2,265 research outputs found

    Effects of various forms of lipopolysaccharide on the expression of inflammatory mediators and cardiac biomarkers in human cardiac fibroblasts and human coronary smooth muscle cells

    Get PDF
    Inflammation is an important event in the development of vascular diseases such as hypertension, atherosclerosis, and restenosis. The stimulation of lipopolysaccharide (LPS) from bacteria induces the release of critical proinflammatory cytokines that activate potent immune responses which may cause injury of cells in vivo and in vitro. Upon cardiac cell death caused by inflammation, the apoptotic cardiac cells express higher amount of cardiac markers. In this study, the effect of various LPS on human cardiac fibroblasts (HCFs) and human coronary smooth muscle cells (HCSMCs) were evaluated. Various forms of LPS were applied to HCFs and HCSMCs for 24, 48, 72 and 96 h. Proliferation rate of these cells was evaluated after stimulation. The levels of lactate dehydrogenase (LDH), N-terminal pro B-type natriuretic peptide (pro-BNP) and the MB isoenzyme of creatine kinase (CK-MB) were measured by an automation system. Cytokine levels in culture supernatants and extracted protein of cells were mixed and measured with IL-1ÎČ, IL-6 and IL-10 ELISA kits. Significant increase in the proliferation of two cardiac cells (P<0.05) after incubation for 48 and 72 h was noted but not for 24 and 96 h (P>0.05). Cardiac markers and inflammatory cytokines were significantly higher than control at 48 and 72 h (P<0.05), which demonstrated that HCFs and HCMSCs were under inflammation leading to cell injury between 48 and 72 h. LPS is one of the factors giving rise to periodontal diseases, it is also involved in in vitro cardiac cell injury. Therefore, LPS may be used as a bio-marker to monitor local or systemic inflammation.Key words: Lipopolysaccharide, human cardiac fibroblasts, human coronary smooth muscle cell, inflammatory cytokines, cardiac bio-marker

    Significance of somatic mutations and content alteration of mitochondrial DNA in esophageal cancer

    Get PDF
    BACKGROUND: The roles of mitochondria in energy metabolism, the generation of ROS, aging, and the initiation of apoptosis have implicated their importance in tumorigenesis. In this study we aim to establish the mutation spectrum and to understand the role of somatic mtDNA mutations in esophageal cancer. METHODS: The entire mitochondrial genome was screened for somatic mutations in 20 pairs (18 esophageal squamous cell carcinomas, one adenosquamous carcinoma and one adenocarcinoma) of tumor/surrounding normal tissue of esophageal cancers, using temporal temperature gradient gel electrophoresis (TTGE), followed by direct DNA sequencing to identify the mutations. RESULTS: Fourteen somatic mtDNA mutations were identified in 55% (11/20) of tumors analyzed, including 2 novel missense mutations and a frameshift mutation in ND4L, ATP6 subunit, and ND4 genes respectively. Nine mutations (64%) were in the D-loop region. Numerous germline variations were found, at least 10 of them were novel and five were missense mutations, some of them occurred in evolutionarily conserved domains. Using real-time quantitative PCR analysis, the mtDNA content was found to increase in some tumors and decrease in others. Analysis of molecular and other clinicopathological findings does not reveal significant correlation between somatic mtDNA mutations and mtDNA content, or between mtDNA content and metastatic status. CONCLUSION: Our results demonstrate that somatic mtDNA mutations in esophageal cancers are frequent. Some missense and frameshift mutations may play an important role in the tumorigenesis of esophageal carcinoma. More extensive biochemical and molecular studies will be necessary to determine the pathological significance of these somatic mutations

    LHC Predictions from a Tevatron Anomaly in the Top Quark Forward-Backward Asymmetry

