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      • Genetic dissection of the biosynthetic route to gentamicin A2 by heterologous expression of its minimal gene set

        Park, J. W.,Hong, J. S. J.,Parajuli, N.,Jung, W. S.,Park, S. R.,Lim, S.-K.,Sohng, J. K.,Yoon, Y. J. Proceedings of the National Academy of Sciences 2008 PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF Vol.105 No.24

        <P>Since the first use of streptomycin as an effective antibiotic drug in the treatment of tuberculosis, aminoglycoside antibiotics have been widely used against a variety of bacterial infections for over six decades. However, the pathways for aminoglycoside biosynthesis still remain unclear, mainly because of difficulty in genetic manipulation of actinomycetes producing this class of antibiotics. Gentamicin belongs to the group of 4,6-disubstituted aminoglycosides containing a characteristic core aminocyclitol moiety, 2-deoxystreptamine (2-DOS), and the recent discovery of its biosynthetic gene cluster in Micromonospora echinospora has enabled us to decipher its biosynthetic pathway. To determine the minimal set of genes and their functions for the generation of gentamicin A(2), the first pseudotrisaccharide intermediate in the biosynthetic pathway for the gentamicin complex, various sets of candidate genes from M. echinospora and other related aminoglycoside-producing strains were introduced into a nonaminoglycoside producing strain of Streptomyces venezuelae. Heterologous expression of different combinations of putative 2-DOS biosynthetic genes revealed that a subset, gtmB-gtmA-gacH, is responsible for the biosynthesis of this core aminocyclitol moiety of gentamicin. Expression of gtmG together with gtmB-gtmA-gacH led to production of 2'-N-acetylparomamine, demonstrating that GtmG acts as a glycosyltransferase that adds N-acetyl-d-glucosamine (GLcNA) to 2-DOS. Expression of gtmM in a 2'-N-acetylparomamine-producing recombinant S. venezuelae strain generated paromamine. Expression of gtmE in an engineered paromamine-producing strain of S. venezuelae successfully generated gentamicin A(2), indicating that GtmE is another glycosyltransferase that attaches d-xylose to paromamine. These results represent in vivo evidence elucidating the complete biosynthetic pathway of the pseudotrisaccharide aminoglycoside.</P>

      • Impact of low dose atorvastatin on development of new-onset diabetes mellitus in Asian population: Three-year clinical outcomes

        Park, J.Y.,Rha, S.W.,Choi, B.,Choi, J.W.,Ryu, S.K.,Kim, S.,Noh, Y.K.,Choi, S.Y.,Akkala, R.G.,Li, H.,Ali, J.,Xu, S.,Ngow, H.A.,Lee, J.J.,Lee, G.N.,Kim, J.,Lee, S.,Na, J.O.,Choi, C.U.,Lim, H.E.,Kim, J.W Elsevier/North-Holland Biomedical Press 2015 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.184 No.-

        Background: High dose atorvastatin is known to be associated with new onset diabetes mellitus (NODM) in patients with high risk for developing diabetes mellitus (DM). However, low dose atorvastatin is more commonly used as compared with high dose atorvastatin. The aim of this study is to investigate the impact of low dose atorvastatin (LDA, 10mg or 20mg) on the development of NODM up to three years in Asian patients. Methods: From January 2004 to September 2009, we investigated a total of 3566 patients who did not have DM. To adjust for potential confounders, a propensity score matching (PSM) analysis was performed using the logistic regression model. After PSM (C-statistics: 0.851), a total of 818 patients (LDA group, n=409 patients and control group, n=409 patients) were enrolled for analysis. Results: Before PSM, the cumulative incidence of NODM (5.8% vs. 2.1%, p<0.001), myocardial infarction (0.5% vs. 0.1%, p-value=0.007), and major adverse cardio-cerebral event (MACCE, 1.8% vs. 0.7%, p-value=0.012) at three-years were higher in the LAD group. However, after PSM, there was a trend toward higher incidence of NODM (5.9% vs. 3.2%, p=0.064) in the LDA group, but the incidence of MACCE (1.2% vs. 1.5%, p-value=1.000) was similar between the two groups. In multivariable analysis, the LDA administration was tended to be an independent predictor of NODM (OR: 1.99, 95% CI: 1.00-3.98, p-value 0.050). Conclusions: In this study, the use of LDA tended to be a risk factor for NODM in Asian patients and reduced clinical events similar to the control group. However, large-scale randomized controlled trials will be needed to get the final conclusion.

