765 research outputs found

    Measuring IS Service Quality in the Context of the Service Quality-User Satisfaction Relationship

    Get PDF
    There is little research regarding the relationship between IS service quality and user satisfaction, the most frequently used surrogate for information systems success. The current study is designed to investigate three ways of measuring service quality (i.e., confirmation/disconfirmation, perception-only, and overall assessment) and shed light on the relationship between service quality and user satisfaction. The results imply that when managers try to measure service quality to improve their service, they have to be cautious in ruling out or selecting one way or another of measuring service quality. The current research also clearly shows that mangers have to take care of the service quality to enhance user satisfaction. The models and results are discussed

    Domestic policies for climate change

    Get PDF
    노트 : The Asia Climate Change Policy ForumThe Australian National Universit

    Role of Transcription Factor Modifications in the Pathogenesis of Insulin Resistance

    Get PDF
    Non-alcoholic fatty liver disease (NAFLD) is characterized by fat accumulation in the liver not due to alcohol abuse. NAFLD is accompanied by variety of symptoms related to metabolic syndrome. Although the metabolic link between NAFLD and insulin resistance is not fully understood, it is clear that NAFLD is one of the main cause of insulin resistance. NAFLD is shown to affect the functions of other organs, including pancreas, adipose tissue, muscle and inflammatory systems. Currently efforts are being made to understand molecular mechanism of interrelationship between NAFLD and insulin resistance at the transcriptional level with specific focus on post-translational modification (PTM) of transcription factors. PTM of transcription factors plays a key role in controlling numerous biological events, including cellular energy metabolism, cell-cycle progression, and organ development. Cell type- and tissue-specific reversible modifications include lysine acetylation, methylation, ubiquitination, and SUMOylation. Moreover, phosphorylation and O-GlcNAcylation on serine and threonine residues have been shown to affect protein stability, subcellular distribution, DNA-binding affinity, and transcriptional activity. PTMs of transcription factors involved in insulin-sensitive tissues confer specific adaptive mechanisms in response to internal or external stimuli. Our understanding of the interplay between these modifications and their effects on transcriptional regulation is growing. Here, we summarize the diverse roles of PTMs in insulin-sensitive tissues and their involvement in the pathogenesis of insulin resistance

    Active site phosphoryl groups in the biphosphorylated phosphotransferase complex reveal dynamics in a millisecond time scale

    Get PDF
    AbstractThe N-terminal domain of Enzyme I (EIN) and phosphocarrier HPr can form a biphosphorylated complex when they are both phosphorylated by excess cellular phosphoenolpyruvate. Here we show that the electrostatic repulsion between the phosphoryl groups in the biphosphorylated complex results in characteristic dynamics at the active site in a millisecond time scale. The dynamics is localized to phospho-His15 and the stabilizing backbone amide groups of HPr, and does not impact on the phospho-His189 of EIN. The dynamics occurs with the kex of ∼500s−1 which compares to the phosphoryl transfer rate of ∼850s−1 between EIN and HPr. The conformational dynamics in HPr may be important for its phosphotransfer reactions with multiple partner proteins.Structured summary of protein interactionsEIN and HPr bind by nuclear magnetic resonance (View Interaction)

    Antimicrobial Effect of 7-O-Butylnaringenin, a Novel Flavonoid, and Various Natural Flavonoids against Helicobacter pylori Strains

    Get PDF
    Abstract: The antimicrobial effect of a novel flavonoid (7-O-butylnaringenin) on Helicobacter pylori 26695, 51, and SS1 strains and its inhibitory effect on the urease activity of the strains were evaluated and compared with those of several natural flavonoids. First, various flavonoids were screened for antimicrobial activities using the paper disc diffusion method. Hesperetin and naringenin showed the strongest antimicrobial effects among the natural flavonoids tested, and thus hesperetin and naringenin were selected for comparison with 7-O-butylnaringenin. The antimicrobial effect of 7-O-butylnaringenin was greater than that of the hesperetin and naringenin. H. pylori 51 was more sensitive to 7-O-butylnaringenin (2 log reduction of colony forming units, p \u3c 0.05) than the other two strains at 200 μM. 7-O-Butylnaringenin also showed the highest inhibitory effect against urease activity of H. pylori. Morphological changes of H. pylori 26695 treated with these flavonoids indicated that both hesperetin and 7-O-butylnaringenin at 200 μM damaged the cell membranes

