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Gouverner le métabolisme portuaire : les relations socio-matérielles entre port et territoire à l’heure des transitions écologiques
No full textPort territories are inherently multi-scalar spaces positioned at the interface of the terrestrial and the maritime, the local and the global. Their evolution, profoundly shaped by the technological transformations of the 20th century, is often analyzed through the lens of a progressive disconnection between the port and its surrounding territory, leading to the invisibilisation of their structural and continuous interdependencies. In light of socio-ecological imperatives, the role of ports in territorial organization and the construction of collective imaginaries warrants reassessment. This thesis examines the socio-material relations between ports and territories and their role in shaping discourses and transition trajectories. Drawing on two case study areas—the Loire Estuary and the Los Angeles urban region—it develops a spatialised and politicised approach to the transformation of port territories. By analysing the materiality of port hinterlands and urbanization processes, this research highlights the interconnections that structure them and interrogates the implications of these shifting territorial metabolic relations in a context of escalating and interwoven ecological crises.Les territoires portuaires sont par nature des espaces multiscalaires situés à l’interface du terrestre et du maritime, du local et du global. Leur évolution, profondément marquée par les transformations technologiques du XXe siècle, est souvent analysée à travers le prisme d’une déconnexion progressive entre le port et son territoire, conduisant à l’invisibilisation de leurs interdépendances structurelles et continues. À la lumière des impératifs socio-écologiques, le rôle des ports dans l’organisation territoriale et la construction des imaginaires collectifs mérite d’être réévalué. Cette thèse explore les relations sociomatérielles entre ports et territoires et leur rôle dans la construction des discours et des trajectoires de transition. À partir de deux terrains d’étude — l’estuaire de la Loire et la région urbaine de Los Angeles —, elle développe une approche spatialisée et politisée des transformations des territoires portuaires. En examinant la matérialité des hinterlands portuaires et les processus d’urbanisation, cette recherche met en évidence les interconnexions qui les structurent et interroge les implications de ces reconfigurations métaboliques territoriales dans un contexte de crises écologiques multiples et croissantes
Pro-Reparative Effects of KvLQT1 Potassium Channel Activation in a Mouse Model of Acute Lung Injury Induced by Bleomycin
No full textInternational audienceAcute Respiratory Distress Syndrome (ARDS) is a complex and devastating form of respiratory failure, with high mortality rates, for which there is no pharmacological treatment. The acute exudative phase of ARDS is characterized by severe damage to the alveolar–capillary barrier, infiltration of protein-rich fluid into the lungs, neutrophil recruitment, and high levels of inflammatory mediators. Rapid resolution of this reversible acute phase, with efficient restoration of alveolar functional integrity, is essential before the establishment of irreversible fibrosis and respiratory failure. Several lines of in vitro and in vivo evidence support the involvement of potassium (K+) channels—particularly KvLQT1, expressed in alveolar cells—in key cellular mechanisms for ARDS resolution, by promoting alveolar fluid clearance and epithelial repair processes. The aim of our study was to investigate whether pharmacological activation of KvLQT1 channels could elicit beneficial effects on ARDS parameters in an animal model of acute lung injury. We used the well-established bleomycin model, which mimics (at day 7) the key features of the exudative phase of ARDS. Our data demonstrate that treatments with the KvLQT1 activator R-L3, delivered to the lungs, failed to improve endothelial permeability and lung edema in bleomycin mice. However, KvLQT1 activation significantly reduced neutrophil recruitment and tended to decrease levels of pro-inflammatory cytokines/chemokines in bronchoalveolar lavages after bleomycin administration. Importantly, R-L3 treatment was associated with significantly lower injury scores, higher levels of alveolar type I (HTI-56, AQP5) and II (pro-SPC) cell markers, and improved alveolar epithelial repair capacity in the presence of bleomycin. Together, these results suggest that the KvLQT1 K+ channel may be a potential target for the resolution of the acute phase of ARDS
Un passé dépassé ? Les mémoires protestantes des guerres de Religion (vers 1685-2022) [position de thèse]: Thèse d’histoire moderne et contemporaine, Le Mans Université, 2024, 639 p.
