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International audience; Small molecules targeting the PD-1/PD-L1 checkpoint are actively searched to complement the anticancer arsenal. Different molecular scaffolds have been reported, including phenyl-pyrazolone derivatives which potently inhibit binding of PD-L1 to PD-1. These molecules are structurally close to antioxidant drug edaravone (EDA) used to treat amyotrophic lateral sclerosis. For this reason, we investigated the capacity of five PD-L1-binding phenyl-pyrazolone compounds (1–5) to scavenge the formation of oxygen free radicals using electron spin resonance spectroscopy with DPPH/DMPO probes. In addition, the reactivity of the compounds toward the oxidized base 5-formyluracil (5fU) was assessed using chromatography coupled to mass spectrometry and photodiode array detectors. The data revealed that the phenyl-pyrazolone derivatives display antioxidant properties and exhibit a variable reactivity toward 5fU. Compound 2 with a N-dichlorophenyl-pyrazolone moiety cumulates the three properties, being a potent PD-L1 binder, a robust antioxidant and an aldehyde-reactive compound. On the opposite, the adamantane derivative 5 is a potent PD-L1 binding with a reduced antioxidant potential and no aldehyde reactivity. The nature of the substituent on the phenyl-pyrazolone core modulates the antioxidant capacity and reactivity toward aromatic aldehydes. The molecular signature of the compound can be adapted at will, to confer additional properties to these PD-L1 binders.

International audience

International audience; The present paper is part of a two-fold study focused on cabin noise conducted within the frame of the Canoble project of the EU's CleanSky2 programme. The turbulent boundary layer developing on the fuselage creates excitation through wall pressure fluctuations that are, to some extent, transmitted and radiated inside the cabin, contributing to a significant part of the noise during cruise. Many studies have looked into the properties and structures of wall pressure fluctuations beneath a turbulent boundary layer, however there is still a lack of knowledge for some of their components and on the effect of pressure gradients, more so on realistic geometries. Hot-wires and hot-films have been used to characterise the boundary layer while newly developed antennas of digital MEMS microphones served for the measurement of wall pressure. The latter technology had previously been tested in duct flow by some of the authors and was able to isolate acoustic components from the hydrodynamic ones. The microphones themselves are embedded into a circuit board which reduces the overall thickness to only a few millimetres, and enables the measurements to be carried out without intrusive modification of the fuselage. Such an approach opens the door to in-flight tests in the future. These measurements have been performed on a scale-one mock-up of the fore part of a Dassault Aviation business jet, in an industrial-size wind tunnel. The boundary layer parameters along with the wall pressure spectra that were successfully measured will serve as inputs for the second part focusing on vibrational behaviour and noise radiation inside the cabin © Proceedings of the 26th International Congress on Sound and Vibration, ICSV 2019. All rights reserved.

International audience; Purpose: TE1PA is a C-functionalized monopicolinate cyclam designed for 64-copper chelation. It was proven to have excellent Cu(II) and Cu(I) chelation properties, with fast kinetics, high thermodynamic stability and resistance to transchelation in vitro, and a usefulness for phenotypic imagery when coupled to antibodies. This work presents in vivo studies (biodistribution, metabolism and imaging) of TE1PA in a syngenic multiple myeloma model on mice, compared to DOTA, its main competitor. Materials and methods: p-SCN-Bn-TE1PA and DOTA-NHS ester were grafted on 9E7.4 rat IgG2a antibody, targeting murine CD-138. Immunoconjugates were then radiolabelled with 64Cu. Both 64Cu-9E7.4-p-SCN-Bn-TE1PA and 64Cu-9E7.4-NHS-DOTA were injected in 12 mice previously grafted with 5T33 cells, allowing the development of subcutaneous tumors expressing CD-138. Each mouse was injected with 100 μg of radioimmunoconjugates corresponding to 10 MBq of 64Cu. For each time studied (2h, 24h and 48h post-injection), a biodistribution and a liver metabolism studies were conducted on mice for both radiolabelled antibodies. Additionally, a micro-PET scan was performed on 4 mice injected with 64Cu-9E7.4-p-SCN-Bn-TE1PA at those 3 times. Results: Biodistribution study shows an excellent hepatic clearance of the 64Cu-9E7.4-p-SCN-Bn-TE1PA over time. Significantly higher radioactivity was found in blood, lungs and heart at 48h PI for 64Cu-9E7.4-NHS-DOTA, which suggests a release of 64Cu from antibody, in parallel with a higher intestinal elimination. This was correlated by the liver metabolism study, which shows a better in vivo resistance to transchelation for 64Cu-9E7.4-p-SCN-Bn-TE1PA. The imaging study of 64Cu-9E7.4-p-SCN-Bn-TE1PA shows an increasing targeting of the tumors over time and confirms the hepatic clearance at 24h and 48h PI. Conclusion: 64Cu-9E7.4-p-NCS-Bn-TE1PA has shown a very high tumor targeting, associated to an increasing of tumor-to-tissues ratio over time that suggests an overall clearance from healthy tissues. Compared to DOTA, TE1PA displays an in vivo stability and resistance to transchelation significantly superior. This confirms the previous results obtained in vitro and 64Cu-labelled TE-1PA proved once again its usefulness for immuno-PET imaging in a preclinical model.

