, showing in particular that the PPT squared conjecture holds for some of these maps
SVEPM 2024, the annual conference of the Society for Veterinary Epidemiology and Preventive Medicine, Uppsala, Sweden
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P2NIA: Privacy-Preserving Non-Iterative Auditing
No full textInternational audienceUnlabelled - This study aimed to develop a practical, economically viable solution for treating hazardous landfill leachate using Pipe Freeze Crystallization (PFC) technology. The objective was to concentrate and solidify leachate from an effluent treatment plant processing approximately 8750 m annually, achieving resource recovery and environmental compliance. A 300 L h cooling demonstration plant was designed and implemented, incorporating a chiller, a secondary refrigerant mixture (40% ethylene glycol and 60% water), a clarifier, a reactor, and pumps. Μodelling with OLI software estimated recovery rates for salt and ice, providing a basis for operational adjustments. Leachate samples (2000 L) and concentrate (1000 L) were processed to evaluate the plant's performance in recovering clean water and NaSO. Experimental results confirmed the model predictions, with 302 L of concentrate yielding 102.9 kg of NaSO over 6 h and 273 L of leachate producing 118.7 kg of high-purity ice over 5.5 h. The energy consumption was measured at 171 kWh t of ice, aligning with theoretical predictions for a coefficient of performance of 1. These results validate the efficiency and feasibility of PFC in resource recovery. This study highlights the importance of PFC as a low-cost, energy-efficient technology for hazardous leachate treatment. Its scalability and ability to recover valuable resources such as NaSO and clean water present a sustainable alternative to conventional methods, contributing to zero-waste management goals in waste treatment practices. Supplementary information - The online version contains supplementary material available at 10.1007/s40710-025-00757-3