2,712 research outputs found

    Linear Rank-Width of Distance-Hereditary Graphs

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    We present a characterization of the linear rank-width of distance-hereditary graphs. Using the characterization, we show that the linear rank-width of every n-vertex distance-hereditary graph can be computed in time O(n²⋅log(n)), and a linear layout witnessing the linear rank-width can be computed with the same time complexity. For our characterization, we combine modifications of canonical split decompositions with an idea of [Megiddo, Hakimi, Garey, Johnson, Papadimitriou: The complexity of searching a graph. JACM 1988], used for computing the path-width of trees. We also provide a set of distance-hereditary graphs which contains the set of distance-hereditary vertex-minor obstructions for linear rank-width. The set given in [Jeong, Kwon, Oum: Excluded vertex-minors for graphs of linear rank-width at most k. STACS 2013: 221–232] is a subset of our obstruction set

    Activation of COX-2/PGE2 Promotes Sapovirus Replication via the Inhibition of Nitric Oxide Production.

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    Enteric caliciviruses in the genera Norovirus and Sapovirus are important pathogens that cause severe acute gastroenteritis in both humans and animals. Cyclooxygenases (COXs) and their final product, prostaglandin E2 (PGE2), are known to play important roles in the modulation of both the host response to infection and the replicative cycles of several viruses. However, the precise mechanism(s) by which the COX/PGE2 pathway regulates sapovirus replication remains largely unknown. In this study, infection with porcine sapovirus (PSaV) strain Cowden, the only cultivable virus within the genus Sapovirus, markedly increased COX-2 mRNA and protein levels at 24 and 36 h postinfection (hpi), with only a transient increase in COX-1 levels seen at 24 hpi. The treatment of cells with pharmacological inhibitors, such as nonsteroidal anti-inflammatory drugs or small interfering RNAs (siRNAs) against COX-1 and COX-2, significantly reduced PGE2 production, as well as PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We observed that pharmacological inhibition of COX-2 dramatically increased NO production, causing a reduction in PSaV replication that could be restored by inhibition of nitric oxide synthase via the inhibitor N-nitro-l-methyl-arginine ester. This study identified a pivotal role for the COX/PGE2 pathway in the regulation of NO production during the sapovirus life cycle, providing new insights into the life cycle of this poorly characterized family of viruses. Our findings also reveal potential new targets for treatment of sapovirus infection. IMPORTANCE: Sapoviruses are among the major etiological agents of acute gastroenteritis in both humans and animals, but little is known about sapovirus host factor requirements. Here, using only cultivable porcine sapovirus (PSaV) strain Cowden, we demonstrate that PSaV induced the vitalization of the cyclooxygenase (COX) and prostaglandin E2 (PGE2) pathway. Targeting of COX-1/2 using nonsteroidal anti-inflammatory drugs (NSAIDs) such as the COX-1/2 inhibitor indomethacin and the COX-2-specific inhibitors NS-398 and celecoxib or siRNAs targeting COXs, inhibited PSaV replication. Expression of the viral proteins VPg and ProPol was associated with activation of the COX/PGE2 pathway. We further demonstrate that the production of PGE2 provides a protective effect against the antiviral effector mechanism of nitric oxide. Our findings uncover a new mechanism by which PSaV manipulates the host cell to provide an environment suitable for efficient viral growth, which in turn can be a new target for treatment of sapovirus infection.Wellcome Trust (097997/Z/11/Z); Grant (2014R1A2A2A01004292) of Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT and Future Planning, the Korea Basic Science Institute grant (C33730), and Bio-industry Technology Development Program (315021-04) funded by the Ministry of Agriculture, Food and Rural Affairs, Republic of Korea

    Enhanced Supersymmetry of Nonrelativistic ABJM Theory

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    We study the supersymmetry enhancement of nonrelativistic limits of the ABJM theory for Chern-Simons level k=1,2k=1,2. The special attention is paid to the nonrelativistic limit (known as `PAAP' case) containing both particles and antiparticles. Using supersymmetry transformations generated by the monopole operators, we find additional 2 kinematical, 2 dynamical, and 2 conformal supercharges for this case. Combining with the original 8 kinematical supercharges, the total number of supercharges becomes maximal: 14 supercharges, like in the well-known PPPP limit. We obtain the corresponding super Schr\"odinger algebra which appears to be isomorphic to the one of the PPPP case. We also discuss the role of monopole operators in supersymmetry enhancement and partial breaking of supersymmetry in nonrelativistic limit of the ABJM theory.Comment: 22 pages, references added, version to appear in JHE

    Optimal cut-off criteria for duplex ultrasound for the diagnosis of restenosis in stented carotid arteries: Review and protocol for a diagnostic study