    Get PDF
    We examine the implications of the recent CDF measurement of the top-quark forward-backward asymmetry, focusing on a scenario with a new color octet vector boson at 1-3 TeV. We study several models, as well as a general effective field theory, and determine the parameter space which provides the best simultaneous fit to the CDF asymmetry, the Tevatron top pair production cross section, and the exclusion regions from LHC dijet resonance and contact interaction searches. Flavor constraints on these models are more subtle and less severe than the literature indicates. We find a large region of allowed parameter space at high axigluon mass and a smaller region at low mass; we match the latter to an SU(3)xSU(3)/SU(3) coset model with a heavy vector-like fermion. Our scenario produces discoverable effects at the LHC with only 1-2 inverse femtobarns of luminosity at 7-8 TeV. Lastly, we point out that a Tevatron measurement of the b-quark forward-backward asymmetry would be very helpful in characterizing the physics underlying the top-quark asymmetry.Comment: 35 pages, 10 figures, 4 table

    Stop the Top Background of the Stop Search

    Get PDF
    The main background for the supersymmetric stop direct production search comes from Standard Model ttbar events. For the single-lepton search channel, we introduce a few kinematic variables to further suppress this background by focusing on its dileptonic and semileptonic topologies. All are defined to have end points in the background, but not signal distributions. They can substantially improve the stop signal significance and mass reach when combined with traditional kinematic variables such as the total missing transverse energy. Among them, our variable M^W_T2 has the best overall performance because it uses all available kinematic information, including the on-shell mass of both W's. We see 20%-30% improvement on the discovery significance and estimate that the 8 TeV LHC run with 20 fb-1 of data would be able to reach an exclusion limit of 650-700 GeV for direct stop production, as long as the stop decays dominantly to the top quark and a light stable neutralino. Most of the mass range required for the supersymmetric solution of the naturalness problem in the standard scenario can be covered.Comment: 16 pages, 5 figure

    Parental transfer of the antimicrobial protein LBP/BPI protects Biomphalaria glabrata eggs against oomycete infections

    Get PDF
    Copyright: © 2013 Baron et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work was funded by ANR (ANR-07-BLAN-0214 and ANR-12-EMMA-00O7-01), CNRS and INRA. PvW was financially supported by the BBSRC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Peer reviewedPublisher PD

    A simulation study for comparing testing statistics in response-adaptive randomization

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Response-adaptive randomizations are able to assign more patients in a comparative clinical trial to the tentatively better treatment. However, due to the adaptation in patient allocation, the samples to be compared are no longer independent. At large sample sizes, many asymptotic properties of test statistics derived for independent sample comparison are still applicable in adaptive randomization provided that the patient allocation ratio converges to an appropriate target asymptotically. However, the small sample properties of commonly used test statistics in response-adaptive randomization are not fully studied.</p> <p>Methods</p> <p>Simulations are systematically conducted to characterize the statistical properties of eight test statistics in six response-adaptive randomization methods at six allocation targets with sample sizes ranging from 20 to 200. Since adaptive randomization is usually not recommended for sample size less than 30, the present paper focuses on the case with a sample of 30 to give general recommendations with regard to test statistics for contingency tables in response-adaptive randomization at small sample sizes.</p> <p>Results</p> <p>Among all asymptotic test statistics, the Cook's correction to chi-square test (<it>T</it><sub><it>MC</it></sub>) is the best in attaining the nominal size of hypothesis test. The William's correction to log-likelihood ratio test (<it>T</it><sub><it>ML</it></sub>) gives slightly inflated type I error and higher power as compared with <it>T</it><sub><it>MC</it></sub>, but it is more robust against the unbalance in patient allocation. <it>T</it><sub><it>MC </it></sub>and <it>T</it><sub><it>ML </it></sub>are usually the two test statistics with the highest power in different simulation scenarios. When focusing on <it>T</it><sub><it>MC </it></sub>and <it>T</it><sub><it>ML</it></sub>, the generalized drop-the-loser urn (GDL) and sequential estimation-adjusted urn (SEU) have the best ability to attain the correct size of hypothesis test respectively. Among all sequential methods that can target different allocation ratios, GDL has the lowest variation and the highest overall power at all allocation ratios. The performance of different adaptive randomization methods and test statistics also depends on allocation targets. At the limiting allocation ratio of drop-the-loser (DL) and randomized play-the-winner (RPW) urn, DL outperforms all other methods including GDL. When comparing the power of test statistics in the same randomization method but at different allocation targets, the powers of log-likelihood-ratio, log-relative-risk, log-odds-ratio, Wald-type Z, and chi-square test statistics are maximized at their corresponding optimal allocation ratios for power. Except for the optimal allocation target for log-relative-risk, the other four optimal targets could assign more patients to the worse arm in some simulation scenarios. Another optimal allocation target, <it>R</it><sub><it>RSIHR</it></sub>, proposed by Rosenberger and Sriram (<it>Journal of Statistical Planning and Inference</it>, 1997) is aimed at minimizing the number of failures at fixed power using Wald-type Z test statistics. Among allocation ratios that always assign more patients to the better treatment, <it>R</it><sub><it>RSIHR </it></sub>usually has less variation in patient allocation, and the values of variation are consistent across all simulation scenarios. Additionally, the patient allocation at <it>R</it><sub><it>RSIHR </it></sub>is not too extreme. Therefore, <it>R</it><sub><it>RSIHR </it></sub>provides a good balance between assigning more patients to the better treatment and maintaining the overall power.</p> <p>Conclusion</p> <p>The Cook's correction to chi-square test and Williams' correction to log-likelihood-ratio test are generally recommended for hypothesis test in response-adaptive randomization, especially when sample sizes are small. The generalized drop-the-loser urn design is the recommended method for its good overall properties. Also recommended is the use of the <it>R</it><sub><it>RSIHR </it></sub>allocation target.</p

