570 research outputs found

    A non local unitary vector model in 3-D

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    We present a unified analysis of single excitation vector models in 3D. We show that there is a family of first order master actions related by duality transformations which interpolate between the different models. We use a Hamiltonian (2+1) analysis to show the equivalence of the self-dual and topologically massive models with a covariant non local model which propagates also a single massive excitation. It is shown how the non local terms appears naturally in the path integral framework.Comment: 13 pages, 1 figur

    Aminoethyl benzenesulfonyl fluoride and its hexapeptide (Ac-VFRSLK) conjugate are both in vitro inhibitors of subtilisin kexin isozyme-1

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    AbstractUsing a number of intramolecularly quenched fluorogenic (IQF) substrates encompassing the subtilisin kexin isozyme-1 (SKI-1)-mediated cleavage sites of various viral glycoproteins, it is revealed that 4-[2-Aminoethyl Benzene] SulfonylFluoride (AEBSF) can inhibit the proteolytic activity of SKI-1 mostly in a competitive manner. The measured IC50 values range from 200 to 800 nM depending on the nature of the substrate used. This is the first in vitro demonstration of a non-peptide inhibitor of SKI-1. In an effort to enhance the selectivity and potency of SKI-1 inhibition, a hexapeptidyl derivative containing SKI-1 consensus sequence, Ac-Val-Phe-Arg-Ser-Leu-Lys-AEBSF, was prepared. The peptide sequence was derived from the primary auto-activation site of prodomain of SKI-1 itself terminating at Leu-Lys138 and contains the crucial P4-basic and P2 alkyl side chain containing hydrophobic amino acids. Like AEBSF, the hexapeptidyl-AEBSF analog blocked SKI-1 cleavages of all IQF-substrates tested but with enhanced efficiency

    Plasma PCSK9 levels are significantly modified by statins and fibrates in humans

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    <p>Abstract</p> <p>Background</p> <p>Proprotein convertase subtilisin kexin-like 9 (PCSK9) is a secreted glycoprotein that is transcriptionally regulated by cholesterol status. It modulates levels of circulating low density lipoprotein cholesterol (LDLC) by negatively regulating low density lipoprotein receptor (LDLR) levels. PCSK9 variants that result in 'gain of function' have been linked to autosomal dominant hypercholesterolemia, while significant protection from coronary artery disease has been documented in individuals who carry 'loss of function' PCSK9 variants. PCSK9 circulates in human plasma, and we previously reported that plasma PCSK9 is positively correlated with total cholesterol and LDLC in men.</p> <p>Results</p> <p>Herein, we report the effects of two lipid-modulating therapies, namely statins and fibrates, on PCSK9 plasma levels in human subjects. We also document their effects on endogenous PCSK9 and LDLR expression in a human hepatocyte cell line, HepG2, using immunoprecipitation and immunoblot analyses. Changes in plasma PCSK9 following fenofibrate or gemfibrozil treatments (fibric acid derivatives) were inversely correlated with changes in LDLC levels (r = -0.558, p = 0.013). Atorvastatin administration (HMGCoA reductase inhibitor) significantly increased plasma PCSK9 (7.40%, p = 0.033) and these changes were inversely correlated with changes in LDLC levels (r = -0.393, p = 0.012). Immunoblot analyses of endogenous PCSK9 and LDLR expression by HepG2 cells in response to statins and fibrates showed that LDLR is more upregulated than PCSK9 by simvastatin (2.6× vs 1.5×, respectively at 10 ÎŒM), while fenofibrate did not induce changes in either.</p> <p>Conclusion</p> <p>These results suggest that <it>in vivo </it>(1) statins directly increase PCSK9 expression while (2) fibrates affect PCSK9 expression indirectly through its modulation of cholesterol levels and (3) that these therapies could be improved by combination with a PCSK9 inhibitor, constituting a novel hypercholesterolemic therapy, since PCSK9 was significantly upregulated by both treatments.</p

    Two-mirror Schwarzschild aplanats. Basic relations

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    It is shown that the theory of aplanatic two-mirror telescopes developed by Karl Schwarzschild in 1905 leads to the unified description both the prefocal and the postfocal systems. The class of surfaces in the ZEMAX optical program has been properly extended to ascertain the image quality in exact Schwarzschild aplanats. A comparison of Schwarzschild aplanats with approximate Ritchey-Chretien and Gregory-Maksutov aplanatic telescopes reveals a noticeable advantage of the former at fast focal ratio of the system.Comment: 19 page