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    Background: Carotid angioplasty with stenting is a relatively new, increasingly used, less-invasive treatment for the treatment of symptomatic carotid artery stenosis. It is being evaluated in ongoing and nearly finished randomized trials. An important factor in the evaluation of stents is the occurrence of in-stent restenosis. An un-stented carotid artery is likely to have a more elastic vessel wall than a stented one, even if stenosis is present. Therefore, duplex ultrasound cut-off criteria for the degrees of an in-stent stenosis, based on blood velocity parameters, are probably different from the established cut-offs used for un-stented arteries. Routine criteria can not be applied to stented arteries but new criteria need to be established for this particular purpose. Methods/Design: Current literature was systematically reviewed. From the selected studies, the following data were extracted: publication year, population size, whether the study was prospective, which reference test was used, and if there was an indication for selection bias and for verification bias in particular. Previous studies often were retrospective, or the reference test (DSA or CTA) was carried out only when a patient was suspected of having restenosis at DUS, which may result in verification bias. Results: In general, the cut-off values are higher than those reported for unstented arteries. Previous studies often were retrospective, or the reference test (DSA or CTA) was carried out only when a patient was suspected of having restenosis at DUS, which may result in verification bias. Discussion: To address the deficiencies of the existing studies, we propose a prospective cohort study nested within the International Carotid Stenting Study (ICSS), an international multi-centre trial in which over 1,700 patients have been randomised between stenting and CEA. In this cohort we will enrol a minimum of 300 patients treated with a stent. All patients undergo regular DUS examination at the yearly follow-up visit according to the ICSS protocol. To avoid verification bias, an additional computed tomography angiography (CTA) will be performed as a reference test in all consecutive patients, regardless of the degree of stenosis on the initial DUS test

    Biochemical properties of Paracoccus denitrificans FnrP:Reactions with molecular oxygen and nitric oxide

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    In Paracoccus denitrificans, three CRP/FNR family regulatory proteins, NarR, NnrR and FnrP, control the switch between aerobic and anaerobic (denitrification) respiration. FnrP is a [4Fe-4S] cluster containing homologue of the archetypal O2 sensor FNR from E. coli and accordingly regulates genes encoding aerobic and anaerobic respiratory enzymes in response to O2, and also NO, availability. Here we show that FnrP undergoes O2-driven [4Fe-4S] to [2Fe-2S] cluster conversion that involves up to 2 O2 per cluster, with significant oxidation of released cluster sulfide to sulfane observed at higher O2 concentrations. The rate of the cluster reaction was found to be ~6-fold lower than that of E. coli FNR, suggesting that FnrP can remain transcriptionally active under microaerobic conditions. This is consistent with a role for FnrP in activating expression of the high O2 affinity cytochrome c oxidase under microaerobic conditions. Cluster conversion resulted in dissociation of the transcriptionally active FnrP dimer into monomers. Therefore, along with E. coli FNR, FnrP belongs to the subset of FNR proteins in which cluster type is correlated with association state. Interestingly, two key charged residues, Arg140 and Asp154, that have been shown to play key roles in the monomer-dimer equilibrium in E. coli FNR are not conserved in FnrP, indicating that different protomer interactions are important for this equilibrium. Finally, the FnrP [4Fe-4S] cluster is shown to undergo reaction with multiple NO molecules, resulting in iron nitrosyl species and dissociation into monomers

    Sex differences in the morphological failure patterns following hip resurfacing arthroplasty

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    <p>Abstract</p> <p>Background</p> <p>Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty.</p> <p>Methods</p> <p>Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n = 133), osteonecrosis (n = 151), the presence of excessive intraosseous lymphocyte infiltration (n = 11), and interface hyperosteoidosis (n = 30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis.</p> <p>Results</p> <p>Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, <it>P </it>for difference = 0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, <it>P </it>for difference = 0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, <it>P </it>for difference = 0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, <it>P </it>for difference = 0.03).</p> <p>Conclusions</p> <p>Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.</p

    Phloroglucinol Inhibits the Bioactivities of Endothelial Progenitor Cells and Suppresses Tumor Angiogenesis in LLC-Tumor-Bearing Mice

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    Background: There is increasing evidence that phloroglucinol, a compound from Ecklonia cava, induces the apoptosis of cancer cells, eventually suppressing tumor angiogenesis. Methodology/Principal Findings: This is the first report on phloroglucinol’s ability to potentially inhibit the functional bioactivities of endothelial progenitor cells (EPCs) and thereby attenuate tumor growth and angiogenesis in the Lewis lung carcinoma (LLC)-tumor-bearing mouse model. Although Phloroglucinol did not affect their cell toxicity, it specifically inhibited vascular endothelial growth factor (VEGF) dependent migration and capillary-like tube formation of EPCs. Our matrigel plug assay clearly indicated that orally injected phloroglucinol effectively disrupts VEGF-induced neovessel formation. Moreover, we demonstrated that when phloroglucinol is orally administered, it significantly inhibits tumor growth and angiogenesis as well as CD45 2 /CD34 + progenitor mobilization into peripheral blood in vivo in the LLC-tumorbearing mouse model. Conclusions/Significance: These results suggest a novel role for phloroglucinol: Phloroglucinol might be a modulator of circulating EPC bioactivities, eventually suppressing tumorigenesis. Therefore, phloroglucinol might be a candidat

    On thermodynamics of N=6 superconformal Chern-Simons theory

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    We study thermodynamics of N=6 superconformal Chern-Simons theory by computing quantum corrections to the free energy. We find that in weakly coupled ABJM theory on R(2) x S(1), the leading correction is non-analytic in the 't Hooft coupling lambda, and is approximately of order lambda^2 log(lambda)^3. The free energy is expressed in terms of the scalar thermal mass m, which is generated by screening effects. We show that this mass vanishes to 1-loop order. We then go on to 2-loop order where we find a finite and positive mass squared m^2. We discuss differences in the calculation between Coulomb and Lorentz gauge. Our results indicate that the free energy is a monotonic function in lambda which interpolates smoothly to the N^(3/2) behaviour at strong coupling.Comment: 29 pages. v2: references added. v3: minor changes, references added, published versio
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