    LHC Coverage of RPV MSSM with Light Stops

    Full text link
    We examine the sensitivity of recent LHC searches to signatures of supersymmetry with R-parity violation (RPV). Motivated by naturalness of the Higgs potential, which would favor light third-generation squarks, and the stringent LHC bounds on spectra in which the gluino or first and second generation squarks are light, we focus on scenarios dominated by the pair production of light stops. We consider the various possible direct and cascade decays of the stop that involve the trilinear RPV operators. We find that in many cases, the existing searches exclude stops in the natural mass range and beyond. However, typically there is little or no sensitivity to cases dominated by UDD operators or LQD operators involving taus. We propose several ideas for searches which could address the existing gaps in experimental coverage of these signals.Comment: 41 pages, 12 figures; v2: included new searches (see footnote 10), minor corrections and improvement

    Rhizome Severing Increases Root Lifespan of Leymus chinensis in a Typical Steppe of Inner Mongolia

    Get PDF
    Root lifespan is an important trait that determines plants' ability to acquire and conserve soil resources. There have been several studies investigating characteristics of root lifespan of both woody and herbaceous species. However, most of the studies have focused on non-clonal plants, and there have been little data on root lifespan for clonal plants that occur widely in temperate grasslands.We investigated the effects of rhizome severing on overall root lifespan of Leymus chinensis, a clonal, dominant grass species in the temperate steppe in northern China, in a 2-year field study using modified rhizotron technique. More specifically, we investigated the effects of rhizome severing on root lifespan of roots born in different seasons and distributed at different soil depths. Rhizome severing led to an increase in the overall root lifespan from 81 to 103 days. The increase in root lifespan exhibited spatial and temporal characteristics such that it increased lifespan for roots distributed in the top two soil layers and for roots born in summer and spring, but it had no effect on lifespan of roots in the deep soil layer and born in autumn. We also examined the effect of rhizome severing on carbohydrate and N contents in roots, and found that root carbohydrate and N contents were not affected by rhizome severing. Further, we found that root lifespan of Stipa krylovii and Artemisia frigida, two dominant, non-clonal species in the temperate steppe, was significantly longer (118 d) than that of L. chinensis (81 d), and this value became comparable to that of L. chinensis under rhizome severing (103 d).We found that root lifespan in dominant, clonal L. chinensis was shorter than for the dominant, non-clonal species of S. krylovii and A. frigida. There was a substantial increase in the root lifespan of L. chinensis in response to severing their rhizomes, and this increase in root lifespan exhibited temporal and spatial characteristics. These findings suggest that the presence of rhizomes is likely to account for the observed short lifespan of clonal plant species in the temperate steppe
    • 

    corecore