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        A genetic variation in microRNA target site of <i>KRT81</i> gene is associated with survival in early-stage non-small-cell lung cancer

        Lee, S. Y.,Choi, J. E.,Jeon, H. S.,Hong, M. J.,Choi, Y. Y.,Kang, H. G.,Yoo, S. S.,Lee, E. B.,Jeong, J. Y.,Lee, W. K.,Lee, J.,Cha, S. I.,Kim, C. H.,Kim, Y. T.,Jheon, S.,Son, J. W.,Park, J. Y. Oxford University Press 2015 ANNALS OF ONCOLOGY Vol.26 No.6

        <P>In this study, <I>KRT81</I> rs3660G>C was associated with survival of patients with NSCLC after surgical resection. Mechanistic study suggested that the G-to-C change caused reduced binding efficiency of miRNA, leading to decreased translational repression, thereby increased <I>KRT81</I> expression. The <I>KRT81</I> rs3660G>C may be a useful prognostic biomarker in early-stage NSCLC patients.</P><P><B>Background</B></P><P>MicroRNAs (miRNAs) have a key role in carcinogenesis through negative regulation of their target genes. Therefore, genetic variations in miRNAs or their target sites may affect miRNA–mRNA interactions, thereby result in altered expression of target genes. This study was conducted to investigate the associations between single-nucleotide polymorphisms (SNP) located in the miRNA target sites (poly-miRTSs) and survival of patients with early-stage non-small-cell lung cancer (NSCLC).</P><P><B>Methods</B></P><P>Using public SNP database and miRNA target sites prediction program, 354 poly-miRTSs were selected for genotyping. Among these, 154 SNPs applicable to Sequenom's MassARRAY platform were investigated in 357 patients. A replication study was carried out on an independent patient population (<I>n</I> = 479). <I>Renilla</I> luciferase assay and reverse transcription-polymerase chain reaction were conducted to examine functional relevance of potentially functional poly-miRTSs.</P><P><B>Results</B></P><P>Of the 154 SNPs analyzed in a discovery set, 14 SNPs were significantly associated with survival outcomes. Among these, <I>KRT81</I> rs3660G>C was found to be associated with survival outcomes in the validation cohort. In the combined analysis, patients with the rs3660 GC + CC genotype had a significantly better overall survival compared with those with GG genotype [adjusted hazard ratio (aHR) for OS, 0.65; 95% confidence interval (CI) 0.50–0.85; <I>P</I> = 0.001]. An increased expression of the reporter gene for the C allele of rs3660 compared with the G allele was observed by luciferase assay. Consistently, the C allele was associated with higher relative expression level of <I>KRT81</I> in tumor tissues.</P><P><B>Conclusion</B></P><P>The rs3660G>C affects KRT81 expression and thus influences survival in early-stage NSCLC. The analysis of the rs3660G>C polymorphism may be useful to identify patients at high risk of a poor disease outcome.</P>

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        Full-length genomic analysis of porcine G9P[23] and G9P[7] rotavirus strains isolated from pigs with diarrhea in South Korea

        Kim, H.H.,Matthijnssens, J.,Kim, H.J.,Kwon, H.J.,Park, J.G.,Son, K.Y.,Ryu, E.H.,Kim, D.S.,Lee, W.S.,Kang, M.I.,Yang, D.K.,Hyun, B.H.,Park, S.I.,Park, S.J.,Cho, K.O. Elsevier Science 2012 INFECTION GENETICS AND EVOLUTION Vol.12 No.7

        Group A rotaviruses (RVAs) are agents causing severe gastroenteritis in infants and young animals. G9 RVA strains are believed to have originated from pigs. However, this genotype has emerged as the fifth major human RVA genotype worldwide. To better understand the relationship between human and porcine RVA strains, complete RVA genome data are needed. For human RVA strains, the number of complete genome data have grown exponentially. However, there is still a lack of complete genome data on porcine RVA strains. Recently, G9 RVA strains have been identified as the third most important genotype in diarrheic pigs in South Korea in combinations with P[7] and P[23]. This study is the first report on complete genome analyses of 1 G9P[7] and 3 G9P[23] porcine RVA strains, resulting in the following genotype constellation: G9-P[7]/P[23]-I5-R1-C1-M1-A8-N1-T1-E1-H1. By comparisons of these genotype constellations, it was revealed that the Korean G9P[7] and G9P[23] RVA strains possessed a typical porcine RVA backbone, similar to other known porcine RVA strains. However, detailed phylogenetic analyses revealed the presence of intra-genotype reassortments among porcine RVA strains in South Korea. Thus, our data provide genetic information of G9 RVA strains increasingly detected in both humans and pigs, and will help to establish the role of pigs as a source or reservoir for novel human RVA strains.

