Châtenay-Malabry, France
Châtenay-Malabry, France

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Mayola E.,University Paris - Sud | Mayola E.,UniverSud Paris | Gallerne C.,University Paris - Sud | Esposti D.D.,University Paris - Sud | And 15 more authors.
Apoptosis | Year: 2011

A high resistance and heterogeneous response to conventional anti-cancer chemotherapies characterize malignant cutaneous melanoma, the most aggressive and deadly form of skin cancer. Withaferin A (WFA), a withanolide derived from the medicinal plant Withania somnifera, has been reported for its anti-tumorigenic activity against various cancer cells. For the first time, we examined the death-inducing potential of WFA against a panel of four different human melanoma cells and investigated the cellular mechanisms involved. WFA induces apoptotic cell death with various IC50 ranging from 1.8 to 6.1 lM. The susceptibility of cells toward WFA-induced apoptosis correlated with low Bcl-2/Bax and Bcl-2/Bim ratios. In all cell lines, the apoptotic process triggered by WFA involves the mitochondrial pathway and was associated with Bcl-2 down regulation, Bax mitochondrial translocation, cytochrome c release into the cytosol, transmembrane potential (DWm) dissipation, caspase 9 and caspase 3 activation and DNA fragmentation. WFA cytotoxicity requires early reactive oxygen species (ROS) production and glutathione depletion, the inhibition of ROS increase by the antioxidant N-acetylcysteine resulting in complete suppression of mitochondrial and nuclear events. Altogether, these results support the therapeutic potential of WFA against human melanoma. © Springer Science+Business Media, LLC 2011.


Indran I.R.,National University of Singapore | Tufo G.,University Paris - Sud | Tufo G.,French Institute of Health and Medical Research | Tufo G.,UniverSud Paris | And 4 more authors.
Biochimica et Biophysica Acta - Bioenergetics | Year: 2011

Defective or inefficient apoptosis is an acquired hallmark of cancer cells. Thus, a thorough understanding of apoptotic signaling pathways and insights into apoptosis resistance mechanisms are imperative to unravel novel drug targets for the design of more effective and target selective therapeutic strategies. This review aims at providing an overview of the recent understanding of apoptotic signaling pathways, the main mechanisms by which cancer cells resist apoptotic insults, and discusses some recent attempts to target the mitochondrion for restoring efficient cell death signaling in cancer cells. This article is part of a Special Issue entitled: Bioenergetics of Cancer. © 2011 Published by Elsevier B.V.


Brenner C.,University Paris - Sud | Brenner C.,UniverSud Paris | Subramaniam K.,National University of Singapore | Pertuiset C.,University Paris - Sud | And 2 more authors.
Oncogene | Year: 2011

Mitochondria have important functions in mammalian cells as the energy powerhouse and integrators of the mitochondrial pathway of apoptosis. The adenine nucleotide translocase (ANT) is a family of proteins involved in cell death pathways that perform distinctly opposite functions to regulate cell fate decisions. On the one hand, ANT catalyzes the adenosine triphosphate export from the mitochondrial matrix to the intermembrane space with the concomitant import of ADP from the intermembrane space to the matrix. On the other hand, during periods of stress, ANT could function as a lethal pore and trigger the process of mitochondrial membrane permeabilization, which leads irreversibly to cell death. In human, ANT is encoded by four homologous genes, whose expression is not only tissue specific, but also varies according to the pathophysiological state of the cell. Recent evidence revealed a differential role of the ANT isoforms in apoptosis and a deregulation of their expression in cancer. In this review, we introduce the current knowledge of ANT in apoptosis and cancer cells and propose a novel classification of ANT isoforms. © 2011 Macmillan Publishers Limited All rights reserved.


Peralta C.,Institute dInvestigacions Biomediques August Pi i Sunyer | Peralta C.,Research Center Biomedica En Red Of Enfermedades Hepaticas gestivas | Brenner C.,University Paris - Sud | Brenner C.,UniverSud Paris
Current Medicinal Chemistry | Year: 2011

In many physiopathological conditions, the cell controls its proper dysfunction via activation of the unfolded protein response to restore efficient protein synthesis and folding in the endoplasmic reticulum. However, whether the aim of unfolded protein response is to promote the cell survival, it can also lead to induction of cell death and then affect the cell fate. Recently, endoplasmic reticulum stress appeared to be critical for acute as well as chronic diseases including neurodegeneration, cardiac disease, cancer, obesity, type 2 diabetes, and ischemia/reperfusion injury. Therefore, inhibition of the endoplasmic reticulum stress could constitute a promising therapeutic strategy to limit cellular damage in pathologies such as hepatic ischemia/reperfusion. © 2011 Bentham Science Publishers Ltd.


