A tunable, dual mode field-effect or single electron transistor

A dual mode device behaving either as a field-effect transistor or a single electron transistor (SET) has been fabricated using silicon-on-insulator metal oxide semiconductor technology. Depending on the back gate polarisation, an electron island is accumulated under the front gate of the device (SET regime), or a field-effect transistor is obtained by pinching off a bottom channel with a negative front gate voltage. The gradual transition between these two cases is observed. This dual function uses both vertical and horizontal tunable potential gradients in non-overlapped silicon-on-insulator channel

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16.

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2-/- mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this 'stress' keratin is regulated

Docosahexaenoic and eicosapentaenoic acids increase prion formation in neuronal cells

<p>Abstract</p> <p>Background</p> <p>The transmissible spongiform encephalopathies, otherwise known as prion diseases, occur following the conversion of the cellular prion protein (PrP^C) to an alternatively folded, disease-associated isoform (PrP^Sc). Recent studies suggest that this conversion occurs via a cholesterol-sensitive process, as cholesterol synthesis inhibitors reduced the formation of PrP^Scand delayed the clinical phase of scrapie infection. Since polyunsaturated fatty acids also reduced cellular cholesterol levels we tested their effects on PrP^Scformation in three prion-infected neuronal cell lines (ScGT1, ScN2a and SMB cells).</p> <p>Results</p> <p>We report that treatment with docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA) or the cholesterol synthesis inhibitor simvastatin reduced the amounts of free cholesterol in membrane extracts from prion-infected neuronal cells. Simvastatin reduced cholesterol production while DHA and EPA promoted the conversion of free cholesterol to cholesterol esters. Crucially, while simvastatin reduced PrP^Scformation, both DHA and EPA significantly increased the amounts of PrP^Scin these cells. Unlike simvastatin, the effects of DHA and EPA on PrP^Sccontent were not reversed by stimulation of cholesterol synthesis with mevalonate. Treatment of ScGT1 cells with DHA and EPA also increased activation of cytoplasmic phospholipase A₂and prostaglandin E₂production. Finally, treatment of neuronal cells with DHA and EPA increased the amounts of PrP^Cexpressed at the cell surface and significantly increased the half-life of biotinylated PrP^C.</p> <p>Conclusion</p> <p>We report that although treatment with DHA or EPA significantly reduced the free cholesterol content of prion-infected cells they significantly increased PrP^Scformation in three neuronal cell lines. DHA or EPA treatment of infected cells increased activation of phospholipase A₂, a key enzyme in PrP^Scformation, and altered the trafficking of PrP^C. PrP^Cexpression at the cell surface, a putative site for the PrP^Scformation, was significantly increased, and the rate at which PrP^Cwas degraded was reduced. Cholesterol depletion is seen as a potential therapeutic strategy for prion diseases. However, these results indicate that a greater understanding of the precise relationship between membrane cholesterol distribution, PrP^Ctrafficking, cell activation and PrP^Scformation is required before cholesterol manipulation can be considered as a prion therapeutic.</p

Identification of an Intracellular Site of Prion Conversion

Prion diseases are fatal, neurodegenerative disorders in humans and animals and are characterized by the accumulation of an abnormally folded isoform of the cellular prion protein (PrPC), denoted PrPSc, which represents the major component of infectious scrapie prions. Characterization of the mechanism of conversion of PrPC into PrPSc and identification of the intracellular site where it occurs are among the most important questions in prion biology. Despite numerous efforts, both of these questions remain unsolved. We have quantitatively analyzed the distribution of PrPC and PrPSc and measured PrPSc levels in different infected neuronal cell lines in which protein trafficking has been selectively impaired. Our data exclude roles for both early and late endosomes and identify the endosomal recycling compartment as the likely site of prion conversion. These findings represent a fundamental step towards understanding the cellular mechanism of prion conversion and will allow the development of new therapeutic approaches for prion diseases

Contribution of archaeological analogues to the comprehension of long term corrosion of concrete reinforcements

International audienc

Le paysage, objet média pour identifier les enjeux économiques, sociaux et environnementaux d'un territoire

