90 research outputs found

    Switching a spin-valve back and forth by current-induced domain wall motion

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    We have studied the current-induced displacement of a domain wall (DW) in the permalloy (Py) layer of a Co/Cu/Py spin valve structure at zero and very small applied field. The displacement is in opposite direction for opposite dc currents, and the current density required to move DW is only of the order of 10^6 A/cm^2. For H = 3 Oe, a back and forth DW motion between two stable positions is observed. We also discuss the effect of an applied field on the DW motion.Comment: 4 pages, 3 figure

    Uptake and transport of novel amphiphilic polyelectrolyte-insulin nanocomplexes by caco-2 cells - towards oral insulin

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    “The original publication is available at www.springerlink.com”. Copyright SpringerPurpose: The influence of polymer architecture on cellular uptake and transport across Caco-2 cells of novel amphiphilic polyelectrolyte-insulin nanocomplexes was investigated. Method: Polyallylamine (PAA) (15 kDa) was grafted with palmitoyl chains (Pa) and subsequently modified with quaternary ammonium moieties (QPa). These two amphiphilic polyelectrolytes (APs) were tagged with rhodamine and their uptake by Caco-2 cells or their polyelectrolyte complexes (PECs) with fluorescein isothiocyanate-insulin (FITC-insulin) uptake were investigated using fluorescence microscopy. The integrity of the monolayer was determined by measurement of transepithelial electrical resistance (TEER). Insulin transport through Caco-2 monolayers was determined during TEER experiments. Result: Pa and insulin were co-localised in the cell membranes while QPa complexes were found within the cytoplasm. QPa complex uptake was not affected by calcium, cytochalasin D or nocodazole. Uptake was reduced by co-incubation with sodium azide, an active transport inhibitor. Both polymers opened tight junctions reversibly where the TEER values fell by up to 35 % within 30 minutes incubation with Caco-2 cells. Insulin transport through monolayers increased when QPa was used (0.27 ngmL-1 of insulin in basal compartment) compared to Pa (0.14 ngmL-1 of insulin in basal compartment) after 2 hours. Conclusion: These APs have been shown to be taken up by Caco-2 cells and reversibly open tight cell junctions. Further work is required to optimise these formulations with a view to maximising their potential to facilitate oral delivery of insulin.Peer reviewe

    Restituting intestinal epithelial cells exhibit increased transducibility by adenoviral vectors

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    Background and aims While mature enterocytes are resistant to transduction by adenovirus type 5 (Ad5) vectors, undifferentiated cells are transduced much more efficiently. Our purpose was to study enterocyte transduction in models of intestinal wound healing. Methods Transduction was studied ex vivo using cultures of endoscopic biopsies and in vitro utilizing Caco-2 cells in models of mucosal wound healing. Vectors carried either the LacZ or the luciferase gene. CAR (coxsackievirus and adenovirus receptor) and integrins were studied with transduction inhibition and immunofluorescent staining. Results Increased transduction efficiency was observed for a subset of enterocytes with a flattened de-differentiated phenotype present at the edge of cultured biopsies. In the in vitro systems, expanding Caco-2 cell monolayers exhibited increased transducibility that was time- and dose-dependent, reaching virtually 100% in cells along the leading edge at high viral load. Bioluminescence activity of transduced expanding monolayers was up to 3-fold greater than that of non-expanding monolayers (‘fence’ system, 48 h, MOI 1000, p < 0.05). Mitomycin C pre-treatment did not affect levels of transduction in expanding monolayers. At the highest viral load tested, CAR or integrin blocking prior to virus application resulted in 39.4% and 45.4% reduction in transduction levels ( p < 0.05). Immunofluorescence revealed altered expression of CAR on the migrating edge of the Caco-2 cultures and the expression of CAR on the apical membrane of biopsy enterocytes. Conclusions Increased CAR and integrin accessibility in migrating enterocytes mediates increased transduction by Ad5 vectors. This subset of enterocytes provides a target for the delivery of genes of interest for both research and gene therapy applications. Copyright © 2006 John Wiley & Sons, Ltd.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/55907/1/981_ftp.pd

    The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

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    The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

    The antimalarial MMV688533 provides potential for single-dose cures with a high barrier to

    Get PDF
    The emergence and spread of Plasmodium falciparum resistance to first-line antimalarials creates an imperative to identify and develop potent preclinical candidates with distinct modes of action. Here, we report the identification of MMV688533, an acylguanidine that was developed following a whole-cell screen with compounds known to hit high-value targets in human cells. MMV688533 displays fast parasite clearance in vitro and is not cross-resistant with known antimalarials. In a P. falciparum NSG mouse model, MMV688533 displays a long-lasting pharmacokinetic profile and excellent safety. Selection studies reveal a low propensity for resistance, with modest loss of potency mediated by point mutations in PfACG1 and PfEHD. These proteins are implicated in intracellular trafficking, lipid utilization, and endocytosis, suggesting interference with these pathways as a potential mode of action. This preclinical candidate may offer the potential for a single low-dose cure for malaria

    Étude thĂ©orique d'interfaces pour l'Ă©pitaxie de l'aluminate de lanthane sur silicium

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    La miniaturisation des dispositifs Métal-oxyde-Semiconducteur (MOS) nécessitera pour l'industrie microélectronique de disposer à brÚve échéance d'un isolant de grille remplaçant SiO2 dont la trop faible épaisseur ne permettra plus d'assurer des performances suffisantes. La solution envisagée consiste à utiliser une couche plus épaisse d'un matériau de constante diélectrique supérieure (high-K). Afin de s'affranchir des défauts inhérents au dépÎt d'oxydes amorphes et de bénéficier des caractéristiques ide ales d'un matériau cristallin, l'objectif est de réaliser l'épitaxie de la pérovskite LaAIO3, oxyde le plus prometteur au niveau structural et électronique. Ceci n'ayant jamais été accompli sur Si, il s'est avéré nécessaire d'effectuer un travail d'ingénierie d'interface en étroite collaboration avec une équipe spécialisée en épitaxie par jets moléculaires. En utilisant la Théorie de la Fonctionnelle de Densité, notre but est de déterminer la meilleure interface au niveau de la croissance et des propriétés électroniques. Nous avons ainsi construit et étudié plusieurs interfaces directes et couches d'accroche isolantes. D'une part, nos résultats montrent que certaines d'entre elles présentent d'excellentes perspectives de croissance pour l'oxyde. Notre interface la plus favorable, Al0.5O1.25, est élaborée en oxydant un motif de paires d'Al sur la surface Si(001). D'autre part, les discontinuités de bandes que nous avons calculées entre Si et LaAIO3 sont à la fois proches des valeurs expérimentales (avec LaAIO3 amorphe), bien que dépendant de la structure atomique de l'interface, et satisfaisantes pour une utilisation dans les futurs dispositifs MOS.LILLE1-BU (590092102) / SudocSudocFranceF
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