793 research outputs found

    Non-singular, vacuum, stationary space-times with a negative cosmological constant

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    We construct infinite dimensional families of non-singular stationary space times, solutions of the vacuum Einstein equations with a negative cosmological constant.Comment: minor corrections, an inessential uniqueness claim withdraw

    An unfitted hybrid high-order method for the stokes interface problem

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    We design and analyze a hybrid high-order method on unfitted meshes to approximate the Stokes interface problem. The interface can cut through the mesh cells in a very general fashion. A cell-agglomeration procedure prevents the appearance of small cut cells. Our main results are inf-sup stability and a priori error estimates with optimal convergence rates in the energy norm. Numerical simulations corroborate these results

    Tissue-Targeted CRISPR-Cas9-Mediated Genome Editing of Multiple Homeologs in F0 Generation Xenopus Laevis Embryos

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    Xenopus laevis frogs are a powerful developmental model that enables studies combining classical embryology and molecular manipulation. Because of the large embryo size, ease of microinjection, and ability to target tissues through established fate maps, X. laevis have become the predominant amphibian research model. Given that their allotetraploid genome has complicated the generation of gene knockouts, strategies need to be established for efficient mutagenesis of multiple homeologs to evaluate gene function. Here we describe a protocol to utilize CRISPR-Cas9-mediated genome editing to target either single alleles or multiple alloalleles in F0 X. laevis embryos. A single guide (sg) RNA is designed to target a specific DNA sequence encoding a critical protein domain. To mutagenize a gene with two alloalleles, the sgRNA is designed against a sequence that is common to both homeologs. This sgRNA, along with the Cas9 protein, is microinjected into the zygote to disrupt the genomic sequences in the whole embryo or into a specific blastomere for tissue-targeted effects. Error-prone repair of CRISPR/Cas9 generated DNA double strand breaks leads to insertions and deletions creating mosaic gene lesions within the embryos. The genomic DNA isolated from each mosaic F0 embryo is sequenced, and software is applied to assess the nature of the mutations generated and degree of mosaicism. This protocol enables the knockout of genes within the whole embryo or in specific tissues in F0 X. laevis embryos to facilitate the evaluation of resulting phenotypes

    Pressure vessel with improved impact resistance and method of making the same

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    A composite overwrapped pressure vessel is provided which includes a composite overwrapping material including fibers disposed in a resin matrix. At least first and second kinds of fibers are used. These fibers typically have characteristics of high strength and high toughness to provide impact resistance with increased pressure handling capability and low weight. The fibers are applied to form a pressure vessel using wrapping or winding techniques with winding angles varied for specific performance characteristics. The fibers of different kinds are dispersed in a single layer of winding or wound in distinct separate layers. Layers of fabric comprised of such fibers are interspersed between windings for added strength or impact resistance. The weight percentages of the high toughness and high strength materials are varied to provide specified impact resistance characteristics. The resin matrix is formed with prepregnated fibers or through wet winding. The vessels are formed with or without liners

    Hybrid Wound Filaments for Greater Resistance to Impacts

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    A hybrid material containing wound filaments made of a hybrid of high-strength carbon fibers and poly(phenylene benzobisoxazole) [PBO] fibers is discussed. This hybrid material is chosen in an effort to increase the ability of the pressure vessel to resist damage by low-speed impacts (e.g., dropping of tools on the vessel or bumping of the vessel against hard objects during installation and use) without significantly increasing the weight of the vessel. While the basic concept of hybridizing fibers in filament-wound structures is not new, the use of hybridization to increase resistance to impacts is an innovation, and can be expected to be of interest in the composite-pressure-vessel industry. The precise types and the proportions of the high-strength carbon fibers and the PBO fibers in the hybrid are chosen, along with the filament-winding pattern, to maximize the advantageous effects and minimize the disadvantageous effects of each material. In particular, one seeks to (1) take advantage of the ability of the carbon fibers to resist stress rupture while minimizing their contribution to vulnerability of the vessel to impact damage and (2) take advantage of the toughness of the PBO fibers while minimizing their contribution to vulnerability of the vessel to stress rupture. Experiments on prototype vessels fabricated according to this concept have shown promising results. At the time of reporting the information for this article, research toward understanding and optimizing the performances of PBO fibers so as to minimize their contribution to vulnerability of the pressure vessel to stress rupture had yet to be performed

