803 research outputs found

    Lateral Effects in Fermion Antibunching

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    Lateral effects are analyzed in the antibunching of a beam of free non-interacting fermions. The emission of particles from a source is dynamically described in a 3D full quantum field-theoretical framework. The size of the source and the detectors, as well as the temperature of the source are taken into account and the behavior of the visibility is scrutinized as a function of these parameters.Comment: 22 pages, 4 figure

    Informativity and Asymmetry in Comparisons

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    Palm pairs and the general mass-transport principle

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    We consider a lcsc group G acting properly on a Borel space S and measurably on an underlying sigma-finite measure space. Our first main result is a transport formula connecting the Palm pairs of jointly stationary random measures on S. A key (and new) technical result is a measurable disintegration of the Haar measure on G along the orbits. The second main result is an intrinsic characterization of the Palm pairs of a G-invariant random measure. We then proceed with deriving a general version of the mass-transport principle for possibly non-transitive and non-unimodular group operations first in a deterministic and then in its full probabilistic form.Comment: 26 page

    Design of a regulated lentiviral vector for hematopoietic stem cell gene therapy of globoid cell leukodystrophy

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    Globoid cell leukodystrophy (GLD) is a demyelinating lysosomal storage disease due to the deficiency of the galactocerebrosidase (GALC) enzyme. The favorable outcome of hematopoietic stem and progenitor cell (HSPC)-based approaches in GLD and other similar diseases suggests HSPC gene therapy as a promising therapeutic option for patients. The path to clinical development of this strategy was hampered by a selective toxicity of the overexpressed GALC in the HSPC compartment. Here, we presented the optimization of a lentiviral vector (LV) in which miR-126 regulation was coupled to codon optimization of the human GALC cDNA to obtain a selective and enhanced enzymatic activity only upon transduced HSPCs differentiation. The safety of human GALC overexpression driven by this LV was extensively demonstrated in vitro and in vivo on human HSPCs from healthy donors. No perturbation in the content of proapoptotic sphingolipids, gene expression profile, and capability of engraftment and mutlilineage differentiation in chimeric mice was observed. The therapeutic potential of this LV was then assessed in a severe GLD murine model that benefited from transplantation of corrected HSPCs with longer survival and ameliorated phenotype as compared to untreated siblings. This construct has thus been selected as a candidate for clinical translatio

    Identifying the mechanisms underpinning recognition of structured sequences of action

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    © 2012 The Experimental Psychology SocietyWe present three experiments to identify the specific information sources that skilled participants use to make recognition judgements when presented with dynamic, structured stimuli. A group of less skilled participants acted as controls. In all experiments, participants were presented with filmed stimuli containing structured action sequences. In a subsequent recognition phase, participants were presented with new and previously seen stimuli and were required to make judgements as to whether or not each sequence had been presented earlier (or were edited versions of earlier sequences). In Experiment 1, skilled participants demonstrated superior sensitivity in recognition when viewing dynamic clips compared with static images and clips where the frames were presented in a nonsequential, randomized manner, implicating the importance of motion information when identifying familiar or unfamiliar sequences. In Experiment 2, we presented normal and mirror-reversed sequences in order to distort access to absolute motion information. Skilled participants demonstrated superior recognition sensitivity, but no significant differences were observed across viewing conditions, leading to the suggestion that skilled participants are more likely to extract relative rather than absolute motion when making such judgements. In Experiment 3, we manipulated relative motion information by occluding several display features for the duration of each film sequence. A significant decrement in performance was reported when centrally located features were occluded compared to those located in more peripheral positions. Findings indicate that skilled participants are particularly sensitive to relative motion information when attempting to identify familiarity in dynamic, visual displays involving interaction between numerous features

    ISML: an interface specification meta-language

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    In this paper we present an abstract metaphor model situated within a model-based user interface framework. The inclusion of metaphors in graphical user interfaces is a well established, but mostly craft-based strategy to design. A substantial body of notations and tools can be found within the model-based user interface design literature, however an explicit treatment of metaphor and its mappings to other design views has yet to be addressed. We introduce the Interface Specification Meta-Language (ISML) framework and demonstrate its use in comparing the semantic and syntactic features of an interactive system. Challenges facing this research are outlined and further work proposed

    miRNA-126 Orchestrates an Oncogenic Program in B Cell Precursor Acute Lymphoblastic Leukemia

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    MicroRNA (miRNA)-126 is a known regulator of hematopoietic stem cell quiescence. We engineered murine hematopoiesis to express miRNA-126 across all differentiation stages. Thirty percent of mice developed monoclonal B cell leukemia, which was prevented or regressed when a tetracycline-repressible miRNA-126 cassette was switched off. Regression was accompanied by upregulation of cell-cycle regulators and B cell differentiation genes, and downregulation of oncogenic signaling pathways. Expression of dominant-negative p53 delayed blast clearance upon miRNA-126 switch-off, highlighting the relevance of p53 inhibition in miRNA-126 addiction. Forced miRNA-126 expression in mouse and human progenitors reduced p53 transcriptional activity through regulation of multiple p53-related targets. miRNA-126 is highly expressed in a subset of human B-ALL, and antagonizing miRNA-126 in ALL xenograft models triggered apoptosis and reduced disease burden
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