We propose and verify methods based on the slip-spring (SSp) model [ Macromolecules 2005, 38, 14] for predicting the effect of any monodisperse, binary, or ternary environment of topological constraints on the relaxation of the end-to-end vector of a linear probe chain. For this purpose we first validate the ability of the model to consistently predict both the viscoelastic and dielectric response of monodisperse and binary mixtures of type A polymers, based on published experimental data. We also report the synthesis of new binary and ternary polybutadiene systems, the measurement of their linear viscoelastic response, and the prediction of these data by the SSp model. We next clarify the relaxation mechanisms of probe chains in these constraint release (CR) environments by analyzing a set of “toy” SSp models with simplified constraint release rates, by examining fluctuations of the end-to-end vector. In our analysis, the longest relaxation time of the probe chain is determined by a competition between the longest relaxation times of the effective CR motions of the fat and thin tubes and the motion of the chain itself in the thin tube. This picture is tested by the analysis of four model systems designed to separate and estimate every single contribution involved in the relaxation of the probe’s end-to-end vector in polydisperse systems. We follow the CR picture of Viovy et al. [ Macromolecules 1991, 24, 3587] and refine the effective chain friction in the thin and fat tubes based on Read et al. [ J. Rheol. 2012, 56, 823]. The derived analytical equations form a basis for generalizing the proposed methodology to polydisperse mixtures of linear and branched polymers. The consistency between the SSp model and tube model predictions is a strong indicator of the compatibility between these two distinct mesoscopic frameworks.

We propose and verify methods based on the slip-spring (SSp) model [ Macromolecules 2005, 38, 14 ] for predicting the effect of any monodisperse, binary, or ternary environment of topological constraints on the relaxation of the end-to-end vector of a linear probe chain. For this purpose we first validate the ability of the model to consistently predict both the viscoelastic and dielectric response of monodisperse and binary mixtures of type A polymers, based on published experimental data. We also report the synthesis of new binary and ternary polybutadiene systems, the measurement of their linear viscoelastic response, and the prediction of these data by the SSp model. We next clarify the relaxation mechanisms of probe chains in these constraint release (CR) environments by analyzing a set of "toy" SSp models with simplified constraint release rates, by examining fluctuations of the end-to-end vector. In our analysis, the longest relaxation time of the probe chain is determined by a competition between the longest relaxation times of the effective CR motions of the fat and thin tubes and the motion of the chain itself in the thin tube. This picture is tested by the analysis of four model systems designed to separate and estimate every single contribution involved in the relaxation of the probe's end-to-end vector in polydisperse systems. We follow the CR picture of Viovy et al. [ Macromolecules 1991, 24, 3587 ] and refine the effective chain friction in the thin and fat tubes based on Read et al. [ J. Rheol. 2012, 56, 823 ]. The derived analytical equations form a basis for generalizing the proposed methodology to polydisperse mixtures of linear and branched polymers. The consistency between the SSp model and tube model predictions is a strong indicator of the compatibility between these two distinct mesoscopic frameworks. © 2017 American Chemical Society.

