3,329 research outputs found

    Enhancing the selection of a model-based clustering with external qualitative variables

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    In cluster analysis, it can be useful to interpret the partition built from the data in the light of external categorical variables which were not directly involved to cluster the data. An approach is proposed in the model-based clustering context to select a model and a number of clusters which both fit the data well and take advantage of the potential illustrative ability of the external variables. This approach makes use of the integrated joint likelihood of the data and the partitions at hand, namely the model-based partition and the partitions associated to the external variables. It is noteworthy that each mixture model is fitted by the maximum likelihood methodology to the data, excluding the external variables which are used to select a relevant mixture model only. Numerical experiments illustrate the promising behaviour of the derived criterion

    Sélection de modèle pour la classification en présence d'une classification externe

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    International audienceEn classification non supervisée de données, il est souvent utile d'interpréter les résultats de la classification cherchée en regard d'une partition des individus connue a priori et obtenue sur d'autres informations que les données disponibles. Nous proposons une approche fondée sur le modèle de mélange de lois qui permet de sélectionner un modèle de classification et un nombre de classes de sorte à produire une classification qui, à la fois, s'ajuste bien aux données et présente une bonne liaison avec la partition a priori. Cette approche utilise la vraisemblance intégrée jointe des données et des deux classification en jeu. Il est à noter que l'obtention de la classification ne fait intervenir la partition a priori que dans la phase de sélection d'un modèle et non dans la phase de construction de la classification qui se fait de manière classique par maximum de vraisemblance. Des illustrations seront données et le fait de dissocier les étapes d'estimation et de sélection d'un modèle sera discuté

    Taking Free Flap Surgery Abroad: A Collaborative Approach to a Complex Surgical Problem.

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    Accessibility to health care, especially complex surgical care, represents one of the major health care disparities in developing countries. While surgical teams may be willing to travel to these areas to help address these needs, there are many logistical and ethical dilemmas inherent in this pursuit. We reviewed our approach to the establishment of the team-based surgical outreach program, wherein we perform head and neck free tissue transfer surgery in Haiti. We describe the challenges encountered in the delivery of surgical care as well as ethical dilemmas relevant to surgical outreach trips, highlighting an approach reliant on strong local cooperation. Despite the obstacles in place, our experience shows that free flap surgery can be successfully and ethically performed in these areas of great need

    Gold versus Palladium: A Regioselective Cycloisomerization of Aromatic Enynes

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    International audienceAromatic enynes can be transformed into arylnaphthalenes or benzofulvenes depending on the reaction conditions. Under gold(I) catalysis, exclusive or major 6-endo-dig cyclization took place leading to arylnaphthalenes. However, a catalytic system based on palladium iodide/1,3-Bis(diphenylphosphino)propane, in the presence of cesium carbonate as a base was necessary to furnish exclusively 5-exo-dig cyclization pattern, regardless to the electronic effects of the substituents. In the latter transformation, a mechanistic study (Kinetic Isotopic Effect, Density Functional Theory) involving a C-H activation is suggested for the exclusive benzofulvenes formation

    Identification of a GTP-bound Rho specific scFv molecular sensor by phage display selection

