3,211 research outputs found

    Incentive-compatible contracts for the sale information

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    An informed financial institution can trade on private information and also sell it to clients through a managed fund. To provide an incentive for the informed agent to trade in the interest of her client, the optimal contract requires that she be compensated as an increasing function of the profits of the fund. The optimal contract is also designed to limit the aggressiveness of the sum of the fund's trade and the proprieatary trade. This reduces information revelation and thes leads to greater overall trading profits than if the informed agent only conducted proprietary trades

    0383 : In vitro 3D model of in vitro angiogenesis using human endothelial cells and pericytes

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    Human tissue is three-dimensional, and requires convective transport of nutrients and waste through capillary networks to meet metabolic demands Angiogenesis is the formation of new blood vessels from the existing vasculature. It is a multi-step process that include: degradation of the basement membrane, proliferation and migration (sprouting) of endothelial cells (EC) into the extracellular matrix, alignment of EC into cords, branching, lumen formation, anastomosis, and formation of a new basement membrane. The literatture in 3D in vitro models using endothelial cells is wide, using various types of EC (essentially Human Umbilical Vein Endothelial Cells), but blood vessels are composed of two interacting cells types: endothelial cells form the inner of the vessel wall, and mural cells that wrap the first ones. Pericytes are the mural cells of microvessels. They serve as scaffolding, and they communicate with endothelial cells by direct physical contacts and paracrine signaling pathways. Presently, there are no three-dimensional in vitro models of 3D Matrices which contain human pericyte-coated capillaries. Therefore, we aim at including pericytes in a 3D vascular morphogenesis assay in order to create a 3D in vitro model more close to physiologic conditions. We’ll show and discuss our first analyzes and results, the goal of which is to provide new in vitro tools in order to better understand vascular biology, for later studies of endothelial cells-pericytes interactions, extracellular matrix-pericytes interactions, and eventually, further elucidate the role of pericytes in the microvasculature

    Divergent Changes in the Sensitivity of Maturing T Cells to Structurally Related Ligands Underlies Formation of a Useful T Cell Repertoire

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    AbstractCD4+CD8+ thymocyte differentiation requires TCR signaling induced by self-peptide/MHC ligands. Nevertheless, the resulting mature T cells are not activated by these self-complexes, whereas foreign ligands can be potent stimuli. Here, we show that the signaling properties of TCR change during thymocyte maturation, differentially affecting responses to related peptide/MHC molecule complexes and contributing to this discrimination. Weak agonists for CD4+CD8+ thymocytes lose potency during development, accompanied by a change in TCR-associated phosphorylation from an agonist to a partial agonist/antagonist pattern. In contrast, sensitivity to strong agonists is maintained, along with full signaling. This yields a mature T cell pool highly responsive to foreign antigen while possessing a wide margin of safety against activation by self-ligands

    Redirecting NK cells mediated tumor cell lysis by a new recombinant bifunctional protein

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    Natural killer (NK) cells are at the crossroad between innate and adaptive immunity and play a major role in cancer immunosurveillance. NK cell stimulation depends on a balance between inhibitory and activating receptors, such as the stimulatory lectin-like receptor NKG2D. To redirect NK cells against tumor cells, we designed bifunctional proteins able to specifically bind tumor cells and to induce their lysis by NK cells, after NKG2D engagement. To this aim, we used the ‘knob into hole' heterodimerization strategy, in which ‘knob' and ‘hole' variants were generated by directed mutagenesis within the CH3 domain of human IgG1 Fc fragments fused to an anti-CEA or anti-HER2 scFv or to the H60 murine ligand of NKG2D, respectively. We demonstrated the capacity of the bifunctional proteins produced to specifically coat tumor cells surface with H60 ligand. Most importantly, we demonstrated that these bifunctional proteins were able to induce an NKG2D-dependent and antibody-specific tumor cell lysis by murine NK cells. Overall, the results show the possibility to redirect NK cytotoxicity to tumor cells by a new format of recombinant bispecific antibody, opening the way of potential NK cell-based cancer immunotherapies by specific activation of the NKG2D receptor at the tumor sit

    Learning fuzzy rules to characterize objects of interest from remote sensing images

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    In this article a new method for learning concepts from examples of objects provided by experts for remote sensing images is presented. The goal of this method is to give the geographer expert a description of complex objects of interest extracted from very high resolution remote sensing images. The description of such objects needs to handle imprecision inherent to segmentation and very high resolution images. The first step of this approach is to classify objects composing all the examples. This classification allows the learning of a rule describing how the examples are composed regarding the segmentation. Finally, this rule is used to extract objects corresponding to the examples. Experiments on a remote sensing image of a urban landscape in Toulouse, France are presented to show the relevance of the method

    A complete pupillometry toolbox for real-time monitoring of locus coeruleus activity in rodents

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    The locus coeruleus (LC) is a region in the brainstem that produces noradrenaline and is involved in both normal and pathological brain function. Pupillometry, the measurement of pupil diameter, provides a powerful readout of LC activity in rodents, primates and humans. The protocol detailed here describes a miniaturized setup that can screen LC activity in rodents in real-time and can be established within 1–2 d. Using low-cost Raspberry Pi computers and cameras, the complete custom-built system costs only ~300 euros, is compatible with stereotaxic surgery frames and seamlessly integrates into complex experimental setups. Tools for pupil tracking and a user-friendly Pupillometry App allow quantification, analysis and visualization of pupil size. Pupillometry can discriminate between different, physiologically relevant firing patterns of the LC and can accurately report LC activation as measured by noradrenaline turnover. Pupillometry provides a rapid, non-invasive readout that can be used to verify accurate placement of electrodes/fibers in vivo, thus allowing decisions about the inclusion/exclusion of individual animals before experiments begin

    Strong enhancement of extremely energetic proton production in central heavy ion collisions at intermediate energy

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    The energetic proton emission has been investigated as a function of the reaction centrality for the system 58Ni + 58Ni at 30A MeV. Extremely energetic protons (EpNN > 130 MeV) were measured and their multiplicity is found to increase almost quadratically with the number of participant nucleons thus indicating the onset of a mechanism beyond one and two-body dynamics.Comment: 5 pages, 2 figures, submitted to Physical Review Letter
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