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      • Involvement of S6K1 in mitochondria function and structure in HeLa cells

        Park, J.,Tran, Q.,Mun, K.,Masuda, K.,Kwon, S.H.,Kim, S.H.,Kim, D.H.,Thomas, G.,Park, J. Pergamon Press ; Elsevier Science Ltd 2016 Cellular signalling Vol.28 No.12

        The major biological function of mitochondria is to generate cellular energy through oxidative phosphorylation. Apart from cellular respiration, mitochondria also play a key role in signaling processes, including aging and cancer metabolism. It has been shown that S6K1-knockout mice are resistant to obesity due to enhanced beta-oxidation, with an increased number of large mitochondria. Therefore, in this report, the possible involvement of S6K1 in regulating mitochondria dynamics and function has been investigated in stable lenti-shS6K1-HeLa cells. Interestingly, S6K1-stably depleted HeLa cells showed phenotypical changes in mitochondria morphology. This observation was further confirmed by detailed image analysis of mitochondria shape. Corresponding molecular changes were also observed in these cells, such as the induction of mitochondrial fission proteins (Drp1 and Fis1). Oxygen consumption is elevated in S6K1-depeleted HeLa cells and FL5.12 cells. In addition, S6K1 depletion leads to enhancement of ATP production in cytoplasm and mitochondria. However, the relative ratio of mitochondrial ATP to cytoplasmic ATP is actually decreased in lenti-shS6K1-HeLa cells compared to control cells. Lastly, induction of mitophagy was found in lenti-shS6K1-HeLa cells with corresponding changes of mitochondria shape on electron microscope analysis. Taken together, our results indicate that S6K1 is involved in the regulation of mitochondria morphology and function in HeLa cells. This study will provide novel insights into S6K1 function in mitochondria-mediated cellular signaling.

      • Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation

        Kim, S.-H.,Lee, S.-O.,Park, I.-A.,Park, S.J.,Choi, S.-H.,Kim, Y.S.,Woo, J.H.,Park, S.-K.,Park, J.S.,Kim, S.C.,Han, D.J. Blackwell Publishing Inc 2010 Transplant infectious disease Vol.12 No.2

        <P>S.-H. Kim, S.-O. Lee, I.-A. Park, S.J. Park, S.-H. Choi, Y.S. Kim, J.H. Woo, S.-K. Park, J.S. Park, S.C. Kim, D.J. Han. Diagnostic usefulness of a T cell-based assay for latent tuberculosis infection in kidney transplant candidates before transplantation.Transpl Infect Dis 2010: <B>12:</B> 113–119. All rights reserved</P><P>Background</P><P>The presence of latent tuberculosis (TB) infection (LTBI) should be evaluated before kidney transplantation. Although a new T cell-based assay for diagnosing LTBI gave promising results, this assay has not yet been compared with the tuberculin skin test (TST) for diagnosing LTBI in renal transplant candidates before transplantation.</P><P>Patients and methods</P><P>All adult patients admitted to a single institute for renal transplantation over a 1-year period were prospectively enrolled. A clinically predictive risk of LTBI was defined as: (i) recent close contact with a person with pulmonary TB; (ii) abnormal chest radiography; (iii) a history of untreated or inadequately treated TB; or (iv) a new infection (i.e., a recent conversion of TST).</P><P>Results</P><P>Of 209 renal recipients, 47 (22%) had a positive TST≥5 mm, 21 (10%) had a positive TST≥10 mm, 65 (30%) had a positive T-SPOT.<I>TB</I> test, and 25 (12%) had an indeterminate T-SPOT.<I>TB</I> test. The induration size of TST was significantly associated with a high positivity rate on T-SPOT.<I>TB</I> (<I>P</I><0.001). Agreement between T-SPOT.<I>TB</I> test and TST≥10 mm was fair (<I>k</I>=0.24, 95% confidence interval 0.11–0.36). However, neither univariate nor multivariate analysis showed any association between the clinical risk for LTBI and positivity on T-SPOT.<I>TB</I> or TST.</P><P>Conclusion</P><P>T-SPOT.<I>TB</I> test was more frequently positive than TST in renal transplant candidates. However, further longitudinal studies are awaited to determine whether the ability of T-SPOT.<I>TB</I> assay to detect LTBI in renal transplant recipients can better predict the development of TB than can TST after transplantation.</P>