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    <p>Abstract</p> <p>Background</p> <p>The Rho GTPases A, B and C proteins, members of the Rho family whose activity is regulated by GDP/GTP cycling, function in many cellular pathways controlling proliferation and have recently been implicated in tumorigenesis. Although overexpression of Rho GTPases has been correlated with tumorigenesis, only their GTP-bound forms are able to activate the signalling pathways implicated in tumorigenesis. Thus, the focus of much recent research has been to identify biological tools capable of quantifying the level of cellular GTP-bound Rho, or determining the subcellular location of activation. However useful, these tools used to study the mechanism of Rho activation still have limitations. The aim of the present work was to employ phage display to identify a conformationally-specific single chain fragment variable (scFv) that recognizes the active, GTP-bound, form of Rho GTPases and is able to discriminate it from the inactive, GDP-bound, Rho in endogenous settings.</p> <p>Results</p> <p>After five rounds of phage selection using a constitutively activated mutant of RhoB (RhoBQ63L), three scFvs (A8, C1 and D11) were selected for subsequent analysis. Further biochemical characterization was pursued for the single clone, C1, exhibiting an scFv structure. C1 was selective for the GTP-bound form of RhoA, RhoB, as well as RhoC, and failed to recognize GTP-loaded Rac1 or Cdc42, two other members of the Rho family. To enhance its production, soluble C1 was expressed in fusion with the N-terminal domain of phage protein pIII (scFv C1-N1N2), it appeared specifically associated with GTP-loaded recombinant RhoA and RhoB via immunoprecipitation, and endogenous activated Rho in HeLa cells as determined by immunofluorescence.</p> <p>Conclusion</p> <p>We identified an antibody, C1-N1N2, specific for the GTP-bound form of RhoB from a phage library, and confirmed its specificity towards GTP-bound RhoA and RhoC, as well as RhoB. The success of C1-N1N2 in discriminating activated Rho in immunofluorescence studies implies that this new tool, in collaboration with currently used RhoA and B antibodies, has the potential to analyze Rho activation in cell function and tumor development.</p

    CO2 Injectivity in geological storages: an overview of program and results of the GeoCarbone-Injectivity Project

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    International audienceThe objective of the GeoCarbone-Injectivity project was to develop a methodology to study the complex phenomena involved in the near wellbore region during CO2 injection. This paper presents an overview of the program and results of the project, and some further necessary developments. The proposed methodology is based on experiments and simulations at the core scale, in order to understand (physical modelling and definition of constitutive laws) and quantify (calibration of simulation tools) the mechanisms involved in injectivity variations: fluid/rock interactions, transport mechanisms, geomechanical effects. These mechanisms and the associated parameters have then to be integrated in the models at the wellbore scale. The methodology has been applied for the study of a potential injection of CO2 in the Dogger geological formation of the Paris Basin, in collaboration with the other ANR GeoCarbone projects

    Melanin is an essential component for the integrity of the cell wall of Aspergillus fumigatus conidia

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    BACKGROUND: Aspergillus fumigatus is the most common agent of invasive aspergillosis, a feared complication in severely immunocompromised patients. Despite the recent commercialisation of new antifungal drugs, the prognosis for this infection remains uncertain. Thus, there is a real need to discover new targets for therapy. Particular attention has been paid to the biochemical composition and organisation of the fungal cell wall, because it mediates the host-fungus interplay. Conidia, which are responsible for infections, have melanin as one of the cell wall components. Melanin has been established as an important virulence factor, protecting the fungus against the host\u27s immune defences. We suggested that it might also have an indirect role in virulence, because it is required for correct assembly of the cell wall layers of the conidia. RESULTS: We used three A. fumigatus isolates which grew as white or brown powdery colonies, to demonstrate the role of melanin. Firstly, sequencing the genes responsible for biosynthesis of melanin (ALB1, AYG1, ARP1, ARP2, ABR1 and ABR2) showed point mutations (missense mutation, deletion or insertion) in the ALB1 gene for pigmentless isolates or in ARP2 for the brownish isolate. The isolates were then shown by scanning electron microscopy to produce numerous, typical conidial heads, except that the conidia were smooth-walled, as previously observed for laboratory mutants with mutations in the PKSP/ALB1 gene. Flow cytometry showed an increase in the fibronectin binding capacity of conidia from mutant isolates, together with a marked decrease in the binding of laminin to the conidial surface. A marked decrease in the electronegative charge of the conidia and cell surface hydrophobicity was also seen by microelectrophoresis and two-phase partitioning, respectively. Ultrastructural studies of mutant isolates detected considerable changes in the organisation of the conidial wall, with the loss of the outermost electron dense layer responsible for the ornamentations seen on the conidial surface in wild-type strains. Finally, analysis of the conidial surface of mutant isolates by atomic force microscopy demonstrated the absence of the outer cell wall rodlet layer which is composed of hydrophobins. CONCLUSION: These results suggest that, in addition to a protective role against the host\u27s immune defences, melanin is also a structural component of the conidial wall that is required for correct assembly of the cell wall layers and the expression at the conidial surface of adhesins and other virulence factors
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