    Time-resolved diffuse optical tomography for non-invasive flap viability assessment: Pre-clinical tests on rats

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    We present a new setup for time-resolved diffuse optical tomography based on multiple source-detector acquisitions analysed by means of the Mellin-Laplace transform. The proposed setup has been used to perform pre-clinical measurements on rats in order to show its suitability for non-invasive assessment of flap viability

    Trends in Metal Oxide Stability for Nanorods, Nanotubes, and Surfaces

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    The formation energies of nanostructures play an important role in determining their properties, including the catalytic activity. For the case of 15 different rutile and 8 different perovskite metal oxides, we find that the density functional theory (DFT) calculated formation energies of (2,2) nanorods, (3,3) nanotubes, and the (110) and (100) surfaces may be described semi-quantitatively by the fraction of metal--oxygen bonds broken and the bonding band centers in the bulk metal oxide

    L'Exposition municipale de Beaux-Arts. I

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    Exposition municipale des beaux-arts. Critique mitigée de "Guerrier furieux". Hodler a des qualités remarquables mais il manque de pondération. Talent inégal

    Template-free 13-protofilament microtubule–MAP assembly visualized at 8 A resolution

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    Microtubule-associated proteins (MAPs) are essential for regulating and organizing cellular microtubules (MTs). However, our mechanistic understanding of MAP function is limited by a lack of detailed structural information. Using cryo-electron microscopy and single particle algorithms, we solved the 8 Å structure of doublecortin (DCX)-stabilized MTs. Because of DCX’s unusual ability to specifically nucleate and stabilize 13-protofilament MTs, our reconstruction provides unprecedented insight into the structure of MTs with an in vivo architecture, and in the absence of a stabilizing drug. DCX specifically recognizes the corner of four tubulin dimers, a binding mode ideally suited to stabilizing both lateral and longitudinal lattice contacts. A striking consequence of this is that DCX does not bind the MT seam. DCX binding on the MT surface indirectly stabilizes conserved tubulin–tubulin lateral contacts in the MT lumen, operating independently of the nucleotide bound to tubulin. DCX’s exquisite binding selectivity uncovers important insights into regulation of cellular MTs

    Detecting wildlife in unmanned aerial systems imagery using convolutional neural networks trained with an automated feedback loop

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    Using automated processes to detect wildlife in uncontrolled outdoor imagery in the field of wildlife ecology is a challenging task. This is especially true in imagery provided by an Unmanned Aerial System (UAS), where the relative size of wildlife is small and visually similar to its background. This work presents an automated feedback loop which can be used to train convolutional neural networks with extremely unbalanced class sizes, which alleviates some of these challenges. This work utilizes UAS imagery collected by the Wildlife@Home project, which has employed citizen scientists and trained experts to go through collected UAS imagery and classify it. Classified data is used as inputs to convolutional neural networks (CNNs) which seek to automatically mark which areas of the imagery contain wildlife. The output of the CNN is then passed to a blob counter which returns a population estimate for the image. The feedback loop was developed to help train the CNNs to better differentiate between the wildlife and the visually similar background and deal with the disparate amount of wildlife training images versus background training images. Utilizing the feedback loop dramatically reduced population count error rates from previously published work, from +150% to −3.93% on citizen scientist data and +88% to +5.24% on expert data

    Continuous non-perturbative regularization of QED

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    We regularize in a continuous manner the path integral of QED by construction of a non-local version of its action by means of a regularized form of Dirac's ÎŽ\delta functions. Since the action and the measure are both invariant under the gauge group, this regularization scheme is intrinsically non-perturbative. Despite the fact that the non-local action converges formally to the local one as the cutoff goes to infinity, the regularized theory keeps trace of the non-locality through the appearance of a quadratic divergence in the transverse part of the polarization operator. This term which is uniquely defined by the choice of the cutoff functions can be removed by a redefinition of the regularized action. We notice that as for chiral fermions on the lattice, there is an obstruction to construct a continuous and non ambiguous regularization in four dimensions. With the help of the regularized equations of motion, we calculate the one particle irreducible functions which are known to be divergent by naive power counting at the one loop order.Comment: 23 pages, LaTeX, 5 Encapsulated Postscript figures. Improved and revised version, to appear in Phys. Rev.
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