      • SCIESCOPUS

        Pinoresinol-4,4'-di-O-β-d-glucoside from Valeriana officinalis root stimulates calcium mobilization and chemotactic migration of mouse embryo fibroblasts

        Do, K.H.,Choi, Y.W.,Kim, E.K.,Yun, S.J.,Kim, M.S.,Lee, S.Y.,Ha, J.M.,Kim, J.H.,Kim, C.D.,Son, B.G.,Kang, J.S.,Khan, I.A.,Bae, S.S. G. Fischer 2009 Phytomedicine Vol.16 No.6

        Lignans are major constituents of plant extracts and have important pharmacological effects on mammalian cells. Here we showed that pinoresinol-4,4'-di-O-β-d-glucoside (PDG) from Valeriana officinalis induced calcium mobilization and cell migration through the activation of lysophosphatidic acid (LPA) receptor subtypes. Stimulation of mouse embryo fibroblast (MEF) cells with 10μM PDG resulted in strong stimulation of MEF cell migration and the EC<SUB>50</SUB> was about 2μM. Pretreatment with pertussis toxin (PTX), an inhibitor of G<SUB>i</SUB> protein, completely blocked PDG-induced cell migration demonstrating that PDG evokes MEF cell migration through the activation of the G<SUB>i</SUB>-coupled receptor. Furthermore, pretreatment of MEF cells with Ki16425 (10μM), which is a selective antagonist for LPA<SUB>1</SUB> and LPA<SUB>3</SUB> receptors, completely blocked PDG-induced cell migration. Likewise, PDG strongly induced calcium mobilization, which was also blocked by Ki16425 in a dose-dependent manner. Prior occupation of the LPA receptor with LPA itself completely blocked PDG-induced calcium mobilization. Finally, PDG-induced MEF cell migration was attenuated by pretreatment with a phosphatidylinositol 3-kinase (PI3K) inhibitor such as LY294002. Cells lacking downstream mediator of PI3K such as Akt1 and Akt2 (DKO cells) showed loss of PDG-induced migration. Re-expression of Akt1 (but not Akt2) completely restored PDG-induced DKO cell migration. Given these results, we conclude that PDG is a strong inducer of cell migration. We suggest that the pharmacological action of PDG may occur through the activation of an LPA receptor whereby activation of PI3K/Akt signaling pathway mediates PDG-induced MEF cell migration.

      • Dual-end-functionalized tin (Sn)-phyllosilicates for the esterification of oleic acid

        Nam, B.,Lee, H.U.,Park, S.Y.,Son, B.C.,Lee, G.W.,Park, J.Y.,Lee, Y.C. Korean Society of Industrial and Engineering Chemi 2016 Journal of industrial and engineering chemistry Vol.41 No.-

