Percolation transition in the porous structure of latex-templated silica monoliths

International audiencePorous sol-gel silica monoliths are prepared using PMMA nanoparticles, 60 nm in diameter, as sacrificial templates. The pore-structure of the calcined pellets is investigated through nitrogen adsorption to assess the evolution of the porosity when varying the amount of porogen. The latex templated monoliths present a well defined spherical extrinsic porosity and an intrinsic microporosity due to preparation process. As a result of a careful analysis of the adsorption hysteresis, we identify a percolation threshold of the spherical porosity around 30% volume fraction. This phenomenon, similar to the percolation previously observed in latex-templated silica films, opens the way to the use of latex-templated porous silica monoliths with a tailorable and reliable pore structure

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

International audienceThe development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by "RTK swapping" by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation

Combined drug action of 2-phenylimidazo[2,1-b]benzothiazole derivatives on cancer cells according to their oncogenic molecular signatures

The development of targeted molecular therapies has provided remarkable advances into the treatment of human cancers. However, in most tumors the selective pressure triggered by anticancer agents encourages cancer cells to acquire resistance mechanisms. The generation of new rationally designed targeting agents acting on the oncogenic path(s) at multiple levels is a promising approach for molecular therapies. 2-phenylimidazo[2,1-b]benzothiazole derivatives have been highlighted for their properties of targeting oncogenic Met receptor tyrosine kinase (RTK) signaling. In this study, we evaluated the mechanism of action of one of the most active imidazo[2,1-b]benzothiazol-2-ylphenyl moiety-based agents, Triflorcas, on a panel of cancer cells with distinct features. We show that Triflorcas impairs in vitro and in vivo tumorigenesis of cancer cells carrying Met mutations. Moreover, Triflorcas hampers survival and anchorage-independent growth of cancer cells characterized by 'RTK swapping' by interfering with PDGFRβ phosphorylation. A restrained effect of Triflorcas on metabolic genes correlates with the absence of major side effects in vivo. Mechanistically, in addition to targeting Met, Triflorcas alters phosphorylation levels of the PI3K-Akt pathway, mediating oncogenic dependency to Met, in addition to Retinoblastoma and nucleophosmin/B23, resulting in altered cell cycle progression and mitotic failure. Our findings show how the unusual binding plasticity of the Met active site towards structurally different inhibitors can be exploited to generate drugs able to target Met oncogenic dependency at distinct levels. Moreover, the disease-oriented NCI Anticancer Drug Screen revealed that Triflorcas elicits a unique profile of growth inhibitory-responses on cancer cell lines, indicating a novel mechanism of drug action. The anti-tumor activity elicited by 2-phenylimidazo[2,1-b]benzothiazole derivatives through combined inhibition of distinct effectors in cancer cells reveal them to be promising anticancer agents for further investigation

Engagement, souffrance, résilience : pour une histoire genrée de la guerre du Viêt-Nam: Conférence du cycle "Violences sexuelles et violences de genre dans le monde"

Fonds audiovisuel de l'INALCO, France, © 2023Après un survol historiographique sur l'histoire des Jeunesses de choc (Thanh Niên Xung Phong), nous partirons sur les pas de cette jeunesse mobilisée sur la Piste Hô Chi Minh. La commémoration en 2019 du 60e anniversaire de l’ouverture de la piste (mai 1959) a permis de réévaluer l’importance stratégique de ce réseau dans la victoire communiste de 1975. Cette “piste mythique” (đường mòn huyền thoại) s'est révélée être la clé de voûte de la guerre de réunification. L'expérience de dizaines de milliers de femmes et d’hommes pour ravitailler le front du Sud en forces et en munitions est aujourd'hui mieux connue et fait surgir les questions d'engagement, de souffrance et de résilience.L’expérience de la Piste sera considérée ici sous la double perspective de la marge et du genre. Le rôle essentiel des femmes sera souligné : démineuses, déblayeuses, conductrices de camion, chanteuses, éclaireuses, infirmières, miliciennes… , nous relierons entre-elles ces marges multi-situées de la guerre (jungles, villes, campagnes, diplomatie internationale) pour offrir une photographie plus générale du conflit du point de vue du genre. Il reste en effet une histoire de la guerre du Viêt-Nam à écrire dans une perspective genrée, en prenant en compte toutes ses composantes (nord et sud, marge et centre, ethnies minoritaires, fonctionnement genré de l’armée populaire, engagement des femmes des deux côtés du 17e Parallèle, populations civiles)

Engagement, souffrance, résilience : pour une histoire genrée de la guerre du Viêt-Nam<br>: Conférence du cycle "Violences sexuelles et violences de genre dans le monde"