Ovarian cancer is usually diagnosed at an advanced stage with peritoneal extension which often occurs early on. Imaging plays an important role in the pretherapeutic assessment of peritoneal extension. Carcinomatosis involving the hepatic hilum, the cavo-supra-hepatic confluence, the mesentery, and/or the intestinal wall precludes optimal surgery and may be an indication for neoadjuvant chemotherapy. Abdominal and pelvic MDCT scan is the best imaging technique for the preoperative staging of peritoneal carcinomatosis. MRI can be useful in some cases. Conventional imaging however sometimes underestimates peritoneal carcinomatosis and therefore cannot always be a substitute for surgical staging.

Conventional treatment of high-grade glioma includes maximal surgical resection followed by external radiation therapy. Despite this treatment, the prognosis for patients is poor. High doses of chemotherapy might be another way to increase the response rate and median survival. Increasing doses of BCNU might be more effective, but also provokes unacceptable myelotoxicity. This dose-limiting toxicity can be circumvented by using autologous blood stem cell rescue. We report our experience of high-dose BCNU followed by transplantation of autologous hematopoietic stem cells in 114 patients with high-grade gliomas. Of the 114 gliomas, 78 were glioblastoma multiforme (GM) (68%), 24 anaplastic astrocytomas (AA) (21%), and 12 anaplastic oligodendrogliomas (OD) (11%). Complete surgical resection was performed for 22 patients (18 GM and 4 AA). The median age was 44 years (range 17-65). A total of 84 patients received autologous hematopoietic stem cells from bone marrow harvest, while 30 patients received granulocyte colony-stimulating factor followed by apheresis and received peripheral blood progenitor cells (PBPC). High dose of BCNU (800 mg/m(2)) was given at least 1 month after neurosurgery. Bone marrow or PBPC was transplanted 48-72 h after chemotherapy. Radiotherapy was started approximately 40 days after transplantation to a total of 60 Gy. Median follow-up was 89 months (19-163). The overall survival (OS) was, respectively, 12 months for GM, 37 months for OD and 81 months for AA. Histological type appeared to be the main discriminating factor, with a worse prognosis for GM. Within the GM population, age, completeness of surgery, and response appeared to be one important prognostic factors. The AA and OD populations were small to reliably assess prognostic factors. On multivariate analysis, the main prognostic factors were histologic type, quality of surgery, and age (P

In this paper, we exploit the stochastic slip-spring model to quantitatively predict the stress relaxation dynamics of star/linear blends with well-separated longest relaxation times and we analyze the results to assess the validity limits of the two main models describing the corresponding relaxation mechanisms within the framework of the tube picture (Doi's tube dilation and Viovy's constraint release by Rouse motions of the tube). Our main objective is to understand and model the stress relaxation function of the star component in the blend. To this end, we divide its relaxation function into three zones, each of them corresponding to a different dominating relaxation mechanism. After the initial fast Rouse motions, relaxation of the star is dominated at intermediate times by the "skinny" tube (made by all topological constraints) followed by exploration of the "fat" tube (made by long-lived obstacles only). At longer times, the tube dilation picture provides the right shape for the relaxation of the stars. However, the effect of short linear chains results in time-shift factors that have never been described before. On the basis of the analysis of the different friction coefficients involved in the relaxation of the star chains, we propose an equation predicting these time-shift factors. This allows us to develop an analytical equation combining all relaxation zones, which is verified by comparison with simulation results. © 2014 American Chemical Society.

