95 research outputs found

    Short Paths on the Voronoi Graph and Closest Vector Problem with Preprocessing

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    Improving on the Voronoi cell based techniques of [28, 24], we give a Las Vegas eO (2n) expected time and space algo- rithm for CVPP (the preprocessing version of the Closest Vector Problem, CVP). This improves on the eO (4n) deter- ministic runtime of the Micciancio Voulgaris algorithm [24] (henceforth MV) for CVPP 1 at the cost of a polynomial amount of randomness (which only aects runtime, not cor- rectness). As in MV, our algorithm proceeds by computing a short path on the Voronoi graph of the lattice, where lattice points are adjacent if their Voronoi cells share a common facet, from the origin to a closest lattice vector. Our main technical contribution is a randomized procedure that, given the Voronoi relevant vectors of a lattice { the lattice vectors inducing facets of the Voronoi cell { as preprocessing, and any \close enough" lattice point to the target, computes a path to a closest lattice vector of expected polynomial size. This improves on the eO (2n) path length given by the MV algorithm. Furthermore, as in MV, each edge of the path can be computed using a single iteration over the Voronoi relevant vectors. As a byproduct of our work, we also give an optimal relationship between geometric and path distance on the Voronoi graph, which we believe to be of independent interest

    A facility for the test of large area muon chambers at high rates

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    Operation of large area muon detectors at the future Large Hadron Collider (LHC) will be characterized by large sustained hit rates over the whole area, reaching the range of kHz/\scm. We describe a dedicated test zone built at CERN to test the performance and the aging of the muon chambers currently under development. A radioactive source delivers photons causing the sustained rate of random hits, while a narrow beam of high energy muons is used to directly calibrate the detector performance. A system of remotely controlled lead filters serves to vary the rate of photons over four orders of magnitude, to allow the study of performance as a function of rate

    Hedgehog-interacting protein is highly expressed in endothelial cells but down-regulated during angiogenesis and in several human tumors

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    BACKGROUND: The Hedgehog (Hh) signaling pathway regulates a variety of developmental processes, including vasculogenesis, and can also induce the expression of pro-angiogenic factors in fibroblasts postnatally. Misregulation of the Hh pathway has been implicated in a variety of different types of cancer, including pancreatic and small-cell lung cancer. Recently a putative antagonist of the pathway, Hedgehog-interacting protein (HIP), was identified as a Hh binding protein that is also a target of Hh signaling. We sought to clarify possible roles for HIP in angiogenesis and cancer. METHODS: Inhibition of Hh signaling by HIP was assayed by measuring the induction of Ptc-1 mRNA in TM3 cells treated with conditioned medium containing Sonic hedgehog (Shh). Angiogenesis was assayed in vitro by EC tube formation on Matrigel. Expression of HIP mRNA was assayed in cells and tissues by Q-RT-PCR and Western blot. HIP expression in human tumors or mouse xenograft tumors compared to normal tissues was assayed by Q-RT-PCR or hybridization of RNA probes to a cancer profiling array. RESULTS: We show that Hedgehog-interacting protein (HIP) is abundantly expressed in vascular endothelial cells (EC) but at low or undetectable levels in other cell types. Expression of HIP in mouse epithelial cells attenuated their response to Shh, demonstrating that HIP can antagonize Hh signaling when expressed in the responding cell, and supporting the hypothesis that HIP blocks Hh signaling in EC. HIP expression was significantly reduced in tissues undergoing angiogenesis, including PC3 human prostate cancer and A549 human lung cancer xenograft tumors, as well as in EC undergoing tube formation on Matrigel. HIP expression was also decreased in several human tumors of the liver, lung, stomach, colon and rectum when compared to the corresponding normal tissue. CONCLUSION: These results suggest that reduced expression of HIP, a naturally occurring Hh pathway antagonist, in tumor neo-vasculature may contribute to increased Hh signaling within the tumor and possibly promote angiogenesis

    Deconstructing the Late Phase of Vimentin Assembly by Total Internal Reflection Fluorescence Microscopy (TIRFM)

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    Quantitative imaging of intermediate filaments (IF) during the advanced phase of the assembly process is technically difficult, since the structures are several µm long and therefore they exceed the field of view of many electron (EM) or atomic force microscopy (AFM) techniques. Thereby quantitative studies become extremely laborious and time-consuming. To overcome these difficulties, we prepared fluorescently labeled vimentin for visualization by total internal reflection fluorescence microscopy (TIRFM). In order to investigate if the labeling influences the assembly properties of the protein, we first determined the association state of unlabeled vimentin mixed with increasing amounts of labeled vimentin under low ionic conditions by analytical ultracentrifugation. We found that bona fide tetrameric complexes were formed even when half of the vimentin was labeled. Moreover, we demonstrate by quantitative atomic force microscopy and electron microscopy that the morphology and the assembly properties of filaments were not affected when the fraction of labeled vimentin was below 10%. Using fast frame rates we observed the rapid deposition of fluorescently labeled IFs on glass supports by TIRFM in real time. By tracing their contours, we have calculated the persistence length of long immobilized vimentin IFs to 1 µm, a value that is identical to those determined for shorter unlabeled vimentin. These results indicate that the structural properties of the filaments were not affected significantly by the dye. Furthermore, in order to analyze the late elongation phase, we mixed long filaments containing either Alexa 488- or Alexa 647-labeled vimentin. The ‘patchy’ structure of the filaments obtained unambiguously showed the elongation of long IFs through direct end-to-end annealing of individual filaments

    Nevoid basal cell carcinoma syndrome (Gorlin syndrome)

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    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms

    Xenobiotic-metabolizing enzymes in the skin of rat, mouse, pig, guinea pig, man, and in human skin models

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    Short Paths on the Voronoi Graph and Closest Vector Problem with Preprocessing

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    Improving on the Voronoi cell based techniques of [28, 24], we give a Las Vegas eO (2n) expected time and space algo- rithm for CVPP (the preprocessing version of the Closest Vector Problem, CVP). This improves on the eO (4n) deter- ministic runtime of the Micciancio Voulgaris algorithm [24] (henceforth MV) for CVPP 1 at the cost of a polynomial amount of randomness (which only aects runtime, not cor- rectness). As in MV, our algorithm proceeds by computing a short path on the Voronoi graph of the lattice, where lattice points are adjacent if their Voronoi cells share a common facet, from the origin to a closest lattice vector. Our main technical contribution is a randomized procedure that, given the Voronoi relevant vectors of a lattice { the lattice vectors inducing facets of the Voronoi cell { as preprocessing, and any \close enough" lattice point to the target, computes a path to a closest lattice vector of expected polynomial size. This improves on the eO (2n) path length given by the MV algorithm. Furthermore, as in MV, each edge of the path can be computed using a single iteration over the Voronoi relevant vectors. As a byproduct of our work, we also give an optimal relationship between geometric and path distance on the Voronoi graph, which we believe to be of independent interest

    Unusual interaction of 1-vinyl-4,5,6,7-tetrahydro-4,5,7-trimethylpyrrolo[3,2-c]pyridine with tetracyanoethylene

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    Synthesis of 2-R-4,5,7-trimethyl-1-vinyl-4,5,6,7-tetrahydropyrrolo[3,2-c] pyridines

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    The synthesis of 1-vinyltetrahydropyrrolo[3,2-c]pyridines substituted at C(2) has been accomplished, based on 4,5,7-trimethyl-1-vinyl-4,5,6,7- tetrahydropyrrolo[3,2-c]pyridine and its 2-formyl-substituted derivative. © 2004 Springer Science+Business Media, Inc
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