      • KCI등재

        Pesticidal Activity of Environment friendly agricultural materials(EFAMs)

        Park J.H.,Han E.J.,Hong S.J.,Ahn N.H.,Kim Y.K.,Jee H.J. 한국유기농업학회 2011 韓國有機農業學會誌 Vol.19 No.S

        Environment friendly agricultural material products (EFAMs) in current market were evaluated for their insecticidal or acaricidal activities. EFAMs were evaluated against Tetranychus urticae, Plutella xylostella, Myzus persicae and Nilaparvata lugens in spray method. Several EFAMs indicated high control value in spray method. Hatchability of T. urticae was relatively high after EFAM treatment. some materials show high insecticidal activities against P. xylostella larvae but not against eggs. Few meterials showed more than 80% insecticidal activities against M. persicae and N. lugen. The control value of more than half the materials for pest control was lower than 60%. EFAMs containing S. flavescens, neem oil and Rape showed higher control value

      • Control of phonon transport by the formation of the Al2O3 interlayer in Al2O3-ZnO superlattice thin films and their in-plane thermoelectric energy generator performance

        Park, N. W.,Ahn, J. Y.,Park, T. H.,Lee, J. H.,Lee, W. Y.,Cho, K.,Yoon, Y. G.,Choi, C. J.,Park, J. S.,Lee, S. K. Royal Society of Chemistry 2017 Nanoscale Vol.9 No.21

        <P>Recently, significant progress has been made in increasing the figure-of-merit (ZT) of various nanostructured materials, including thin-film and quantum dot superlattice structures. Studies have focused on the size reduction and control of the surface or interface of nanostructured materials since these approaches enhance the thermopower and phonon scattering in quantum and superlattice structures. Currently, bismuth-tellurium-based semiconductor materials are widely employed for thermoelectric (TE) devices such as TE energy generators and coolers, in addition to other sensors, for use at temperatures under 400 K. However, new and promising TE materials with enhanced TE performance, including doped zinc oxide (ZnO) multilayer or superlattice thin films, are also required for designing solid-state TE power generating devices with the maximum output power density and for investigating the physics of in-plane TE generators. Herein, we report the growth of Al2O3/ZnO (AO/ZnO) superlattice thin films, which were prepared by atomic layer deposition (ALD), and the evaluation of their electrical and TE properties. All the in-plane TE properties, including the Seebeck coefficient (S), electrical conductivity (sigma), and thermal conductivity (kappa), of the AO/ZnO superlattice (with a 0.82 nm-thick AO layer) and AO/ZnO films (with a 0.13 nm-thick AO layer) were evaluated in the temperature range 40-300 K, and the measured S, s, and. were -62.4 and -17.5 mu V K-1, 113 and 847 (Omega cm)(-1), and 0.96 and 1.04 W m(-1) K-1, respectively, at 300 K. Consequently, the in-plane TE ZT factor of AO/ZnO superlattice films was found to be similar to 0.014, which is approximately two times more than that of AO/ZnO films (ZT of similar to 0.007) at 300 K. Furthermore, the electrical power generation efficiency of the TE energy generator consisting of four couples of n-AO/ZnO superlattice films and p-Bi0.5Sb1.5Te3 (p-BST) thin-film legs on the substrate was demonstrated. Surprisingly, the output power of the 100 nm-thick n-AO/ZnO superlattice film/p-BST TE energy generator was determined to be similar to 1.0 nW at a temperature difference of 80 K, corresponding to a significant improvement of similar to 130% and similar to 220% compared to the 100 nm-thick AO/ZnO film/p-BST and n-BT/p-BST film generators, respectively, owing to the enhancement of the TE properties, including the power factor of the superlattice film.</P>