No full textAlors que les protestants français cultivent le souvenir de la Saint-Barthélemy depuis le XVIe siècle, le contexte des guerres de Religion (1562-1598), dans lequel s’inscrivent les célèbres massacres, semble beaucoup moins retenir leur attention. Or ces troubles civils et religieux représentent une crise majeure de l’histoire nationale et voient, pour la première fois, les protestants français prendre les armes en grand nombre. C’est tout l’objet de la thèse de Laurent Ropp, soutenue le 22 novembre 2024 à Le Mans Université, que de saisir, dans la longue durée, les mémoires de ces conflits dans les communautés issues de la Réforme. Des années 1680, marquées par une controverse interconfessionnelle sur les guerres de Religion, au 450e anniversaire de la Saint-Barthélemy (2022), cette recherche éclaire la manière dont le présent influence le souvenir des luttes du second XVIe siècle et examine dans quelle mesure ces conflits du passé restent d’actualité dans les siècles qui les ont suivis. Un vaste corpus imprimé, auquel s’ajoutent des sources plus originales, comme 526 réponses à un questionnaire en ligne, est mobilisé afin de rendre compte des réactivations mémorielles et de mettre au jour les continuités et les transformations des représentations et des usages des troubles. Centrée sur les réformés français tout en intégrant les luthériens et les évangéliques de l’Hexagone ainsi que les communautés protestantes de trois pays d’accueil de la diaspora huguenote, cette investigation offre également une réflexion sur l’unité et la pluralité des mémoires huguenotes
Aléas climatiques et conséquences sur les eaux destinées à la consommation humaine
No full textInternational audienceAmong the many identified impacts of climate change (CC), climate warming and the intensification of the hydrological cycle result in a higher transfer of contaminants (organic matter, pathogens, salts, emerging contaminants, etc.) from watersheds to water sources, and can lead to an increase in by-products (BPs)after disinfection treatment. In this article, various approaches are presented to assess the effects of climatic hazards and climate change on drinking water supplies. Levels of BPs (sum of 4 trihalomethanes-THM4) in distributed water were studied experimentally during rainfall events and by modelling according to different emission scenarios (Regional Concentration Pathway, RCP). Results show that the potential for the formation of BPs can be multiplied by 2.5 in a simulated distribution system during rain events. Moreover, the most pessimistic CC emission scenarios (RCP8.5) induce a significant increase in the probability of exceeding the THM4 threshold of 80 μg/L. Finally, a survey carried out among drinking water supply managers showed a significant link between the level of knowledge about CC and, on the one hand, the fact of having already experienced the impact of CC, and on the other, the priority given to adaptation and the use of decision-support tools for adaptation. These potential exposure modifications underline the importance of improving data acquisition on climate hazards, and of providing managers and decision-makers with relevant decision-support tools for improving adaptation.Parmi les nombreux impacts identifiés des changements climatiques (CC), le réchauffement climatique et l’intensification du cycle hydrologique entraînent un transfert plus important de contaminants (matières organiques, pathogènes, sels, contaminants émergents, etc.) des bassins versants vers les sources d’eau, et peuvent entraîner une augmentation des sous-produits (BP) après traitement de désinfection. Dans cet article, différentes approches sont présentées pour évaluer les effets des aléas climatiques et du changement climatique sur l’approvisionnement en eau potable. Les teneurs en BP (somme de 4 trihalométhanes-THM4) dans l’eau distribuée ont été étudiées expérimentalement lors d’événements pluvieux et par modélisation selon différents scénarios d’émission (Regional Concentration Pathway, RCP). Les résultats montrent que le potentiel de formation de BP peut être multiplié par 2,5 dans un système de distribution simulé lors d’épisodes de pluie. De plus, les scénarios d’émission de CC les plus pessimistes (RCP8.5) induisent une augmentation significative de la probabilité de dépasser le seuil de THM4 de 80 μg/L. Enfin, une enquête menée auprès des gestionnaires d’approvisionnement en eau potable a montré un lien significatif entre le niveau de connaissance des CC et, d’une part, le fait d’avoir déjà expérimenté l’impact des CC, et d’autre part, la priorité donnée à l’adaptation et à l’utilisation d’outils d’aide à la décision pour l’adaptation. Ces modifications potentielles de l’exposition soulignent l’importance d’améliorer l’acquisition de données sur les aléas climatiques, et de fournir aux gestionnaires et aux décideurs des outils d’aide à la décision pertinents pour améliorer l’adaptation
Survival outcomes and response to immune checkpoint inhibitors among patients with advanced Merkel cell carcinoma: a retrospective study of 81 patients