    Parameters Affecting Continuous In Vitro Culture of Treponema pallidum Strains

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    The bacterium that causes syphilis, Treponema pallidum subsp. pallidum, has now been cultured in vitro continuously for periods exceeding 3 years using a system consisting of coculture with Sf1Ep rabbit epithelial cells in TpCM-2 medium and a low-oxygen environment. In addition, long-term culture of several other syphilis isolates (SS14, Mexico A, UW231B, and UW249B) and the T. pallidum subsp. endemicum Bosnia A strain has been achieved. During in vitro passage, T. pallidum subsp. pallidum exhibited a typical bacterial growth curve with logarithmic and stationary phases. Sf1Ep cells are required for sustained growth and motility; however, high initial Sf1Ep cell numbers resulted in reduced multiplication and survival. Use of Eagle’s minimal essential medium as the basal medium was not effective in sustaining growth of T. pallidum subsp. pallidum beyond the first passage, whereas CMRL 1066 or M199 supported long-term culture, confirming that additional nutrients present in these more complex basal media are required for long-term culture. T. pallidum subsp. pallidum growth was dependent upon the presence of fetal bovine serum, with 20% (vol/vol) being the optimal concentration. Omission of reactive oxygen species scavengers dithiothreitol, d-mannitol, or l-histidine did not dramatically affect survival or growth. Additionally, T. pallidum subsp. pallidum can be successfully cultured in a Brewer jar instead of a specialized low-oxygen incubator. Phosphomycin or amphotericin B can be added to the medium to aid in the prevention of bacterial or fungal contamination, respectively. These results help define the parameters of the T. pallidum subsp. pallidum culture system that are required for sustained, long-term survival and multiplication

    Aggregated proteins in schizophrenia and other chronic mental diseases: DISC1opathies

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    Chronic mental diseases (CMD) like the schizophrenias are progressive diseases of heterogenous but poorly understood biological origin. An imbalance in proteostasis is a hallmark of dysfunctional neurons, leading to impaired clearance and abnormal deposition of protein aggregates. Thus, it can be hypothesized that unbalanced proteostasis in such neurons may also lead to protein aggregates in schizophrenia. These protein aggregates, however, would be more subtle then in the classical neurodegenerative diseases and as such have not yet been detected. The DISC1 (Disrupted-in-schizophrenia 1) gene is considered among the most promising candidate genes for CMD having been identified as linked to CMD in a Scottish pedigree and having since been found to associate to various phenotypes of CMD. We have recently demonstrated increased insoluble DISC1 protein in the cingular cortex in approximately 20% of cases of CMD within the widely used Stanley Medical Research Institute Consortium Collection. Surprisingly, in vitro, DISC1 aggregates were cell-invasive, i.e., purified aggresomes or recombinant DISC1 fragments where internalized at an efficiency comparable to that of α-synuclein. Intracellular DISC1 aggresomes acquired gain-of-function properties in recruiting otherwise soluble proteins such as the candidate schizophrenia protein dysbindin. Disease-associated DISC1 polymorphism S704C led to a higher oligomerization tendency of DISC1. These findings justify classification of DISC1-dependent brain disorders as protein conformational disorders which we have tentatively termed DISC1opathies. The notion of disturbed proteostasis and protein aggregation as a mechanism of mental diseases is thus emerging. The yet unidentified form of neuronal impairment in CMD is more subtle than in the classical neurodegenerative diseases without leading to massive cell death and as such present a different kind of neuronal dysfunctionality, eventually confined to highly selective CNS subpopulations

    Gluing construction of initial data with Kerr-de Sitter ends

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    We construct initial data sets which satisfy the vacuum constraint equa- tions of General Relativity with positive cosmologigal constant. More pre- silely, we deform initial data with ends asymptotic to Schwarzschild-de Sitter to obtain non-trivial initial data with exactly Kerr-de Sitter ends. The method is inspired from Corvino's gluing method. We obtain here a extension of a previous result for the time-symmetric case by Chru\'sciel and Pollack.Comment: 27 pages, 3 figure
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