      • Effect of contrast-induced nephropathy on cardiac outcomes after use of nonionic isosmolar contrast media during coronary procedure

        Cho, J.Y.,Jeong, M.H.,Hwan Park, S.,Kim, I.S.,Park, K.H.,Sim, D.S.,Yoon, N.S.,Yoon, H.J.,Park, H.W.,Hong, Y.J.,Kim, J.H.,Ahn, Y.,Cho, J.G.,Park, J.C.,Kang, J.C. Japanese College of Cardiology 2010 Journal of cardiology Vol.56 No.3

        Contrast-induced nephropathy (CIN) has been increasing and seems to be associated with clinical outcomes in ischemic heart disease. This study aimed to assess the incidence, predictors, and cardiac outcomes of CIN when nonionic isosmolar contrast media (iodixanol, Visipaque<SUP>(</SUP>R), GE Healthcare, Cork, Ireland) was used. Between January 2005 and July 2008, 510 patients (69.2+/-9.0 years of age, 384 men) undergoing diagnostic coronary angiography (CAG) or percutaneous coronary intervention (PCI) were divided into two groups according to the development of CIN (CIN group: n=74; non-CIN group: n=436). CIN developed in 74 patients (14.5%). They were more likely to have diabetes (55.4% vs. 42.9%, p=0.045), decreased left ventricular ejection fraction (LVEF) (50.1+/-12.6% vs. 57.7+/-13.9%, p<0.001), and lower baseline hematocrit level (32.4+/-5.3% vs. 36.6+/-5.5%, p<0.001). Multiple logistic regression analysis revealed baseline hematocrit (odds ratio 0.900, 95% confidence interval 0.851-0.952, p<0.001), decreased LVEF (odds ratio 0.967, 95% confidence interval 0.949-0.986, p=0.001), and baseline creatinine level (odds ratio 2.317, 95% confidence interval 1.252-4.286, p=0.007) as independent predictors of CIN. At 1-year follow-up, patients with CIN were found to have more adverse outcomes than without CIN in Cox proportional hazards analysis (hazard ratio 13.068, 95% confidence interval 2.425-70.434, p=0.003). CIN was mostly associated with baseline creatinine level rather than CM amount using nonionic isosmolar CM. We found that patients with CIN had worse event-free survival than patients without CIN after multifactorial adjustment.

      • Effects of the novel angiotensin II receptor type I antagonist, fimasartan on myocardial ischemia/reperfusion injury

        Han, J.,Park, S.J.,Thu, V.T.,Lee, S.R.,Long, L.T.,Kim, H.K.,Kim, N.,Park, S.W.,Jeon, E.S.,Kim, E.J.,Yoon, C.H.,Cho, G.Y.,Choi, D.J. Elsevier/North-Holland Biomedical Press 2013 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.168 No.3

        Background: The aim of this study was to investigate the cardioprotective effect of fimasartan, a newly developed angiotensin II receptor type I blocker (ARB), against myocardial ischemia/reperfusion (I/R) injury and to identify the mechanism by which it reduces mitochondrial damage. Methods: Fimasartan was administered intravenously to Sprague-Dawley rats (3mg/kg), cardiomyocytes (50μM), and H9c2 cells (50μM) before ischemia or hypoxia. Myocardial infarction (MI), echocardiograms, DNA fragmentation, terminal deoxynucleotidyl transferase-mediated dUTP in situ nick-end labeling, immunoblotting, oxygen consumption, confocal microscopic appearance, and L-type Ca<SUP>2+</SUP> current (I<SUB>Ca,L</SUB>) were then assessed. Results: Fimasartan pretreatment remarkably reduced the rate of MI and improved cardiac performance well after I/R (n=9/group). Fimasartan also reduced apoptotic cell death both in vivo and in hypoxia/reoxygenation (H/R)-treated H9c2 cells (n=5~8/group). H/R-induced mitochondrial O<SUB>2</SUB><SUP>-</SUP> production and collapse of membrane potential were markedly attenuated in fimasartan-treated cardiomyocytes (n=4~6/group). Additionally, mitochondrial Ca<SUP>2+</SUP> overload during reoxygenation was suppressed by fimasartan (n=4~6/group), and this was found to be possibly related to the inhibition of I<SUB>Ca,L</SUB> and mitochondrial Ca<SUP>2+</SUP> uniporter. Furthermore, fimasartan pretreatment increased phosphorylations of Akt and glycogen synthase kinase-3β (n=5~7/group), decreased pro-apoptotic p53 levels, and increased anti-apoptotic Bcl-2 levels (n=4) during reperfusion. Conclusions: Fimasartan preconditioning has the potential to modulate Bcl-2 and suppress I/R-induced Ca<SUP>2+</SUP> overload by inhibiting I<SUB>Ca,L</SUB> and MCU. These beneficial effects could prevent the mitochondrial dysfunction and apoptosis accompanied by I/R.