Fonds audiovisuel de l'INALCO, France, © 2023Après un survol historiographique sur l'histoire des Jeunesses de choc (Thanh Niên Xung Phong), nous partirons sur les pas de cette jeunesse mobilisée sur la Piste Hô Chi Minh. La commémoration en 2019 du 60e anniversaire de l’ouverture de la piste (mai 1959) a permis de réévaluer l’importance stratégique de ce réseau dans la victoire communiste de 1975. Cette “piste mythique” (đường mòn huyền thoại) s'est révélée être la clé de voûte de la guerre de réunification. L'expérience de dizaines de milliers de femmes et d’hommes pour ravitailler le front du Sud en forces et en munitions est aujourd'hui mieux connue et fait surgir les questions d'engagement, de souffrance et de résilience.L’expérience de la Piste sera considérée ici sous la double perspective de la marge et du genre. Le rôle essentiel des femmes sera souligné : démineuses, déblayeuses, conductrices de camion, chanteuses, éclaireuses, infirmières, miliciennes… , nous relierons entre-elles ces marges multi-situées de la guerre (jungles, villes, campagnes, diplomatie internationale) pour offrir une photographie plus générale du conflit du point de vue du genre. Il reste en effet une histoire de la guerre du Viêt-Nam à écrire dans une perspective genrée, en prenant en compte toutes ses composantes (nord et sud, marge et centre, ethnies minoritaires, fonctionnement genré de l’armée populaire, engagement des femmes des deux côtés du 17e Parallèle, populations civiles)

Antifungal de-escalation was not associated with adverse outcome in critically ill patients treated for invasive candidiasis: post hoc analyses of the AmarCAND2 study data

International audiencePURPOSE: Systemic antifungal therapy (SAT) of invasive candidiasis needs to be initiated immediately upon clinical suspicion. Controversies exist about adequate time and potential harm of antifungal de-escalation (DE) in documented and suspected candidiasis in ICU patients. Our objective was to investigate whether de-escalation within 5 days of antifungal initiation is associated with an increase of the 28-day mortality in SAT-treated non-neutropenic adult ICU patients. METHODS: From the 835 non-neutropenic adults recruited in the multicenter prospective observational AmarCAND2 study, we selected the patients receiving systemic antifungal therapy for a documented or suspected invasive candidiasis in the ICU and who were still alive 5 days after SAT initiation. They were included into two groups according to the occurrence of observed SAT de-escalation before day 6. The average causal SAT de-escalation effect on 28-day mortality was evaluated by using a double robust estimation. RESULTS: Among the 647 included patients, early de-escalation at day 5 after antifungal initiation occurred in 142 patients (22 %), including 48 (34 %) patients whose SAT was stopped before day 6. After adjustment for the baseline confounders, early SAT de-escalation was the solely factor not associated with increased 28-day mortality (RR 1.12, 95 % CI 0.76-1.66). CONCLUSION: In non-neutropenic critically ill adult patients with documented or suspected invasive candidiasis, SAT de-escalation within 5 days was not related to increased day-28 mortality but it was associated with decreased SAT consumption. These results suggest for the first time that SAT de-escalation may be safe in these patient

Bonding and Electronic Structure in Consanguineous and Conjugal Iron and Rhenium sp Carbon Chain Complexes [MC 4 M‘] n + : Computational Analyses of the Effect of the Metal

International audienc

Systemic antifungal therapy for proven or suspected invasive candidiasis: the AmarCAND 2 study

International audienceBackground - In the context of recent guidelines on invasive candidiasis (IC), how French intensive care units (ICUs) are managing IC?Methods - This is a prospective observational multicenter cohort study. During 1 year (2012-2013), 87 French ICUs enrolled consecutive patients with suspected or proven IC (SIC or PIC) and receiving systemic antifungal therapy (SAT). Data were collected up to 28 days after inclusion.Results - We studied 835 patients, 291 with PIC and 544 with SIC. At SAT initiation, patients with SIC were significantly more severe (SAPS II 50.1 ± 18.7 vs. 46.2 ± 18.0). Severe sepsis or septic shock prompted to initiate empiric SAT in 70 % of SIC. Within 4 days in median, the initial SAT was modified in 49 % of patients with PIC vs. 33 % patients with SIC. Modifications were most often motivated by mycological results, and de-escalation was the most frequent change. Regarding compliance to IC management guidelines, echinocandin was used for 182 (62.5 %) patients with PIC, and 287 (52.7 %) of those with SIC; central venous catheter was removed in 87 (54.3 %) of patients with candidaemia, and 43 of the remaining patients received echinocandin; and de-escalation was undertaken after 5 days of SAT in 142 patients, after 10 days in 13 patients. As 20.6 % of SIC were secondarily documented, 403/835 (48 %) patients had finally a proven IC. Candida albicans was the main pathogen (65.3 %), then Candida glabrata (15.9 %). The 28-day mortality rates were 40.0 % in candidaemia, 25.4 % in cIAI, and 26.7 % in deep-seated candidiasis. In the overall population of patients with proven IC, four independent prognostic factors were identified: immunosuppression (Odds Ratio (OR) = 1.977: 1.03-3.794 95 % confidence interval (CI), p = 0.04), age (OR = 1.035; 1.017-1.053 95 % CI; p 46 on ICU admission (OR = 2.894; 1.81-4.626 95 % CI; p Conclusion - When SAT is initiated in French ICUs, the IC is ultimately proven for 48 % of patients. Empiric SAT is initiated in severely ill ICU patients. The initial SAT is often adapted, with de-escalation to fluconazole when possible. Mortality rate remains high.<br