Gaussens B.,UniverSud Paris | Gaussens B.,Leroy Somer | Hoang E.,UniverSud Paris | Saint-Michel J.,Leroy Somer | And 3 more authors.
IEEE Transactions on Magnetics | Year: 2014

An innovative approach, named topology exploration, is introduced in this paper. The aim of this approach is to help in the creation of electromagnetic devices, and to explore a priori unknown structures. In so doing, a general analytical solution of the magnetic field in static-excited cylindrical machines is developed, and then coupled to a stochastic procedure to determine if some structures are viable. The analytical model can account for variable boundary conditions, and hence, is suitable to determine electromagnetic performances of any structures. After 3 months of calculations, the topology exploration approach revealed interesting results showing the validity of the method. © 1965-2012 IEEE.


Adelaide L.,University Paris Est Creteil | Richard B.,University Paris Est Creteil | Richard B.,UniverSud Paris | Ragueneau F.,UniverSud Paris | Cremona C.,Direction de la Recherche et de LInnovation
European Journal of Environmental and Civil Engineering | Year: 2012

One of major causes responsible for the performance loss of reinforced concrete structures is the corrosion phenomenon. Thereby, taking into account the local effects of the steel/concrete interface is of primary importance to predict properly the response of corroded reinforced concrete structures. A multifiber-based model including the steel/concrete interface is proposed. This interface model allows taking into consideration the bond strength variation due to corrosion. Such an approach leads to reasonable computational costs which a powerful feature of the model. A numerical study of beams already studied in the French project « benchmark des poutres de la Rance» is proposed in order to show the efficiency and reliability of the proposed model. © 2012 Taylor & Francis.


Roche D.B.,Institute Of Genomique | Roche D.B.,French National Center for Scientific Research | Roche D.B.,University of Évry Val d'Essonne | Roche D.B.,UniverSud Paris | And 3 more authors.
Protein Science | Year: 2015

As the largest fraction of any proteome does not carry out enzymatic functions, and in order to leverage 3D structural data for the annotation of increasingly higher volumes of sequence data, we wanted to assess the strength of the link between coarse grained structural data (i.e., homologous superfamily level) and the enzymatic versus non-enzymatic nature of protein sequences. To probe this relationship, we took advantage of 41 phylogenetically diverse (encompassing 11 distinct phyla) genomes recently sequenced within the GEBA initiative, for which we integrated structural information, as defined by CATH, with enzyme level information, as defined by Enzyme Commission (EC) numbers. This analysis revealed that only a very small fraction (about 1%) of domain sequences occurring in the analyzed genomes was found to be associated with homologous superfamilies strongly indicative of enzymatic function. Resorting to less stringent criteria to define enzyme versus non-enzyme biased structural classes or excluding highly prevalent folds from the analysis had only modest effect on this proportion. Thus, the low genomic coverage by structurally anchored protein domains strongly associated to catalytic activities indicates that, on its own, the power of coarse grained structural information to infer the general property of being an enzyme is rather limited. © 2015 The Protein Society.


Dionisi D.,UniverSud Paris | Dionisi D.,CNR Institute of atmospheric Sciences and Climate | Keckhut P.,UniverSud Paris | Liberti G.L.,CNR Institute of atmospheric Sciences and Climate | And 2 more authors.
Atmospheric Chemistry and Physics | Year: 2013

A methodology to identify and characterize cirrus clouds has been developed and applied to the multichannel-multiwavelength Rayleigh-Mie-Raman (RMR) lidar in Rome Tor Vergata (RTV). A set of 167 cirrus cases, defined on the basis of quasi-stationary temporal period conditions, has been selected in a data set consisting of about 500 h of nighttime lidar sessions acquired between February 2007 and April 2010. The derived lidar parameters (effective height, geometrical and optical thickness and mean back-scattering ratio) and the cirrus mid-height temperature (estimated from the radiosonde data of Pratica di Mare, WMO, World Meteorological Organization, site no. 16245) of this sample have been analyzed by the means of a clustering multivariate analysis. This approach identified four cirrus classes above the RTV site: two thin cirrus clusters in mid- and upper troposphere and two thick cirrus clusters in mid-upper troposphere. These results, which are very similar to those derived through the same approach at the lidar site of the Observatoire de Haute-Provence (OHP), allows characterization of cirrus clouds over the RTV site and attests to the robustness of such classification.

