1,010 research outputs found

    Fatty Acid-Induced Lipotoxicity in Pancreatic Beta-Cells During Development of Type 2 Diabetes

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    Type 2 diabetes is caused by chronic insulin resistance and progressive decline in beta-cell function. Optimal beta-cell function and mass is essential for glucose homeostasis and beta-cell impairment leads to the development of diabetes. Elevated levels of circulating fatty acids (FAs) and disturbances in lipid metabolism regulation are associated with obesity, and they are major factors influencing the increase in the incidence of type 2 diabetes. Chronic free FA (FFA) treatment induces insulin resistance and beta-cell dysfunction; therefore, reduction of elevated plasma FFA levels might be an important therapeutic target in obesity and type 2 diabetes. Lipid signals via receptors, and intracellular mechanisms are involved in FFA-induced apoptosis. In this paper, we discuss lipid actions in beta cells, including effects on metabolic pathways and stress responses, to help further understand the molecular mechanisms of lipotoxicity-induced type 2 diabetes

    ATIC and PAMELA Results on Cosmic e^\pm Excesses and Neutrino Masses

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    Recently the ATIC and PAMELA collaborations released their results which show the abundant e^\pm excess in cosmic rays well above the background, but not for the \bar{p}. Their data if interpreted as the dark matter particles' annihilation imply that the new physics with the dark matter is closely related to the lepton sector. In this paper we study the possible connection of the new physics responsible for the cosmic e^\pm excesses to the neutrino mass generation. We consider a class of models and do the detailed numerical calculations. We find that these models can natually account for the ATIC and PAMELA e^\pm and \bar{p} data and at the same time generate the small neutrino masses.Comment: 7 pages, 5 figures. Published version with minor corrections and more reference

    Electrochemical properties and durability of in-situ composite cathodes with SmBa0.5Sr0.5Co2O5+δ for metal supported solid oxide fuel cells

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    The authors are grateful for the support of the Basic Science Research Program, part of the National Research Foundation of Korea (NRF), funded by the Ministry of Science, ICT and Future Planning (No. 2014R1A1A1004163).The electrochemical properties and long-term performance of an in-situ composite cathode comprised of SmBa0.5Sr0.5Co2O5+δ (SBSCO) and Ce0.9Gd0.1O2−δ (CGO91) are investigated for metal supported solid oxide fuel cell (MS-SOFC) application. The Area Specific Resistance (ASR) of an in-situ composite cathode comprised of 50 wt% of SBSCO and 50 wt% of CGO91 (SBSCO:50) is 0.031 Ω cm2 in the first stage of measurement at 700 °C; this value of ASR increases to 0.138 Ω cm2 after 1000 h. The ASR of SBSCO:50 (in-situ sample at 750 °C) is 0.014 Ω cm2 at the initial stage of measurement; the increase of ASR after 1000 h at 750 °C is only 0.067 Ω cm2. These results suggest that the optimum temperature for in-situ firing of an SBSCO:50 cathode sample of MS-SOFC is higher than 700 °C, ideally around 750 °C.PostprintPeer reviewe

    CagA-producing Helicobacter pylori and increased risk of gastric cancer: a nested case–control study in Korea

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    In a nested-case control study of 100 cases of gastric cancer and 400 matched controls in relation to virulence factors of Helicobacter pylori in a Korean cohort, CagA seropositivity was significantly associated with a higher risk of gastric cancer among H. pylori-infected subjects (OR=3.57, 95% CI 1.05–12.14)

    The Genetic Effect of Copy Number Variations on the Risk of Type 2 Diabetes in a Korean Population

