473 research outputs found

    A Framework for n-dimension Visibility Calculation

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    4 pagesVisibility computation is a fundamental task in computer graphics, as in many other scientific domains. While it is well understood in two dimensions, this does not remain true in high dimensional spaces. Using Grassmann Algebra, we propose a framework for solving visibility problems in any n-dimensional spaces, for n ≥ 2. Our presentation recalls the problem statement, in two and three dimensions. Then, we formalize the space of n-dimensional lines. Finally, we show how this leads to a global framework for visibility computations, giving an example of use with exact soft shadows

    Wild-type and central DNA flap defective HIV-1 lentiviral vector genomes: intracellular visualization at ultrastructural resolution levels

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    HIV-1 and other lentiviruses have the unique ability among retroviruses to efficiently replicate in non-dividing cells as a result of the active nuclear import of their DNA genome across an interphasic nuclear membrane. Previous work has shown that a three-stranded DNA structure synthesized during HIV-1 reverse transcription, called the central DNA flap, acts as a cis-determinant of HIV-1 genome nuclear import. Concordantly, DNA Flap re-insertion in lentiviral-derived gene therapy vectors stimulates gene transfer efficiencies and complements the level of nuclear import to wild-type levels quantitatively indistinguishable from wild-type virus in all cell types and tissues examined so far. In order to define the precise nature of the replicative defect of DNA flap mutant viruses, we carried out in situ DNA hybridization experiments with electron microscopy to determine the subcellular localization of DNA flap mutant and wild-type HIV-1 genomes. We found that Flap defective DNA genomes accumulate at the cytoplasmic face of the nuclear membrane with no overlap across the nuclear membrane, whereas wild-type genomes localize throughout the nuclear compartment. These data provide an unequivocal confirmation of the role of the DNA flap in HIV-1 nuclear import and further establish that the DNA flap controls a step that immediately precedes translocation through the nuclear pore. Further, the widespread distribution of wild-type genomes within the open chromatin confirms the recent genome-wide mapping of HIV-1 cDNA integration sites and points to an as-yet poorly understood step of intranuclear transport of HIV-1 pre-integration complexes

    Attitudes et croyances envers les rêves : une approche multidimensionnelle

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    L'accord des co-auteurs est inclus dans le mémoireL’objectif était de développer un questionnaire (IDEA) afin de capter les attitudes envers les rêves et d’évaluer leurs relations avec des variables externes ainsi que le rôle qu’elles représentent dans la vie des gens. 725 participants ont complété l’IDEA et parmi ceux-ci 357 ont aussi complété des questionnaires concernant le rêve, la personnalité et le bien-être ainsi qu’un journal de rêve. Dans le premier article, une analyse factorielle de l’IDEA a dégagé 7 dimensions d’intérêt. Les individus ont été classifiés selon trois profils distincts de rêveur montrant des relations différentielles aux mesures de personnalité et de bien-être. Dans le second article, les résultats ont montré que les individus qui rapportent beaucoup de rêves, une détresse psychologique, des frontières fluides ou une capacité d’absorption croient que leurs rêves possèdent un sens. L’IDEA est un instrument utile pour la recherche et montrent que les croyances oniriques ont un rôle psychologique important.Our goals were to develop a questionnaire (the IDEA) to assess dream-related beliefs, to investigate the relations between these beliefs and waking-state variables as well as the roles they may play in peoples’ lives. In the first article, 725 participants completed the IDEA and 357 participants also completed a dream log and questionnaires on dreams, personality, and well-being. A factor analysis of the IDEA revealed 7 dimensions. Using these dimensions, individuals were classified into three distinct profiles which showed differential relations to measures of personality and well-being. In the second article, people with high dream recall, psychological distress, thin boundaries and an elevated capacity for absorption, were found to be the most likely to believe that their dream experiences are meaningful. The findings indicate that the IDEA is a useful instrument for researchers and those dream-related beliefs can play important psychological roles in people’s lives

    ISsaga is an ensemble of web-based methods for high throughput identification and semi-automatic annotation of insertion sequences in prokaryotic genomes

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    Insertion sequences (ISs) play a key role in prokaryotic genome evolution but are seldom well annotated. We describe a web application pipeline, ISsaga (http://issaga.biotoul.fr/ISsaga/issaga_index.php), that provides computational tools and methods for high-quality IS annotation. It uses established ISfinder annotation standards and permits rapid processing of single or multiple prokaryote genomes. ISsaga provides general prediction and annotation tools, information on genome context of individual ISs and a graphical overview of IS distribution around the genome of interest

    Residual HIV-1 DNA Flap-independent nuclear import of cPPT/CTS double mutant viruses does not support spreading infection