Standards, Options et Recommandations pour la radiotherapie des patientes atteintes de cancer de l'endometre. Contexte. - La Federation nationale des centres de lutte contre le cancer (FNCLCC) et les Centres regionaux de lutte contre le cancer (CRLCC), en collaboration avec des partenaires des secteurs public (CHU, CHG), prive et certaines societes savantes ont entrepris depuis 1993 d'elaborer des recommandations pour la pratique clinique en cancerologie: les « Standards, Options et Recommandations » (SOR). L'objectif de l'operation SOR est d'ameliorer la qualite et l'efficience des soins aux patients atteints de cancer en fournissant aux praticiens une aide a la decision facilement utilisable. La methodologie d'elaboration des SOR repose sur une revue et une analyse critique des donnees de la litterature scientifique par un groupe d'experts pluridisciplinaire, permettant de definir, sur la base du niveau de preuve scientifique et du jugement argumente des experts, des « Standards », des « Options » et des « Recommandations », Avant publication, les SOR sont revus par des experts independants. Objectifs. - Definir, sur la base d'une revue de la litterature et de l'accord d'experts, des Standards, Options et Recommandations pour la radiotherapie des patientes atteintes de cancer. Methodes. - Un groupe de travail multidisciplinaire mis en place par la Federation nationale des centres de lutte contre le cancer (FNCLCC) a revu les donnees scientifiques disponibles concernant la radiotherapie du cancer de l'endometre. Apres selection des articles, synthese des resultats et redaction des SOR, le document a ete soumis pour relecture et approbation a des relecteurs independants et aux 20 comites techniques et medicaux des CRLCC. Resultats. - Les principales recommandations sont 1) pour les tumeurs de stade IA la surveillance est le traitement complementaire standard. Pour les tumeurs de stade IB (grade 1 ou 2), une curietherapie vaginale ou une surveillance sans traitement complementaire peuvent etre envisagees. Pour les tumeurs de stade IB (grade 3), et de stade IC, deux trailements complementaires sont possibles: une radiotherapie externe pelvienne avec une curietherapie de surimpression ou une curietherapie vaginale. 2) Le traitement des stades II peut etre preoperatoire lorsque l'atteinte du col est prouvee par un curetage ou une biopsie de l'endocol positifs. Pour les tumeurs de stade IIA apres chirurgie premiere, une curietherapie vaginale est realisee si la penetration du myometre est < 50 % ou si la tumeur est de grade 1 ou 2. En cas de penetration plus profonde ou de grade plus eleve, et pour les stades IIB, une radiotherapie externe avec curietherapie vaginale de surimpression systematique doit etre realisee. 3) Le traitement complementaire des stades IIA apres chirurgie est une radiotherapie externe soit pelvienne, soit abdominopelvienne. Dans certains cas, le traitement medical peut-etre une option. Pour les tumeurs de stade IIIB, une radiotherapie externe postoperatoire avec curietherapie doit etre realisee. Pour les tumeurs de stade IIIC, le traitement standard est une radiotherapie externe (pelvienne ou pelvienne et lomboaortique) avec eventuellement une curietherapie de surimpression (standard). En cas d'atteinte des sites extra-uterins, une irradiation abdomino-pelvienne est recommandee. 4) Les patientes inoperables doivent etre traitees par radiotherapie externe et curietherapie pour les tumeurs de stade I et II. Pour les malades inoperables du fait de leur tumeur, le traitement est le plus souvent symptomatique, associant irradiation externe et traitement medical.

Non-small cell lung carcinomas (NSCLCs) are typically resistant against apoptosis induced by standard chemotherapy. We evaluated the effects of the two potential antitumor agents of the lamellarin class on a highly apoptosis-resistant NSCLC cell line. Both the marine alkaloid lamellarin-D and its synthetic amino derivative PM031379 induced the activation of Bax, the mitochondrial release of cytochrome c and apoptosis-inducing factor (AIF), as well as the activation of caspase-3. However, only PM031379 triggered cell death and sign of nuclear apoptosis coupled to the nuclear translocation of AIF. Depletion of AIF with small interfering RNA or microinjection of a neutralizing anti-AIF antibody largely prevented PM031379-induced cytotoxicity, underscoring the essential contribution of AIF to NSCLC killing. Using NSCLC cells lacking mitochondrial DNA, we showed that the generation of mitochondrial reactive oxygen species (ROS) was crucial for the PM031379-induced translocation of AIF to the nucleus and subsequently cell death. Pretreatment of NSCLC cells with menadione, a mitochondrial ROS generator, was able to restore the deficient chemotherapy-induced apoptosis of NSCLC cells. Altogether, these data suggest that mitochondrial ROS generation is crucial for overriding the chemoresistance of NSCLC cells. Moreover, this study delineates the unique mechanism of action of lamellarins as potential anticancer agents.

Bended' 1, 3 or 'linear' 2 pyrrolidino-fused (aza)carbazoles were prepared and screened towards a few cancer-related targets. Whereas 'bended' derivatives 1 and 3 proved to be weakly toxic, several members of the 'linear' family strongly interact with DNA, especially derivative 28a.