Within the framework of a program on territorial anchoring of the ski resorts, in collaboration of geographer, economist, sociologist, political economist and ecologist, the place of the environment seemed power station little by little. This is why after specific studies on the impact of the stations on the management of water or the conflicts between tourism and agriculture, we decided to use the landscape like starting point of talks with local actors. We have postulated that landscape can become a resource built from a shared representation of the stakes which it makes it possible to identify. We analyzed by a score of talks carried out in Beaufortain (Savoy) in what the evocation of the landscape causes in the local actors the formulation of reflexions and questions relating to environmental dimensions, social and economic of the tourist development This territory was retained in reason of its strong identity which was forged with the course the history. In the years 1970, a collective strategy based the success of Beaufortain by giving rise to a specific development founded on tourism and a very active agriculture thanks to the label of origin controlled of their cheese. The first results of the talks carried out in manner semi-directive on 4 broad topics (lived, perceived contents of the landscape, practices and projects related to the landscape) make emerge 6 great stakes shared by the surveyed actors. These stakes constitute topics structuring in the representations of actors;. They make emerge the vulnerabilities specific to this territory from which a prospective work on its becoming can be committed. The objective of this communication will be to present the theoretical and methodological aspects of our research, for in the second time, to explore the possible ways of a reflexion concerted with the actors on the basis of stake identified in this first phase of research.Dans le cadre d'un programme sur l'ancrage territorial des stations de ski, dans lequel ont collaboré des équipes de géographe, économiste, sociologue, politologue et écologue, la place de l'environnement est peu à peu apparue comme centrale. C'est pourquoi après des études ponctuelles sur l'impact des stations sur la gestion de l'eau ou les conflits entre tourisme et agriculture, nous avons décidé d'utiliser le paysage comme point de départ d'entretiens d'acteurs locaux. Nous avons en effet postulé que le paysage peut devenir une ressource construite à partir d'une représentation partagée des enjeux qu'il permet d'identifier. Nous avons analysé par une vingtaine d'entretiens menés dans le Beaufortain (Savoie) en quoi l'évocation du paysage suscite chez les acteurs locaux la formulation de réflexions et de questions relatives aux dimensions environnementales, sociales et économiques du développement touristique Ce territoire a été retenu en raison de son identité forte qui s'est forgée au cours de l'histoire. Dans les années 1970, une stratégie collective a fondé la réussite du Beaufortain en donnant naissance à un développement spécifique fondé sur le tourisme et une agriculture très active grâce à l'appellation d'origine contrôlée de leur fromage. Les premiers résultats des entretiens menés de manière semi-directive sur 4 grands thèmes (le vécu, le contenu perçu du paysage, les pratiques et les projets liés au paysage ) font surgir 6 grands enjeux partagés par les acteurs enquêtés. Ces enjeux constituent des thèmes structurants dans les représentations d'acteurs ;. Ils font surgir les vulnérabilités propres à ce territoire à partir desquelles un travail prospectif sur son devenir peut être engagé. L'objectif de cette communication sera de présenter les aspects théoriques et méthodologiques de notre recherche, pour dans un second temps, explorer les voies possibles d'une réflexion concertée avec les acteurs sur la base des enjeux identifiés dans cette première phase de recherche

Contribution of archaeological analogues to the comprehension of long term corrosion of concrete reinforcements

The study of archaeological analogues is necessary to improve the knowledge on the long-term corrosion of low carbon steels that could be used in concrete to build the structures of nuclear waste storage facilities. The long-term corrosion system was previously described as a multi-layer pattern made of the Metal, the Dense Product Layer (constituted of goethite with magnetite and/or maghemite marblings - DPL), the Transformed Medium (TM) which is an interphase between the Dense Product Layer, and the last layer, the Binder.
As mainly constituted of goethite, a non-conductive phase, and assuming that the DPL pores are saturated with water, corrosion kinetic could be limited by oxygen diffusion in the water of the pores. Moreover, anodic and cathodic reactions should occur at the Metal/DPL interface. This last hypothesis was verified labelling oxygen precipitation sites with an oxygen isotope ($^{18}$O) and observing an increase of oxygen isotopic ratio at the M/DPL interface. Then, to validate the hypothesis of a diffusion control of corrosion kinetic, some investigations were performed on diffusion properties of oxygen in the DPL. For this purpose, the oxygen apparent diffusion coefficient was evaluated using diffusion cells made with DPL sampled on archaeological analogues. Then, thanks to Faraday law, it was possible to evaluate instantaneous corrosion rates (less than 0.1 $\mu$m/year). The compatibility of these rates with those obtained considering the quantity of $^{18}$O precipitated in corrosion products was discussed. Nevertheless, even if oxygen diffusion is probably the limiting factor on iron corrosion in the very specific case of water saturated media, the hydrometry of the DPL during the life time of the object and the influence of this hydrometry on corrosion mechanisms have to be verified.
Moreover, several questions were raised by TM formation and growth. Was this layer formed dissolving/precipitating corrosion products from the DPL? Unfortunately, thermodynamical data and results from our experimentation show that iron quantity obtained by this mean is not sufficient to explain TM thicknesses observed and, so far, TM formation mechanisms are still to be identified