To acquire some indications about the cirrus generation methods for the different classes, analyses of the extinction-to-backscatter ratio (lidar ratio, LReff, in terms of frequency distribution functions and dependencies on the mid-height cirrus temperature, have been performed. A preliminary study relating some meteorological parameters (e.g., relative humidity, wind components) to cirrus clusters has also been conducted.

The RTV cirrus results, recomputed through the cirrus classification by Sassen and Cho (1992), show good agreement with other midlatitude lidar cirrus observations for the relative occurrence of subvisible (SVC), thin and opaque cirrus classes (10%, 49% and 41%, respectively). The overall mean value of cirrus optical depth is 0.37 ± 0.18, while most retrieved LReff values range between 10-60 sr, and the estimated mean value is 31 ± 15 sr, similar to LR values of lower latitude cirrus measurements.

The obtained results are consistent with previous studies conducted with different systems and confirm that cirrus classification based on a statistical approach seems to be a good tool both to validate the height-resolved cirrus fields calculated by models and to investigate the key processes governing cirrus formation and evolution. However, the lidar ratio and optical depth analyses are affected by some uncertainties (e.g., lidar error noise, multiple scattering effects, supercooled water clouds) that reduce the confidence of the results. Future studies are needed to improve the characterization of the cirrus optical properties and, thus, the determination of their radiative impact. © 2013 Author(s).f 0.


Dionisi D.,UniverSud Paris | Dionisi D.,CNR Institute of atmospheric Sciences and Climate | Keckhut P.,UniverSud Paris | Courcoux Y.,UniverSud Paris | And 9 more authors.
Atmospheric Measurement Techniques | Year: 2015

A new lidar system devoted to tropospheric and lower stratospheric water vapor measurements has been installed at the Maïdo altitude station facility of Réunion island, in the southern subtropics. To evaluate the performances and the capabilities of the new system with a particular focus on UTLS (Upper Troposphere Lower Stratosphere) measurements, the Maïdo Lidar Calibration Campaign (MALICCA) was performed in April 2013. Varying the characteristics of the transmitter and the receiver components, different system configuration scenarios were tested and possible parasite signals (fluorescent contamination, rejection) were investigated. A hybrid calibration methodology has been set up and validated to insure optimal lidar calibration stability with time. In particular, the receiver transmittance is monitored through the calibration lamp method that, at the moment, can detect transmittance variations greater than 10-15%. Calibration coefficients are then calculated through the hourly values of IWV (Integrated Water Vapor) provided by the co-located GPS. The comparison between the constants derived by GPS and Vaisala RS92 radiosondes launched at Maïdo during MALICCA, points out an acceptable agreement in terms of accuracy of the mean calibration value (with a difference of approximately 2-3%), but a significant difference in terms of variability (14% vs. 7-9%, for GPS and RS92 calibration procedures, respectively). We obtained a relatively good agreement between the lidar measurements and 15 co-located and simultaneous RS92 radiosondes. A relative difference below 10% is measured in the low and middle troposphere (2-10 km). The upper troposphere (up to 15 km) is characterized by a larger spread (approximately 20%), because of the increasing distance between the two sensors.

To measure water vapor in the UTLS region, nighttime and monthly water vapor profiles are presented and compared. The good agreement between the lidar monthly profile and the mean WVMR profile measured by satellite MLS (Microwave Limb Sounder) has been used as a quality control procedure of the lidar product, attesting the absence of significant wet biases and validating the calibration procedure. Due to its performance and location, the MAIDO H2O lidar will become a reference instrument in the southern subtropics, insuring the long-term survey of the vertical distribution of water vapor. Furthermore, this system allows the investigation of several scientific themes, such as stratosphere-troposphere exchange, tropospheric dynamics in the subtropics, and links between cirrus clouds and water vapor. © 2015 Author(s). CC Attribution 3.0 License.


Busic A.,French Institute for Research in Computer Science and Automation | Fourneau J.M.,UniverSud Paris
Proceedings - 7th International Conference on the Quantitative Evaluation of Systems, QEST 2010 | Year: 2010

We present new algorithms we have recently introduced and which provide iterative component-wise bounds of the steady-state distribution of Markov chains. At each iteration we improve the quality of the bounds and these bounds are tight as the limit is the exact solution. As the algorithms are based on the product matrix-vector and properties of (max,+) sequences, they can easily be included into numerical packages. We present some examples and how we have implemented these algorithms in the Xborne tool. © 2010 IEEE.

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