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    <p>Abstract</p> <p>Background</p> <p>The human immunodeficiency virus type 1 (HIV-1) central DNA Flap is generated during reverse transcription as a result of (+) strand initiation at the central polypurine tract (cPPT) and termination after a <it>ca</it>. 100 bp strand displacement at the central termination sequence (CTS). The central DNA Flap is a determinant of HIV-1 nuclear import, however, neither cPPT nor CTS mutations entirely abolish nuclear import and infection. Therefore, to determine whether or not the DNA Flap is essential for HIV-1 nuclear import, we generated double mutant (DM) viruses, combining cPPT and CTS mutations to abolish DNA Flap formation.</p> <p>Results</p> <p>The combination of cPPT and CTS mutations reduced the proportion of viruses forming the central DNA Flap at the end of reverse transcription and further decreased virus infectivity in one-cycle titration assays. The most affected DM viruses were unable to establish a spreading infection in the highly permissive MT4 cell line, nor in human primary peripheral blood mononuclear cells (PBMCs), indicating that the DNA Flap is required for virus replication. Surprisingly, we found that DM viruses still maintained residual nuclear import levels, amounting to 5-15% of wild-type virus, as assessed by viral DNA circle quantification. Alu-PCR quantification of integrated viral genome also indicated 5-10% residual integration levels compared to wild-type virus.</p> <p>Conclusion</p> <p>This work establishes that the central DNA Flap is required for HIV-1 spreading infection but points to a residual DNA Flap independent nuclear import, whose functional significance remains unclear since it is not sufficient to support viral replication.</p

    Exploring Smartphone Application Usage Logs with Declared Sociological Information

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    International audienceIn this paper we present an exploratory smartphone usage study with logs collected from users in the wild, combined with the sociodemographic, technological and cultural information provided by them. We observe a high diversity among users' most used applications, but by classifying applications into services we find significant correlations between service usage and socio-demographic profile. We discuss that sociological information has rich potential in characterizing smartphone usage and can be applied to interesting incentive strategies and use cases based on users' sociological context

    A highly efficient, stable, and rapid approach for ex vivo human liver gene therapy via a FLAP lentiviral vector

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    Allogenic hepatocyte transplantation or autologous transplantation of genetically modified hepatocytes has been used successfully to correct congenital or acquired liver diseases and can be considered as an alternative to orthotopic liver transplantation. However, hepatocytes are neither easily maintained in culture nor efficiently genetically modified and are very sensitive to dissociation before their reimplantation into the recipient. These difficulties have greatly limited the use of an ex vivo approach in clinical trials. In the present study, we have shown that primary human and rat hepatocytes can be efficiently transduced with a FLAP lentiviral vector without the need for plating and culture. Efficient transduction of nonadherent primary hepatocytes was achieved with a short period of contact with vector particles, without modifying hepatocyte viability, and using reduced amounts of vector. We also showed that the presence of the DNA FLAP in the vector construct was essential to reach high levels of transduction. Moreover, transplanted into uPA/SCID mouse liver, lentivirally transduced primary human hepatocytes extensively repopulated their liver and maintained a differentiated and functional phenotype as assessed by the stable detection of human albumin and antitrypsin in the serum of the animals for months. In conclusion, the use of FLAP lentiviral vectors allows, in a short period of time, a high transduction efficiency of human functional and reimplantable hepatocytes. This work therefore opens new perspectives for the development of human clinical trials based on liver-directed ex vivo gene therapy.info:eu-repo/semantics/publishedVersio

    Advances in nanocarriers as drug delivery systems in Chagas disease

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    Chagas disease is one of the most important public health problems in Latin America due to its high mortality and morbidity levels. There is no effective treatment for this disease since drugs are usually toxic with low bioavailability. Serious efforts to achieve disease control and eventual eradication have been unsuccessful to date, emphasizing the need for rapid diagnosis, drug development, and a reliable vaccine. Novel systems for drug and vaccine administration based on nanocarriers represent a promising avenue for Chagas disease treatment. Nanoparticulate systems can reduce toxicity, and increase the efficacy and bioavailability of active compounds by prolonging release, and therefore improve the therapeutic index. Moreover, nanoparticles are able to interact with the host’s immune system, modulating the immune response to favour the elimination of pathogenic microorganisms. In addition, new advances in diagnostic assays, such as nanobiosensors, are beneficial in that they enable precise identification of the pathogen. In this review, we provide an overview of the strategies and nanocarrier-based delivery systems for antichagasic agents, such as liposomes, micelles, nanoemulsions, polymeric and non-polymeric nanoparticles. We address recent progress, with a particular focus on the advances of nanovaccines and nanodiagnostics, exploring new perspectives on Chagas disease treatment
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