Allogeneic hematopoietic stem cell transplantation is often used to treat hematologic malignancies. The efficacy of this procedure is due to both myeloablative conditioning and graft-versus-leukemia (GVL). However, the disadvantages of allogeneic transplantation include graft-versus-host disease (GVHD), relapse from the original tumor, and patient susceptibility to opportunistic infections. Lately, allogeneic transplantation has been developed to treat solid tumors, with the expectation that graft-versus-tumor (GVT), like GVL, will have a significant anti-tumor effect. This effect has been demonstrated in renal carcinomas, and with less evidence in breast cancers. Five patients with malignant ovarian tumors resistant to chemotherapy underwent allogeneic transplantation, four from bone marrow, and one from peripheral blood stem cells. All donors were HLA-identical siblings. One patient received a myeloablative conditioning regimen, while the other four received a non-myeloablative regimen. Two patients received donor lymphocyte infusions (DLI). Four of the patients presented with acute or chronic GVHD associated with tumor regression of at least 50%. These tumor regressions were measured by CA-125 levels and CT scans. The fifth patient died of rapid progression just after transplantation. Of the four transplantation survivors, three received a non-myeloablative regimen which did not seem to reduce treatment effectiveness. While it did reduce toxicity, one of these patients died of GVHD after 127 days. DLI was administered to two patients. These infusions seemed to promote GVHD which was able to control disease progression for one patient and had no apparent effect on the other. Allograft of hematopoietic stem cells might be of interest in ovarian cancer. The results in one patient also suggest that DLI may be an effective immunotherapy, although doses and timing need to be determined. The number of cases presented is small, however, and clinical experience on a larger scale will be required to determine the real clinical efficacy of graft versus cancerous ovarian cells.

1Centre Leon Berard, Lyon; 2FNCLCC, Paris; 3Institut Bergonie, Bordeaux; 4Centre Jean Perrin, Clermont-Ferrand; 5Centre Paul Papin, Angers; 6CHU Bretonneau, Tours; 7Centre Alexis Vautrin, Nancy; 8Centre Henri Becquerel, Rouen; 9CHU, Angers; 10CHU, Hopital Arnaud de Villeneuve, Montpellier; 11Centre Paul Strauss, Strasbourg; 12Clinique Sainte-Catherine, Avignon, France British Journal of Cancer (2001) 84(Supplement 2), 31–36 © 2001 FNCLCC doi: 10.1054/ bjoc.2001.1760, available online at http://www.idealibrary.com on

Specific phosphorylation of serine- and arginine-rich pre-mRNA splicing factors (SR proteins) is one of the key determinants regulating splicing events. Several kinases involved in SR protein phosphorylation have been identified and characterized, among which human DNA topoisomerase I is known to have DNA-relaxing activity. In this study, we have investigated the mechanism of splicing inhibition by a glycosylated indolocarbazole derivative (NB-506), a potent inhibitor of both kinase and relaxing activities of topoisomerase I. NB-506 completely inhibits the capacity of topoisomerase I to phosphorylate, in vitro, the human splicing factor 2/alternative splicing factor (SF2/ASF). This inhibition is specific, because NB-506 does not demonstrate activity against other kinases known to phosphorylate SF2/ASF such as SR protein kinase 1 and cdc2 kinase. Importantly, HeLa nuclear extracts competent in splicing but not splicing-deficient cytoplasmic S100 extracts treated with the drug fail to phosphorylate SF2/ASF and to support splicing of pre-mRNA substrates containing SF2/ASF-target sequences. Native gel analysis of splicing complexes revealed that the drug affects the formation of the spliceosome, a dynamic ribonucleoprotein structure where splicing takes place. In the presence of the drug, neither pre-spliceosome nor spliceosome is formed, demonstrating that splicing inhibition occurs at early steps of spliceosome assembly. Splicing inhibition can be relieved by adding phosphorylated SF2/ASF, showing that extracts treated with NB-506 lack a phosphorylating activity required for splicing. Moreover, NB-506 has a cytotoxic effect on murine P388 leukemia cells but not on P388CPT5 camptothecin-resistant cells that carry two point mutations in conserved regions of topoisomerase I gene (Gly361Val and Asp709Tyr). After drug treatment, P388 cells accumulated hypophosphorylated forms of SR proteins and polyadenylated RNA in the nucleus. In contrast, neither SR protein phosphorylation nor polyadenylated mRNA distribution was affected in P388 CPT5-treated cells. Consistently, NB506 treatment altered the mRNA levels and/or splicing pattern of several tested genes (Bcl-X, CD 44, SC35, and Sty) in P388 cells but not in P388 CPT5 cells. The study shows for the first time that indolocarbazole drugs targeting topoisomerase I can affect gene expression by modulating pre-mRNA splicing through inhibition of SR proteins phosphorylation.