        <P>We designed dual-end-functionalized tin (Sn)-phyllosilicate, where the -SH functional groups were subsequently oxidized for -SO3H/SO4H functionalities in a Bronsted acid with/without NH2 functional groups in a Bronsted base. Dual-end-functionalized tin (Sn)-phyllosilicates [MTES:APTS = 1.0:0.11, MTES:TEOS = 1.0:0.11 and 1.0:0.43, v/v] were fabricated where the inorganic framework of Sn species can function as a Lewis acid. The Sn-phyllosilicates with dual acids were applied to esterify oleic acid and produce oleic acid-methyl-ester to test their feasibility as fatty-acid-conversion solid catalysts. In the absence of amine groups, the increase in ratio of tetraethyl orthosilicate (TEOS) to (3-mercaptopropyl)-trimethoxysilane (MTES) for the synthesis of Sn-phyllosilicates (MTES:TEOS = 1.0:0.11 and 1.0:0.43, v/v) increased the recovery of Sn-phyllosilicate in the solvent media and gradually decreased the oleic acid methyl-ester production efficiency (%) of the oleic acid conversion. At the fixed 2.0 wt% Sn-phyllosilicate (MTES:APTS = 1.0:0.11, v/v) loading and oleic acid:MeOH weight ratio = 1:1, an 80 degrees C reaction temperature and 4 h reaction time were determined to be the optimal conditions for the oleic acid methyl-ester production, which had 90% oleic acid conversion efficiency. When the Sn-phyllosilicate (MTES:APTS = 1.0:0.11, v/v) loading was increased from 0.1 to 5.0 wt% at 80 degrees C and 4 h, the fatty-acid conversion efficiency (%) of oleic acid gradually increased from 39.16 to 92.23%. In contrast, Sn-phyllosilicate (MTES:TEOS = 1.0:0.43) had the lowest oleic acid conversion efficiency (%) but the highest catalyst recovery. In summary, this study presents a facile method to produce oleic acid conversion catalysts on an industrial scale. (C) 2016 The Korean Society of Industrial and Engineering Chemistry. Published by Elsevier B.V. All rights reserved.</P>

      • KCI등재

        검정종료돈의 체중변화에 따른 일당중체량, 등지방두께 및 정육율의 반복력과 상관

        김현철,김병우,송광림,오하식,손창준,하동우,이정규 한국동물자원과학회 2002 한국축산학회지 Vol.44 No.5

        본 연구는 1999년 8월부터 2000년 2월까지 공인 제2종돈능력검정소에서 검정 종료된 Duroc종, Landrace종 및 Yorkshire종에 대하여 체중, 등지방두께, 일당증체량 및 정육율을 측정하여, 동일 개체의 반복측정치 간의 반복력과, 상관 및 순위상관을 추정하였으며, 그 결과를 요약하면 다음과 같다. 1. 평균능력은 측정시 체중이 각각 91.0, 114.7, 123.2㎏이였으며, 측정시 일령은 각각 142.1, 173.7, 182.5일이였으며, 정육율은 각각 57.9, 56.2 55.2%였으며, 등지방두께는 각각 1.33, 1.61, 1.63㎝였으며, 일당증체량은 각각 946.6, 879.2, 879.4g으로 나타났다. 2. 각 형질의 측정차수간 상관은 정육율의 경우, 1차와 2차, 1차와 3차, 2차와 3차간 각각 0.493, 0.471, 0.619로 나타났고, 등지방두께의 경우, 각각 0.424, 0.424, 0.700으로 나타났으며, 일당증체량의 경우, 각각 0.716, 0.601, 0.861로 모든 형질에서 1차와 2차간, 1차와 3차간 보다는 2차와 3차간에 높게 추정되었다. 3. 각 측정차수의 형질간 상관은 1차 측정의 경우, 정육율과 등지방두께, 정육율과 일당증체량, 등지방두께와 일당증체량이 각각 -0.597, -0.291, 0.303으로 나타났고, 2차 측정의 경우, 각각 -0.667, -0.292, 0.396으로 나타났으며, 3차 측정의 경우, 각각 -0.711, -0.369, 0.409로 정육율과 등지방두께 및 일당증체량은 부의 상관관계에 있으며, 등지방두께와 일당증체량은 정의 상관관계에 있고, 일령이 증가할수록 상관이 높게 추정되었다. 4. 각 형질의 반복력 추정치를 살펴보면, 등지방두께가 0.374, 정육율이 0.428, 일당증체량이 0.673으로 추정되었으며, 일당증체량의 반복력은 상당히 높게 추정되어, 110㎏까지 검정의 필요성이 인정되지 않으나, 등지방두께와 정육율의 추정치는 낮게 추정되어 더욱 많은 연구가 필요할 것으로 사료된다. The respeatability, correlation and rank correlation coefficients among average daily gain, backfat thickness and lean percent were estimated on the basis of records tested from August 1999 to February 2000 with 695 pigs of Duroc, Landrace and Yorkshire boars and gilts tested at 2nd Korea Swine Test Station located in Ha-dong, Kyeongnam Province. The effect of the sex, breed and month of measured were estimated by the least square method. The repeatabilities were estimated from the component of variance among repeated measurements of the trait for the same animal. The results obtained are summarized as follow ; 1. The means of the major economic traits studied were 142.1 days, 173.7 days and 182.5 days for age at 1st, 2nd and 3rd measure, 57.9%, 56.2% and 55.2% for lean percent at 1st. 2nd and 3rd mesure, 1.33㎝, 1.61㎝ and 1.63㎝ for backfat thickness at 1st. 2nd and 3rd measure, 946.6g, 879.2g and 879.4g for average daily gain at 1st. 2nd and 3rd measure, respectively. 2. The correlation coefficients between the backfat thickness measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.424, 0.700 and 1.424, respectively. The correlation coefficients between the lean percent measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.493, 0.619 and 0.471, respectively. The correlation coefficients between the average daily gain measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.716, 0.861 and 0.601, respectively. 3. The rank correlation coefficients between backfat thickness measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.438, 0.693 and 0.441, respectively. The rank correlation coefficients between lean percent measured at1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.508, 0.593 and 0.478, respectively. The rank correlation coefficients between average daily gain measured at 1st and 2nd, at 2nd and 3rd, at 1st and 3rd were 0.704, 0.834 and 0.571, respectively. 4. The estimated repeatabilities of the traits studied were 0.428 for the lean percent, 0.374 for the backfat thickness and 0.673 for the average daily gain, respectively.