      • SCISCIESCOPUS

        Direct analysis of site-specific N-glycopeptides of serological proteins in dried blood spot samples

        Choi, N. Y.,Hwang, H.,Ji, E. S.,Park, G. W.,Lee, J. Y.,Lee, H. K.,Kim, J. Y.,Yoo, J. S. Springer Science + Business Media 2017 Analytical and Bioanalytical Chemistry Vol.409 No.21

        <P>Dried blood spot (DBS) samples have a number of advantages, especially with respect to ease of collection, transportation, and storage and to reduce biohazard risk. N-glycosylation is a major post-translational modification of proteins in human blood that is related to a variety of biological functions, including metastasis, cell-cell interactions, inflammation, and immunization. Here, we directly analyzed tryptic N-glycopeptides from glycoproteins in DBS samples using liquid chromatography-tandem mass spectrometry (LC-MS/MS) without centrifugation of blood samples, depletion of major proteins, desalting of tryptic peptides, and enrichment of N-glycopeptides. Using this simple method, we identified a total of 41 site-specific N-glycopeptides from 16 glycoproteins in the DBS samples, from immunoglobulin gamma 1 (IgG-1, 10 mg/mL) down to complement component C7 (50 mu g/mL). Of these, 32 N-glycopeptides from 14 glycoproteins were consistently quantified over 180 days stored at room temperature. The major abundant glycoproteins in the DBS samples were IgG-1 and IgG-2, which contain nine asialo-fucosylated complex types of 16 different N-glycopeptide isoforms. Sialo-non-fucosylated complex types were primarily detected in the other glycoproteins such as alpha-1-acid glycoprotein 1, 2, alpha-1-antitypsin, alpha-2-macroglobulin, haptoglobin, hemopexin, Ig alpha 1, 2 chain C region, kininogen-1, prothrombin, and serotransferrin. We first report the characterization of site-specific N-glycoproteins in DBS samples by LC-MS/MS with minimal sample preparation.</P>

      • SCISCIESCOPUS

        Effect of annealing of graphene layer on electrical transport and degradation of Au/graphene/n-type silicon Schottky diodes

        Kim, D.J.,Kim, G.S.,Park, N.W.,Lee, W.Y.,Sim, Y.,Kim, K.S.,Seong, M.J.,Koh, J.H.,Hong, C.H.,Lee, S.K. Elsevier Sequoia 2014 JOURNAL OF ALLOYS AND COMPOUNDS Vol.612 No.-

        We have investigated the effect of annealing of graphene sheets on the electrical properties of Au/graphene/n-type silicon Schottky diode. Large scale graphene sheets were grown by chemical vapor deposition and then annealed at 300, 400, and 500<SUP>o</SUP>C; one sheet was left un-annealed as the control. The diodes were fabricated by transferring the graphene sheets directly onto n-type Si substrates and the current-voltage (I-V) and capacitance-voltage (C-V) characteristics were evaluated. The average values of the Schottky barrier height (SBH) and ideality factor (η) for the as-fabricated Au/graphene/n-type silicon Schottky diode from I-V measurements were determined to be ~0.8+/-0.01eV and ~1.79+/-0.05, respectively, whereas the SBH from C-V measurements was ~0.89+/-0.01eV. The electrical transport characteristics measured at room temperature indicated that annealing of graphene sheet prior to the transfer of the graphene onto the n-Si substrates significantly reduces the electric degradation of the Schottky diodes, even though no distinct differences in other electric properties, including ideality factors and SBHs, before or after annealing of the graphene sheets were observed. Thus, by simply annealing the graphene sheets at 500<SUP>o</SUP>C, we found that the Au/graphene/n-type silicon Schottky diode showed an approximately 3.3-fold lower series resistance as compared with the un-annealed Schottky diode under air exposure of up to 7days. These annealed diodes showed significantly reduced electrical degradation by removing the potentially trapped H<SUB>2</SUB>O and/or O<SUB>2</SUB> at the interface between the graphene layer and the n-Si substrate.