AIDS in Africa is characterized by the equal distribution of mortality between the two genders because of highly virulent human immunodeficiency virus type 1 (HIV-1) strains. The viral protein Tat trans-activates viral gene expression and is essential for HIV-1 replication. We chemically synthesized six different Tat proteins, with sizes ranging from 86 to 101 residues, from HIV-1 isolates located in different parts of the world including highly virulent African strains. Protein purification, mass spectroscopy, and amino acid analysis showed that the synthesis was successful in each case but with different yields. We show that all have the ability to bind the HIV long terminal repeat (LTR) RNA trans-activation response element (TAR) region, involved in Tat-mediated trans-activation, but structural heterogeneities are revealed by circular dichroism. These Tat synthetic proteins cross membranes but differ in their ability to trans-activate an HIV LTR-reporter gene in stably transfected HeLa cells. Two Tat proteins from virulent African HIV-1 strains were much more active than those from Europe and the United States. The interferon-induced kinase (PKR), involved in cell antiviral defense, phosphorylates only Tat variants corresponding to less or nonvirulent HIV-1 isolates. Our results indicate that the high virulence of some African HIV-1 strains could be related to Tat activity.

International audience

Il est indispensable d'acquérir certaines informations sur l'épidémiologie d'un foyer de maladie du sommeil, pour définir une stratégie de lutte bien adaptée et efficace. Le cas du foyer centrafricain de Nola-Bilolo, en pleine reviviscence, montre l'intérêt d'une enquête auprès des malades pour la recherche des lieux de contamination probables. Cette enquête, réalisée auprès de 142 malades, a permis d'acquérir des connaissances plus fiables que celles obtenues lors d'une campagne de dépistage actif ou par le simple relevé des fiches médicales des malades dépistés passivement. Elle a permis de cerner les principaux lieux et moments du contact homme/tsé-tsé dans le cas de ce foyer forestier et de souligner la grande mobilité des malades en saison sèche. Ainsi a-t-il été possible de mieux cibler les endroits particulièrement adaptés à la lutte antivectorielle par piégeage et donc d'optimiser le rapport efficacité/coût de cette lutte. (Résumé d'auteur)

The synthesis of two peptidic derivatives, including an anilinoacridine chromophore (related to the antileukemic drug amsacrine) and either the tetrapeptide SPKK (a nucleic acid-binding unit) (1) or the octapeptide SPKKSPKK (2), has been carried out. The interaction of both drugs with DNA has been studied. Binding data are consistent with a model in which the acridine nucleus occupies an intercalation site and the tetrapeptidic or octapeptidic portion is located in the DNA minor groove. Compound 1 fully intercalates into DNA. In contrast, minor groove binding of the octapeptide SPKKSPKK seems to partially modify the intercalative properties of the acridine moiety of 2. In vitro cytostatic and cytotoxic activities against a murine leukemia cell line (L1210), as well as inhibition of [3H]thymidine incorporation, are reported. Compound 1, which is a better inhibitor of DNA synthesis than 2, is also 2.8-fold more potent in terms of growth inhibition. Both drugs are efficient cytostatic agents, but are weakly cytotoxic. The DNA-binding abilities of the two molecules are well correlated to their biological properties. Thus, DNA can be considered as the primary target for these new ligands.