      • 약(葯)배양 기법 이용한 이탈리안 라이그라스 식물체 생산

        김기용,강경민,최기준,임용우,장요순,성병렬,손대영,이병현,조진기 Plant molecular biology and biotechnology research 2002 Plant molecular biology and biotechnology research Vol.2002 No.-

        We obtained regenerated Italian ryegrass (Lolium multiflorum Lam.) plants by anther culture. When Italian ryegrass anther was incubated for 20 days on callus induction medium, MS medium containing 30 g/ℓ of NAA and 1 mg/ℓ of kinetin its callus was induced. The ratio of callus induction was 9.2 %, the mean of callus weight was 8.6 mg/callus/anther. When Italian ryegrass callus was incubated for 50 days on plant regeneration medium, MS medium containing 30 g/ℓ of sucrose, 1 mg/ℓ of NAA and 2 mg/ℓ of kinetin, Italian ryegrass plant was regenerated. The ratio of plant regeneration was 26%.

      • SCISCIESCOPUS

        The novel anthraquinone derivative IMP1338 induces death of human cancer cells by p53-independent S and G2/M cell cycle arrest

        Choi, H.K.,Ryu, H.,Son, A.r.,Seo, B.,Hwang, S.G.,Song, J.Y.,Ahn, J. Masson Pub. USA, Inc 2016 BIOMEDICINE AND PHARMACOTHERAPY Vol.79 No.-

        <P>To identify novel small molecules that induce selective cancer cell death, we screened a chemical library containing 1040 compounds in HT29 colon cancer and CCD18-Co normal colon cells, using a phenotypic cell-based viability assay system with the Cell Counting Kit-8 (CCK-8). We discovered a novel anthraquinone derivative, N-(4-[{(9,10-dioxo-9,10-dihydro-1-anthracenyl)sulfonyl}amino]phenyl)-N-methylacetamide (IMP1338), which was cytotoxic against the human colon cancer cells tested. The MTT cell viability assay showed that treatment with IMP1338 selectively inhibited HCT116, HCT116 p53 (/) , HT29, and A549 cancer cell proliferation compared to that of Beas2B normal epithelial cells. To elucidate the cellular mechanism underlying the cytotoxicity of IMP1338, we examined the effect of IMP1338 on the cell cycle distribution and death of cancer cells. IMP1338 treatment significantly arrested the cell cycle at S and G2/M phases by DNA damage and led to apoptotic cell death, which was determined using FACS analysis with Annexin V/PI double staining. Furthermore, IMP1338 increased caspase-3 cleavage in wild-type p53, p53 knockout HCT116, and HT29 cells as determined using immunoblotting. In addition, IMP1338 markedly induced the phosphorylation of histone H2AX and Chk1 in both cell lines while the combination of 5-fluorouracil (5-FU) and radiation inhibited the viability of HCT116, HCT116 p53 / , and HT29 cells compared to 5-FU or radiation alone. Our findings indicated that IMP1338 induced p53-independent cell death through S and G2/M phase arrest as well as DNA damage. These results provide a basis for future investigations assessing the promising anticancer properties of IMP1338. (C) 2016 Elsevier Masson SAS. All rights reserved.</P>