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    BACKGROUND: Unlike Caucasian populations, genetic factors contributing to the risk of type 2 diabetes mellitus (T2DM) are not well studied in Asian populations. In light of this, and the fact that copy number variation (CNV) is emerging as a new way to understand human genomic variation, the objective of this study was to identify type 2 diabetes-associated CNV in a Korean cohort. METHODOLOGY/PRINCIPAL FINDINGS: Using the Illumina HumanHap300 BeadChip (317,503 markers), genome-wide genotyping was performed to obtain signal and allelic intensities from 275 patients with type 2 diabetes mellitus (T2DM) and 496 nondiabetic subjects (Total n = 771). To increase the sensitivity of CNV identification, we incorporated multiple factors using PennCNV, a program that is based on the hidden Markov model (HMM). To assess the genetic effect of CNV on T2DM, a multivariate logistic regression model controlling for age and gender was used. We identified a total of 7,478 CNVs (average of 9.7 CNVs per individual) and 2,554 CNV regions (CNVRs; 164 common CNVRs for frequency>1%) in this study. Although we failed to demonstrate robust associations between CNVs and the risk of T2DM, our results revealed a putative association between several CNVRs including chr15:45994758-45999227 (P = 8.6E-04, P(corr) = 0.01) and the risk of T2DM. The identified CNVs in this study were validated using overlapping analysis with the Database of Genomic Variants (DGV; 71.7% overlap), and quantitative PCR (qPCR). The identified variations, which encompassed functional genes, were significantly enriched in the cellular part, in the membrane-bound organelle, in the development process, in cell communication, in signal transduction, and in biological regulation. CONCLUSION/SIGNIFICANCE: We expect that the methods and findings in this study will contribute in particular to genome studies of Asian populations

    Water-Gated Charge Doping of Graphene Induced by Mica Substrates

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    We report on the existence of water-gated charge doping of graphene deposited on atomically flat mica substrates. Molecular films of water in units of ~0.4 nm-thick bilayers were found to be present in regions of the interface of graphene/mica hetero-stacks prepared by micromechanical exfoliation of kish graphite. The spectral variation of the G and 2D bands, as visualized by Raman mapping, shows that mica substrates induce strong p-type doping in graphene, with hole densities of (9±2)×1012cm(9 \pm 2) \times 1012 cm{-2}$. The ultrathin water films, however, effectively block interfacial charge transfer, rendering graphene significantly less hole-doped. Scanning Kelvin probe microscopy independently confirmed a water-gated modulation of the Fermi level by 0.35 eV, in agreement with the optically determined hole density. The manipulation of the electronic properties of graphene demonstrated in this study should serve as a useful tool in realizing future graphene applications.Comment: 15 pages, 4 figures; Nano Letters, accepted (2012

    Discovery of a novel allelic variant of CYP2C8, CYP2C8∗11, in asian populations and its clinical effect on the rosiglitazone disposition

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    ABSTRACT: The objectives of this study were to identify the genetic variants of CYP2C8, analyze CYP2C8 single nucleotide polymorphisms (SNPs), and characterize their functional consequences in the CYP2C8 substrate drug rosiglitazone in humans. The direct full sequencing of CYP2C8 genomic DNA was performed in a Korean population (n ‫؍‬ 50). A total of 17 CYP2C8 variants including a novel coding variant (E274Stop) were identified. The novel CYP2C8 E274Stop variant was assigned as CYP2C8*11 by the Human Cytochrome P450 (CYP) Allele Nomenclature Committee. Seventeen SNPs were used to characterize linkage disequilibrium, haplotype structures, and haplotype tagging SNPs. Genotyping for CYP2C8*11 in an extended set of Koreans (n ‫؍‬ 400), whites (n ‫؍‬ 100), Han Chinese (n ‫؍‬ 348), Vietnamese (n ‫؍‬ 100), and African Americans (n ‫؍‬ 93) was performed by a newly developed pyrosequencing method. The frequency of CYP2C8*11 was 0.3% in Koreans, 1% in Vietnamese, and 0.14% in Chinese. However, none of the whites or African Americans contained the CYP2C8*11 allele. Subjects with CYP2C8*1/*11 exhibited higher plasma concentration-time profiles of rosiglitazone than those of nine control subjects carrying CYP2C8*1/*1. The area under the concentrationtime curve and peak plasma concentration of rosiglitazone in individuals carrying CYP2C8*1/*11 (n ‫؍‬ 5) were 54 and 34% higher than the mean values observed in the control subjects carrying CYP2C8*1/*1 (P ‫؍‬ 0.015 and P ‫؍‬ 0.025, respectively). In summary, this is the first report to characterize the allele frequency and haplotype distribution of CYP2C8 in a Korean population, and it provides functional analysis of a new variant CYP2C8*11. Our findings suggest that individuals carrying CYP2C8*11, a null allele found in Asians only, may have lower activity for metabolizing CYP2C8 substrate drugs
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