      • Age-related differences in virtual histology-intravascular ultrasound findings in patients with coronary artery disease

        Hong, Y.J.,Jeong, M.H.,Choi, Y.H.,Ma, E.H.,Ko, J.S.,Lee, M.G.,Park, K.H.,Sim, D.S.,Yoon, N.S.,Youn, H.J.,Kim, K.H.,Park, H.W.,Kim, J.H.,Ahn, Y.,Cho, J.G.,Park, J.C.,Kang, J.C. Japanese College of Cardiology 2010 Journal of cardiology Vol.55 No.2

        Background: We assessed the age-related differences in pre-intervention virtual histology-intravascular ultrasound (VH-IVUS) findings at target lesion sites in patients with coronary artery disease. Methods: A total of 553 patients who underwent pre-intervention VH-IVUS imaging were grouped according to age: non-elderly (@?70 years, n=429) and elderly (>70 years, n=124); 191 had stable angina and 362 acute coronary syndrome. VH-IVUS classified the tissue into: fibrotic, fibro-fatty, dense calcium (DC), and necrotic core (NC). Results: Overall, the absolute and percent volumes of DC (11.0+/-11.0mm<SUP>3</SUP> vs. 9.7+/-11.9mm<SUP>3</SUP>, P=0.033; 11.7+/-8.1% vs. 9.8+/-7.2%, P=0.014, respectively) and NC (18.5+/-17.6mm<SUP>3</SUP> vs. 16.6+/-18.9mm<SUP>3</SUP>, P=0.020; 18.8+/-8.8% vs. 16.5+/-9.3%, P=0.026, respectively) were significantly greater in the elderly than in the non-elderly. In stable angina patients, the absolute and percent volumes of DC (10.4+/-9.9mm<SUP>3</SUP> vs. 7.2+/-7.6mm<SUP>3</SUP>, P=0.022; 13.4+/-10.0% vs. 9.2+/-6.5%, P=0.011, respectively) and NC (14.8+/-11.2mm<SUP>3</SUP> vs. 12.0+/-11.9mm<SUP>3</SUP>, P=0.035; 19.6+/-8.8% vs. 15.5+/-8.4%, P=0.006, respectively) were significantly greater in the elderly. However, in acute coronary syndrome patients, there were no significant differences in absolute and percent volumes of DC (11.4+/-11.6mm<SUP>3</SUP> vs. 10.9+/-13.4mm<SUP>3</SUP>, P=0.8; 10.7+/-6.5% vs. 10.1+/-7.5%, P=0.5, respectively) and NC (24.1+/-20.3mm<SUP>3</SUP> vs. 23.9+/-21.2mm<SUP>3</SUP>, P=0.9; 22.0+/-8.8% vs. 21.3+/-9.6%, P=0.6, respectively) between the elderly and non-elderly groups. Myocardial infarction (OR: 2.56, 95% CI: 1.45-4.12, P=0.003), diabetes mellitus (OR: 2.23, 95% CI: 1.30-3.53, P=0.009), and high-sensitivity C-reactive protein (OR: 1.44, 95% CI: 1.06-2.45, P=0.042), but not age, were independent predictors of percent NC volume >20% in lesion site. Conclusions: Myocardial infarction, diabetes mellitus, and high-sensitivity C-reactive protein, but not age, were associated with NC-rich lesions. Clinical presentation, risk factors, and inflammatory status, but not age, are important factors for plaque components.

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