    Anti-Inflammatory Effects of Bangpungtongsung-San, a Traditional Herbal Prescription

    Get PDF
    Bangpungtongsung-san (BPTS), a traditional oriental herbal prescription, is widely used for expelling wind, draining heat, and providing general improvement to the immune system. In this study, we investigated the effects of BPTS on induction of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), proinflammatory cytokines, nuclear factor-kappa B (NF-κB), and mitogen-activated protein kinases (MAPKs) in lipopolysaccharide- (LPS- ) stimulated Raw 264.7 cells, and on paw edema in rats. At concentrations of 0.5, 0.75, and 1 mg/mL, treatment with BPTS inhibited levels of expression of LPS-induced NF-κB and MAPKs (ERK, JNK, and p38) as well as production of proinflammatory mediators, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor-α (TNF-α), and interleukin-6 (IL-6) by LPS. These results suggest that BPTS may exert anti-inflammatory effects via reduction of proinflammatory mediators, including NO, PGE2, TNF-α, and IL-6 through suppression of the signaling pathways of NF-κB and MAPKs in LPS-induced macrophages. In addition, using the carrageenan-induced paw edema assay, an antiedema effect of BPTS was observed in rats. These findings may provide scientific evidence validating the use of BPTS in treatment of patients with heat syndrome in Korean oriental medicine

    Effects of Hot rolling Reduction on Microstructural Evolution and Mechanical Properties of 1.25Cr-1Mo-0.5V-0.3C Steel for High-Speed Rail Brake Discs

    Get PDF
    In this study, the effect of rolling of 1.25Cr-1Mo-0.5V-0.3C American Iron and Steel Institute 4340 modified steel for highspeed railway brake discs on the microstructure and mechanical properties was investigated. The materials were hot-rolled at 0%, 51%, and 66% reduction ratios, and then analyzed by optical microscopy, scanning electron microscopy, and electron backscattering diffraction (EBSD). needle-shaped ferrite block morphology in bainite varied with the rolling ratio. EBSD analysis reveals dynamic recovery and dynamic recrystallization, affected ferrite block boundaries and dislocation densities during rolling. Mechanical tests showed that hardness, toughness and elongation increase at higher rolling reduction ratio, while strength remained relatively constant. In particular, the impact toughness increased almost twice from the level of 70 J in S1 (0% reduction) to the level of 130 J in S3 (66% reduction). These results showed that the hot rolling can significantly improve the strength and toughness combination of cast brake discs material

    Mechanisms of Acquired Resistance to AZD9291 A Mutation-Selective, Irreversible EGFR Inhibitor

    Get PDF
    IntroductionAZD9291, a third-generation and mutation-selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is active against patients with EGFRT790M-mutant non–small-cell lung cancer (NSCLC) who failed prior treatment with EGFR TKIs. However, acquired resistance to AZD9291 is inevitable. In this study, we identified the mechanisms of acquired resistance to AZD9291 in EGFRT790M-mutant NSCLC.MethodsFour NSCLC patients with both an EGFR exon 19 deletion and the EGFRT790M mutation after developing acquired resistance to first-generation EGFR TKIs received AZD9291 at doses of 20 to 80 mg/day in a phase I trial (NCT01802632). Paired tumor samples before and after treatment were obtained to evaluate EGFR modifications, alternative pathway activation, and histologic transformation. Genetic alterations were analyzed using Sanger sequencing, fluorescence in situ hybridization, real-time polymerase chain reaction, and targeted exome sequencing.ResultsAll four patients achieved a partial response (median duration of response, 9 months [range, 9–11 months]) and subsequently showed resistance to AZD9291. EGFRT790M-mutant clones depopulated AZD9291-resistant tumors to below 1% (baseline, 14%–36%) in three patients with progression: one with the loss of EGFRLREAT747del/T790M-double mutant clones and two accompanied by transformation to small-cell carcinoma and focal fibroblast growth factor receptor 1 (FGFR1) amplification, respectively. EGFRT790M-mutant clones remained and the EGFR ligand was overexpressed in one patient with focal progression to AZD9291.ConclusionAcquired resistance mechanisms of AZD9291 in patients with EGFRT790M-mutant NSCLC who failed treatment with first-generation EGFR TKIs include the loss of EGFRT790M-mutant clones plus alternative pathway activation or histologic transformation and EGFR ligand–dependent activation
    corecore