189 research outputs found

    Clusters in the Expanse: Understanding and Unbiasing IPv6 Hitlists

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    Network measurements are an important tool in understanding the Internet. Due to the expanse of the IPv6 address space, exhaustive scans as in IPv4 are not possible for IPv6. In recent years, several studies have proposed the use of target lists of IPv6 addresses, called IPv6 hitlists. In this paper, we show that addresses in IPv6 hitlists are heavily clustered. We present novel techniques that allow IPv6 hitlists to be pushed from quantity to quality. We perform a longitudinal active measurement study over 6 months, targeting more than 50 M addresses. We develop a rigorous method to detect aliased prefixes, which identifies 1.5 % of our prefixes as aliased, pertaining to about half of our target addresses. Using entropy clustering, we group the entire hitlist into just 6 distinct addressing schemes. Furthermore, we perform client measurements by leveraging crowdsourcing. To encourage reproducibility in network measurement research and to serve as a starting point for future IPv6 studies, we publish source code, analysis tools, and data.Comment: See https://ipv6hitlist.github.io for daily IPv6 hitlists, historical data, and additional analyse

    Developing Test Methods for Compression after Lightning Strikes

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    Research into residual strength after lightning strike is increasing within the literature. However, standard test methods for measuring residual compressive strength after lightning strikes do not exist. For the first time, a systematic experimental study is undertaken to evaluate modifications necessary to standard Compression After Impact (CAI) specimen geometry and test jig design to induce specimen failure at the lightning damage region. Four laboratory generated lightning strike currents with peak amplitudes ranging from 25 to 100kA have been studied. Test set-up modifications were made considering the scale of the lightning damage and its potential proximity to specimen edges. Specimen geometry and anti-buckling guides were adjusted for each peak current to induce specimen failure at the lightning damage. The Compression After Lightning (CAL) strength was 28% lower than the pristine CAI strength even at a relatively low peak current of 25 kA. This study shows that the standard CAI test setup has the potential for CAL application, however, careful modifications are required depending on the peak amplitude of the applied lightning current waveform

    Characterization of the Ca2+-gated and voltage-dependent k+-channel slo-1 of nematodes and its interaction with emodepside

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    The cyclooctadepsipeptide emodepside and its parent compound PF1022A are broad-spectrum nematicidal drugs which are able to eliminate nematodes resistant to other anthelmintics. The mode of action of cyclooctadepsipeptides is only partially understood, but involves the latrophilin Lat-1 receptor and the voltage- and calcium-activated potassium channel Slo-1. Genetic evidence suggests that emodepside exerts its anthelmintic activity predominantly through Slo-1. Indeed, slo-1 deficient Caenorhabditis elegans strains are completely emodepside resistant. However, direct effects of emodepside on Slo-1 have not been reported and these channels have only been characterized for C. elegans and related Strongylida. Molecular and bioinformatic analyses identified full-length Slo-1 cDNAs of Ascaris suum, Parascaris equorum, Toxocara canis, Dirofilaria immitis, Brugia malayi, Onchocerca gutturosa and Strongyloides ratti. Two paralogs were identified in the trichocephalids Trichuris muris, Trichuris suis and Trichinella spiralis. Several splice variants encoding truncated channels were identified in Trichuris spp. Slo-1 channels of trichocephalids form a monophyletic group, showing that duplication occurred after the divergence of Enoplea and Chromadorea. To explore the function of a representative protein, C. elegans Slo-1a was expressed in Xenopus laevis oocytes and studied in electrophysiological (voltage-clamp) experiments. Incubation of oocytes with 1-10 µM emodepside caused significantly increased currents over a wide range of step potentials in the absence of experimentally increased intracellular Ca2+, suggesting that emodepside directly opens C. elegans Slo-1a. Emodepside wash-out did not reverse the effect and the Slo-1 inhibitor verruculogen was only effective when applied before, but not after, emodepside. The identification of several splice variants and paralogs in some parasitic nematodes suggests that there are substantial differences in channel properties among species. Most importantly, this study showed for the first time that emodepside directly opens a Slo-1 channel, significantly improving the understanding of the mode of action of this drug class

    Degrees of Freedom and the Deconfining Phase Transition

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    There is a sharp increase in the relative number of degrees of freedom at the deconfining phase transition. Characterizing this increase using the Polyakov Loop model, we find that for a nearly second order deconfining phase transition, the medium-induced energy loss turns on rapidly above T_c, proportional to the relative number of degrees of freedom. Further, energy loss is logarithmically dependent on the screening mass, and thus is sensitive to nearly critical scattering.Comment: 5 pages, REVTEX, no figures; sensitivity of energy loss to the screening mass and to nearly critical scattering adde

    Biogenesis of mitochondrial porin

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    We review here the present knowledge about the pathway of import and assembly of porin into mitochondria and compare it to those of other mitochondrial proteins. Porin, like all outer mitochondrial membrane proteins studied so far is made as a precursor without a cleavble lsquosignalrsquo sequence; thus targeting information must reside in the mature sequence. At least part of this information appears to be located at the amino-terminal end of the molecule. Transport into mitochondria can occur post-translationally. In a first step, the porin precursor is specifically recognized on the mitochondrial surface by a protease sensitive receptor. In a second step, porin precursor inserts partially into the outer membrane. This step is mediated by a component of the import machinery common to the import pathways of precursor proteins destined for other mitochondrial subcompartments. Finally, porin is assembled to produce the functional oligomeric form of an integral membrane protein wich is characterized by its extreme protease resistance

    Drug-induced eRF1 degradation promotes readthrough and reveals a new branch of ribosome quality control.

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    Suppression of premature termination codons (PTCs) by translational readthrough is a promising strategy to treat a wide variety of severe genetic diseases caused by nonsense mutations. Here, we present two potent readthrough promoters-NVS1.1 and NVS2.1-that restore substantial levels of functional full-length CFTR and IDUA proteins in disease models for cystic fibrosis and Hurler syndrome, respectively. In contrast to other readthrough promoters that affect stop codon decoding, the NVS compounds stimulate PTC suppression by triggering rapid proteasomal degradation of the translation termination factor eRF1. Our results show that this occurs by trapping eRF1 in the terminating ribosome, causing ribosome stalls and subsequent ribosome collisions, and activating a branch of the ribosome-associated quality control network, which involves the translational stress sensor GCN1 and the catalytic activity of the E3 ubiquitin ligases RNF14 and RNF25

    Mitochondrial protein import

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