      • SCISCIESCOPUS

        Genetic diversity of the VP7, VP4 and VP6 genes of Korean porcine group C rotaviruses

        Jeong, Y.J.,Matthijnssens, J.,Kim, D.S.,Kim, J.Y.,Alfajaro, M.M.,Park, J.G.,Hosmillo, M.,Son, K.Y.,Soliman, M.,Baek, Y.B.,Kwon, J.,Choi, J.S.,Kang, M.I.,Cho, K.O. Elsevier Scientific Pub. Co 2015 Veterinary microbiology Vol.176 No.1

        Porcine group C rotaviruses (RVCs) are considered important pathogens due to their economic impact on pig industry and may also cross the host species barrier toward humans. Unlike RVA, however, genetic and phylogenetic data on RVCs from pigs and other host species are scarce. In the present study, full-length ORF sequences of 26 VP7, 9 VP4 and 9 VP6 genes of Korean porcine RVC strains were compared with those of other known RVC strains by phylogenetic analyses and pairwise identity frequency graphs. Applying the established 85% nucleotide identity cut-off value for RVC VP7 classification, the 26 Korean porcine RVC strains belonged to the G1, G3, G6 and G7 genotypes. Although more complete RVC VP4 sequences are warranted before a definitive cut-off value could be determined, a provisional 83% nucleotide cut-off value proposed for RVC VP4 classification resulted in 7 P-genotypes, 5 of which possessed porcine RVC strains. A 90% nucleotide cut-off value for VP6 divided RVC strains into 7 I-genotypes, 5 of which had porcine RVC strains. G/P/I-genotype comparisons suggested the occurrence of rather frequent reassortment events among Korean porcine RVC strains, and strong geographical differences in the distribution of RVC G-genotypes worldwide. Our data indicate that a large genetic diversity exists among porcine RVC strains. For the final genotype determination of each gene segment, more intensified epidemiological studies on animal and human RVC strains throughout the world are needed.

      • SCOPUSKCI등재

        인슐린 치료후 발생한 인슐린 항체에 의한 저혈당증 2예

        김경아,이관우,김미림,김여주,장재남,배성권,손병관 대한내분비학회 1996 Endocrinology and metabolism Vol.11 No.2

        Hirata et al. first described the association of insulin antibodies with hypoglycemia attacks and decreased glucose tolerance in a patient who had not previously received insulin injections. Since that time there have been additional reports in the Japanese literature. Insulin antibodies are present in most of the patients who received insulin for a period of time, usually exceeding six weeks. There were several reports of hypoglycemia in patients with non-insulin-dependent diabetes mellitus who had developed insulin antibody after insulin administration and also in patients with insulin dependent diabetes mellitus. It is well known that either insulin antibody to the lower affinity site or insulin receptor antibody can be a cause of hypoglycemia. Recently, we experienced two cases of hypoglycemia in patient with insulin dependent diabetes mellitus and non- insulin- dependent diabetes mellitus who had developed insulin antibody after insulin administration. Hereby we present these cases with review of the literature(1 Kor Soc Endocrinol 11:240 ~246, 1996).

      • 화염 진단 시스템 설계를 위한 기초 연구 (I)

        박기배,이상호,김종원,진경태,손재익 경북대학교 센서기술연구소 1995 센서技術學術大會論文集 Vol.6 No.1

        The objective of the project was the development of an optical approach which would indicate the presence of a flame and detect deviations from a desired set point. In this work, the flame quality indicator consisted of photodiode, optical fiber, interference filter and data acquisition system, and was tested in a lab-scale methane combustion system. It was needed to apply this system to pilot scale combustor in order to confirm whether temporal fluctuations might be correlated with important parameters of combustion process, such as fuel to air ratio and NO_(x) emissions or not.

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