No full textInternational audienceBackground: Advanced Merkel cell carcinoma (MCC) has been shown to be effectively targeted by PD-1/PD-L1 inhibitors in phase II trials and real-world studies. More than 50% of MCC patients display resistance to PD-1/PD-L1 inhibitors while identification of predictive factors for response has been inconclusive so far in this population. Our primary objective was to assess overall survival (OS) in a real-world cohort of advanced MCC patients treated with PD(L)1 inhibitors in France. Secondary objectives were to assess real-world overall response rates (rwORR), duration of response (rwDOR), progression-free survival (rwPFS) and predictive factors of response.Methods: Patients from an ongoing cohort of MCC cases (1998-2023) were included in the current study if they had received at least one infusion of PD-1/PD-L1 inhibitor for advanced MCC as any line of treatment.Results: Among the 81 patients included, OS at 24 months- was 58 % (95 % confidence interval (CI) 46.2-68.9). RwORR was 51.9 % (95 %CI 40.9-62.9). Median OS was significantly higher among responders than non-responders (median OS 59.0 months (95 %CI 39.4-not reached (NR)) vs. 8.1 months (95 %CI 6.6-17.0). RwDOR was significantly shorter in partial vs. complete responders (3.4 months vs. NR). Patients with rwDOR in excess of 6 months had improved OS compared to others (median OS: 59.0 months, 95 %CI 39-NR vs. 28.5 months, 95 %CI 20.3-NR). Median rwPFS was 9.0 months (95 %CI 4.5-20.4). None of the baseline clinical and laboratory characteristics or treatment-related characteristics were found to be associated with response.Conclusion: Our results confirm durable responses and prolonged survival to PD-1/PD-L1 inhibitors in MCC patients. We did not identify any biomarker predictive of response to treatment. Our data underline the benefit of achieving complete response in PD(L)1 inhibitor-treated MCC patients, allowing longer duration of response and increased OS, suggesting the potential use of DOR above 6 months as a surrogate marker of OS in this setting
Including everyday mobility with agent-based models in the assessment of critical areas of noise exposure
No full textInternational audienceIdentifying urban areas that concentrate critical noise exposures is a fundamental step in formulating noise action plans for protecting public health. Standard European assessments that guide this identification are based on residential exposure to noise, neglecting everyday mobility. There is growing interest in noise assessment using agent-based exposure models to address this limitation. This approach aims to simulate a daily activity plan for each individual in a modeled population to estimate their trajectories. Based on the mobility pattern of the population, transport-related noise emissions and propagation are modeled. Then, the exposure profile of each agent is estimated. This study uses this framework to investigate how mobility shapes noise exposure across activity contexts, social groups, and time of the day. A case study on Lyon and Villeurbanne cities shows that a residential exposure assessment can lead to a 10% underestimation of critical exposure occurrences compared to a mobility-based assessment. Beyond the total number of occurrences, activity contexts of exposure evolve during the day, with relevant critical exposure areas emerging concerning work and study activities. Regarding target group analysis, for young agents, exposure mitigation in educational settings has the potential to reduce critical exposure occurrences by nearly half. Further, the study analyzes the relationships between short-term and daily dose exposures and reviews the definition of critical exposure periods adapted to specific life rhythms. Future research should focus on noise impact assessments for context-specific exposures and the translation of critical area analysis into noise management strategies
NanoPULSE: The first micromixer method delivering consistent lipid nanoparticle formulations seamlessly across all scales
No full textInternational audienceThe development of RNA-based therapies and vaccines formulated with lipid nanoparticles (LNPs) is currently hindered by the lack of a formulation technology that supports seamless scalability—from microliter-scale screening to multi-liter production. Current scale-up strategies require transitioning between incompatible mixing techniques, such as microfluidics for low-volume R&D production and T-mixing or impingement jet mixing (IJM) at large-scale. These transitions introduce variability in critical LNP quality attributes, including size, polydispersity index (PDI), encapsulation efficiency (EE%), and morphology. Such inconsistencies directly impact the efficacy, toxicity and biodistribution of the final drug product hence leading to prolonged development timelines, increased costs, and a high risk of failure during tech transfer. We present NanoPULSE, a patented micromixing technology designed to bridge this scalability gap and enable the consistent formulation of identical nanoparticles and RNA-LNPs at any production scale. The system uses high-frequency valves to sequentially inject aqueous and organic phases into an optimized T-junction, enhancing mixing efficiency based on the Taylor-Aris dispersion principle. This method ensures robust and uniform mixing for LNP formulation independent of volume. First, numerical Lagrangian simulations were conducted to evaluate the impact