A study on catchment areas was carried out at Antanimora (Prefecture of Fort Dauphin, southern Madagascar) , in 1967, for studying the effects of anti-erosion works on water savings in arid zone. Two adjoining catchment areas were defined : Taimandaha’s (155 ha) and lanamolera's (185 ha), the latter having been used as a sample area. Low stone walls, 0,50 high and with aim vertical spacing, were built on the Taimandaha area. A five years continuous operation showed the protective ivorks efficiency, namely : — cutting down of flood picks ; — better use of water on the treated area due to decreased run-off ; — increase of small flows during the dry period, and — important decrease of the earth and fertilizing elements losses., Une étude sur bassins versants a été réalisée entre 1962 et 1967 à Antanimora, dans le Sud de Madagascar (Préfecture de Fort-Dauphin), pour tester l’influence des travaux antiérosifs sur l’économie de l’eau en zone aride. Deux bassins versants voisins : Tsimandaha (155 ha) et Ianamolora (185 ha) ont été délimités, le second étant destiné à servir de témoin. Sur le bassin de Tsimandaha, on a construit, le long des courbes de niveau, des murettes en pierre sèche de 0,50 m de hauteur, séparées l’une de l’autre par une distance verticale de 4 m. Cinq années d’expérimentation continue ont montré l’efficacité des travaux de protection, à savoir : — écrêtement des pointes de crues ; — meilleure utilisation de l’eau sur le bassin traité par suite de la diminution du ruissellement ; — augmentation des petits débits de saison sèche ; — diminution importante des pertes en terre et en éléments fertilisants., Goujon P., Bailly C. Rapport III.11. Aménagements antiérosifs et économie de l’eau. In: Influence des activités de l'homme sur le cycle hydrométéorologique. Compte rendu des treizièmes journées de l'hydraulique. Paris, 16-18 septembre 1974. Tome 1, 1975.

International audience; Wall pressure fluctuations beneath a turbulent boundary layer in the presence of a mean pressure gradient are investigated in this study. The mean pressure gradient is achieved by changing the ceiling angle of a rectangular channel designed for flow-acoustic measurements. Wall pressure spectra are measured for zero-, adverse-and favorable-pressure-gradient boundary layers by using a pin-hole microphone in conjunction with a high-frequency-calibration procedure. A direct measurement of the wall pressure wavenumber-frequency spectrum Φ pp (k 1 , k 2 , ω) is also performed with the use of a rotating linear antenna of remote microphones. The microphone array has been optimized to improve its response with respect to previous works (Arguillat et al., 2010). Both aerodynamic and acoustic components of the wavenumber-frequency spectrum can thus be identified and are investigated.

A sandwich panel based on a multiscale architectured material is developed for structural and EM absorption performances. At the nanoscale level, carbon nanotubes are dispersed in a polymer to obtain a conductive material. This composite is then foamed into a micro porous solid to improve EM absorption and to decrease the density. The foam is inserted in a millimeter scale hexagonal metallic honeycomb lattice. The combination of the metallic honeycomb and the polymeric foam provides high bending, impact and crushing performances and a moderate thermal conductivity. This hybrid is used as core for sandwich panels, produced by the addition of two EM transparent face-sheets made of glass fiber reinforced polymers. EM absorption around 90% is achieved in the 10-40 GHz frequency band with a 8.8 mm thick sandwich panel.

The topoisomerase I poison CPT-11 has proved efficient for the treatment of untreated metastatic colorectal cancers (CRC) and those refractory to fluoropyrimidines. However, the interpatient variability is important. A previous in vitro study suggested that measurements of the level of topoisomerase I-DNA intermediates trapped by camptothecin may be useful to estimate the chemosensitivity of colon carcinoma cell lines. To verify this hypothesis, we developed an immuno-assay to detect covalent topoisomerase I-DNA complexes in a series of human colorectal cancers xenografted in nude mice. Six human CRCs were selected for their distinctive p53 and microsatellite instability (MSI) status. Tumour lysates, prepared from mice untreated or treated with CPT-11, were fractionated onto CsCl gradients to separate free and DNA-bound topoisomerase I by centrifugation. Interestingly, significant levels of DNA-topoisomerase I complexes were detected in the tumours most responsive to the treatment with CPT-11, irrespective of their MSI and p53 phenotypes. Our in vivo study fully agrees with the predictions from the in vitro data indicating that evaluation of topoisomerase I-DNA complexes would be useful to predict the response of CRC to a treatment with CPT-11.