521 research outputs found

    Metabolomic profiling of Burkholderia pseudomallei using UHPLC-ESI-Q-TOF-MS reveals specific biomarkers including 4-methyl-5-thiazoleethanol and unique thiamine degradation pathway

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    © 2015 Lau et al.Background: Burkholderia pseudomallei is an emerging pathogen that causes melioidosis, a serious and potentially fatal disease which requires prolonged antibiotics to prevent relapse. However, diagnosis of melioidosis can be difficult, especially in culture-negative cases. While metabolomics represents an uprising tool for studying infectious diseases, there were no reports on its applications to B. pseudomallei. To search for potential specific biomarkers, we compared the metabolomics profiles of culture supernatants of B. pseudomallei (15 strains), B. thailandensis (3 strains), B. cepacia complex (14 strains), P. aeruginosa (4 strains) and E. coli (3 strains), using ultra-high performance liquid chromatography-electrospray ionization-quadruple time-of-flight mass spectrometry (UHPLC-ESI-Q-TOF-MS). Multi- and univariate analyses were used to identify specific metabolites in B. pseudomallei. Results: Principal component and partial-least squares discrimination analysis readily distinguished the metabolomes between B. pseudomallei and other bacterial species. Using multi-variate and univariate analysis, eight metabolites with significantly higher levels in B. pseudomallei were identified. Three of the eight metabolites were identified by MS/MS, while five metabolites were unidentified against database matching, suggesting that they may be potentially novel compounds. One metabolite, m/z 144.048, was identified as 4-methyl-5-thiazoleethanol, a degradation product of thiamine (vitamin B1), with molecular formula C6H9NOS by database searches and confirmed by MS/MS using commercially available authentic chemical standard. Two metabolites, m/z 512.282 and m/z 542.2921, were identified as tetrapeptides, Ile-His-Lys-Asp with molecular formula C22H37N7O7 and Pro-Arg-Arg-Asn with molecular formula C21H39N11O6, respectively. To investigate the high levels of 4-methyl-5-thiazoleethanol in B. pseudomallei, we compared the thiamine degradation pathways encoded in genomes of B. pseudomallei and B. thailandensis. While both B. pseudomallei and B. thailandensis possess thiaminase I which catalyzes degradation of thiamine to 4-methyl-5-thiazoleethanol, thiM, which encodes hydroxyethylthiazole kinase responsible for degradation of 4-methyl-5-thiazoleethanol, is present and expressed in B. thailandensis as detected by PCR/RT-PCR, but absent or not expressed in all B. pseudomallei strains. This suggests that the high 4-methyl-5-thiazoleethanol level in B. pseudomallei is likely due to the absence of hydroxyethylthiazole kinase and hence reduced downstream degradation. Conclusion: Eight novel biomarkers, including 4-methyl-5-thiazoleethanol and two tetrapeptides, were identified in the culture supernatant of B. pseudomallei.published_or_final_versio

    Influence of charge trapping on electroluminescence from Si-nanocrystal light emitting structure

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    We report a study on the influence of charge trapping on electroluminescence (EL) from Si nanocrystal (nc-Si) distributed throughout a 30 nm Si O2 thin film synthesized by Si+ implantation into an oxide film thermally grown on a p -type Si substrate. The electron and hole trapping in the nc-Si located near the indium tin oxide gate and the Si substrate, respectively, cause a reduction in the EL intensity. The reduced EL intensity can be recovered after the trapped charges are released. A partial recovery can be easily achieved by the application of a positive gate voltage or thermal annealing at hot temperatures (e.g., 120 °C) for a short duration. The present study highlights the impact of charging in the nc-Si on the light emission efficiency and its stability of nc-Si light-emitting devices. © 2007 American Institute of Physics.published_or_final_versio

    The Higgs boson in the MSSM in light of the LHC

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    We investigate the expectations for the light Higgs signal in the MSSM in different search channels at the LHC. After taking into account dark matter and flavor constraints in the MSSM with eleven free parameters, we show that the light Higgs signal in the gammaγgamma\gamma channel is expected to be at most at the level of the SM Higgs, while the hbbˉh\rightarrow b\bar{b} from W fusion and/or the hττˉh \rightarrow\tau\bar\tau can be enhanced. For the main discovery mode, we show that a strong suppression of the signal occurs in two different cases: low MAM_A or large invisible width. A more modest suppression is associated with the effect of light supersymmetric particles. Looking for such modification of the Higgs properties and searching for supersymmetric partners and pseudoscalar Higgs offer two complementary probes of supersymmetry.Comment: 19 pages, 8 figure

    Protein profiling in hepatocellular carcinoma by label-free quantitative proteomics in two west african populations.

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    Background Hepatocellular Carcinoma is the third most common cause of cancer related death worldwide, often diagnosed by measuring serum AFP; a poor performance stand-alone biomarker. With the aim of improving on this, our study focuses on plasma proteins identified by Mass Spectrometry in order to investigate and validate differences seen in the respective proteomes of controls and subjects with LC and HCC. Methods Mass Spectrometry analysis using liquid chromatography electro spray ionization quadrupole time-of-flight was conducted on 339 subjects using a pooled expression profiling approach. ELISA assays were performed on four significantly differentially expressed proteins to validate their expression profiles in subjects from the Gambia and a pilot group from Nigeria. Results from this were collated for statistical multiplexing using logistic regression analysis. Results Twenty-six proteins were identified as differentially expressed between the three subject groups. Direct measurements of four; hemopexin, alpha-1-antitrypsin, apolipoprotein A1 and complement component 3 confirmed their change in abundance in LC and HCC versus control patients. These trends were independently replicated in the pilot validation subjects from Nigeria. The statistical multiplexing of these proteins demonstrated performance comparable to or greater than ALT in identifying liver cirrhosis or carcinogenesis. This exercise also proposed preliminary cut offs with achievable sensitivity, specificity and AUC statistics greater than reported AFP averages. Conclusions The validated changes of expression in these proteins have the potential for development into high-performance tests usable in the diagnosis and or monitoring of HCC and LC patients. The identification of sustained expression trends strengthens the suggestion of these four proteins as worthy candidates for further investigation in the context of liver disease. The statistical combinations also provide a novel inroad of analyses able to propose definitive cut-offs and combinations for evaluation of performance

    Size Effect on Failure of Pre-stretched Free-Standing Nanomembranes

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    Free-standing nanomembranes are two-dimensional materials with nanometer thickness but can have macroscopic lateral dimensions. We develop a fracture model to evaluate a pre-stretched free standing circular ultrathin nanomembrane and establish a relation between the energy release rate of a circumferential interface crack and the pre-strain in the membrane. Our results demonstrate that detachment cannot occur when the radius of the membrane is smaller than a critical size. This critical radius is inversely proportional to the Young’s modulus and square of the pre-strain of the membrane

    Hemagglutinin-neuraminidase balance confers respiratory-droplet transmissibility of the Pandemic H1N1 Influenza virus in ferrets

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    Conference Theme: Translating Health Research into Policy and Practice for Health of the PopulationPoster Presentations: Emerging / Infectious Diseases: no. P66-Ab0011published_or_final_versio
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