of mixing parameters on nanoparticle characteristics and to optimize the channel geometry. These simulations led to the development of a novel metric for quantifying NanoPULSE’s mixing efficiency. Experimental validation using multi-angle dynamic light scattering (MADLS) demonstrated that both empty and RNA-loaded LNPs maintain consistent sizes and low PDI values (below 0.2) across a broad range of production volumes, from 500 µL to 4 L. Encapsulation efficiency, yield, and structural morphology were assessed and showed to be consistent and comparable to, or better than, state-of-the-art microfluidic systems. NanoPULSE was shown to enable fine control over LNP size by adjusting the injection frequency, all while using a single formulation recipe. The close alignment between experimental results and simulation predictions reinforces the connection between mixing dynamics and nanoparticle properties. Together, these findings establish NanoPULSE as a robust, scalable, and reproducible platform for RNA-LNP production, with direct implications for accelerating RNA drug development and facilitating industrial translation
Une nouvelle approche au problème des valeurs propres pour l'opérateur de Monge-Ampère
No full textWe study the eigenvalue problem for the complex Monge-Ampère operator in bounded hyperconvex domains in C^n , where the right-hand side is a non-pluripolar positive Borel measure. We establish the uniqueness of eigenfunctions in the finite energy class introduced by Cegrell, up to positive multiplicative constants, and provide a Rayleigh quotient type formula for computing the eigenvalue. Under a natural continuity assumption on the measure, we further show that both the eigenvalue and eigenfunctions can be obtained via an iterative procedure starting from any negative finite energy function. Our approach relies on the fine properties of plurisubharmonic envelopes, which allow a partial sublinearization of the nonlinear problem. As far as we know, this method is new, even in the linear case, and not only yields new results but also significantly simplifies existing arguments in the literature. Moreover, it extends naturally to the setting of complex Hessian operators. Finally, by translating our results from the complex Monge-Ampère setting via a logarithmic transformation, we also obtain several interesting analogues for the real Monge-Ampère operator.Nous étudions le problème des valeurs propres pour l'opérateur complexe de Monge-Ampère dans les domaines hyperconvexes bornés en C^n , où le membre droite est une mesure de Borel positive non multipolaire. Nous établissons l'unicité des fonctions propres dans la classe d'énergie finie introduite par Cegrell, à constantes multiplicatives positives près, et fournissons une formule de type quotient de Rayleigh pour le calcul de la valeur propre. Sous une hypothèse de continuité naturelle sur la mesure, nous montrons en outre que la valeur propre et les fonctions propres peuvent être obtenues par une procédure itérative à partir de toute fonction d'énergie finie négative. Notre approche s'appuie sur les propriétés fines des enveloppes plurisubharmoniques, qui permettent une sous-linéarisation partielle du problème non linéaire. À notre connaissance, cette méthode est nouvelle, même dans le cas linéaire, et non seulement produit de nouveaux résultats, mais simplifie aussi considérablement les arguments existants dans la littérature. De plus, il s'étend naturellement au cadre des opérateurs hessiens complexes. Enfin, en traduisant nos résultats du cadre complexe de Monge-Ampère via une transformation logarithmique, nous obtenons également plusieurs analogues intéressants pour le véritable opérateur de Monge-Ampère
Potential risk of cross-resistance to voriconazole in HIV/AIDS patients with Talaromyces marneffei infection and the mechanisms of the cross-resistance
No full textInternational audienceAbstract Background The use of fluconazole for long-term oral candidiasis treatment in HIV/AIDS patients can potentially affect the clearance rate and antifungal efficacy of voriconazole against Talaromyces marneffei infection. We isolated two T. marneffei strains that were both resistant to fluconazole and voriconazole. To investigate the mechanism underlying the induction of the cross-resistance in T. marneffei. Methods Fluconazole-resistant strains were induced in vitro. The target enzyme 14-α sterol demethylase Cyp51B was sequenced, and drug efflux pump expression was determined by RT–qPCR in all strains. Results The sensitivity of fluconazole-induced resistant strains to fluconazole was greater than 128 mg/L, and this resistance was stably inherited after fluconazole pressure was removed. MICs of voriconazole for resistant strains were 4∼16 times greater than FRR (0.25–1 versus 0.06 mg/L). Two mutation hotspots in Cyp51B were detected: G441D and G441V. The AtrF, Mdr1 and Pmfcz genes were significantly overexpressed in the vast majority of the fluconazole-resistant strains (P < 0.05). Conclusions The growth of T. marneffei in the presence of fluconazole could induce voriconazole resistance in vitro. The main cause of this cross-resistance in T. marneffei appears to be related to a mutation in Cyp51B at G441 and overexpression of the efflux pumps AtrF, Mdr1 and Pmfcz