      • SCISCIESCOPUS

        Pulse Shape Discrimination of Nuclear Recoil and Electron Recoil Events With a NaI(Tl) Crystal for Dark Matter Search

        Kim, K. W.,Adhikari, G.,Adhikari, P.,Choi, S.,Ha, C.,Hahn, I. S.,Jeon, E. J.,Joo, H. W.,Kang, W. G.,Kim, H. J.,Kim, N. Y.,Kim, S. K.,Kim, Y. D.,Kim, Y. H.,Lee, H. S.,Lee, M. H.,Leonard, D. S.,Oh, S. Y IEEE 2016 IEEE transactions on nuclear science Vol.63 No.2

        <P>In order to investigate discrimination between nuclear recoil and electron recoil events for the KIMS-NaI dark matter search experiment, we measured the pulse shapes produced by neutrons and gamma rays in a NaI(Tl) crystal. Relatively good pulse shape discrimination (PSD) power due to high light output of recently developed crystals makes it possible to test whether the annual modulation signal observed by the DAMA/LIBRA experiment is caused by nuclear recoil events. We applied the PSD to underground data taken with a 9.15 kg low-background and high-light-output NaI(Tl) crystal for 134 days. Good agreement between underground data and electron recoil events was observed.</P>

      • SCIESCOPUSKCI등재

        Optimal Dietary Ratio of Spray Dried Plasma Protein (SDPP) and Dried Porcine Solubles (DPS) in Improving Growth Performance and Immune Status in Pigs Weaned at 21 Days of Age

        Kim, J.D.,Hyun, Y.,Sohn, K.S.,Kim, T.J.,Woo, H.J.,Han, In K. Asian Australasian Association of Animal Productio 2001 Animal Bioscience Vol.14 No.3

        An experiment was conducted to determine the optimal inclusion ratio of spray dried plasma protein (SDPP) and dried porcine solubles (DPS) for maximizing growth and improving immunity in weaned pigs. One hundred-fifty male (barrow) pigs were allotted in a completely randomized block design. Treatments were as follows: 1) control (6% SDPP), 2) S6D6 (6% SDPP+6% DPS), 3) S6D3 (6% SDPP+3% DPS), 4) S3D6 (3% SDPP+6% DPS) and 5) S3D3 (3% SDPP+3% DPS). Each treatment has 6 replicates with 5 pigs per replicate. Average daily gain (ADG) and average daily feed intake (ADFI) were highest, but not significantly different when pigs were fed a diet contained 6% SDPP and DPS from d 0 to 7 after weaning. Pigs fed the S6D3 diet showed better weight gain and feed intake than other treatments, especially compared with pigs fed S3D6 diet (p<0.05) from d 8 to 21 after weaning. For the overall experimental period, pigs fed the S6D3 diet showed the best improvement in ADG and ADFI. The digestibilities of dry matter (DM) and crude protein (CP) were higher in pigs fed the S6D6 diet than other diets from d 0 to 7 after weaning. However, pigs fed S6D3 diet showed higher DM, CP and essential amino acids (except methionine and arginine) digestibilities than pigs fed other diets from d 8 to 21 after weaning, although there was no significant difference. From d 8 to 21 after weaning, threonine, valine, isoleucine and leucine digestibilites were higher in S6D6 group, and phenyalanine, histidine, lysine and arginine digestibility were higher in S6D3 group than other groups. The ratio of CD4 and CD8 positive lymphocytes during the overall experimental period was independent of the ratio of SDPP and DPS. However, CD4+:CD8+ ratio was numerically lowered in pigs fed diet the S6D3 diet. Therefore, the present study suggests that an optimal inclusion ratio for maximizing growth performance and maintaining low immune status is 6% of SDPP and 3% of DPS in weaned pigs.

      • ZNF509S1 downregulates PUMA by inhibiting p53K382 acetylation and p53-DNA binding

        Jeon, B.N.,Yoon, J.H.,Han, D.,Kim, M.K.,Kim, Y.,Choi, S.H.,Song, J.,Kim, K.S.,Kim, K.,Hur, M.W. Elsevier Science 2017 Biochimica et biophysica acta. Gene regulatory mec Vol.1860 No.9

        Expression of the POK family protein ZNF509L, and -its S1 isoform, is induced by p53 upon exposure to genotoxic stress. Due to alternative splicing of the ZNF509 primary transcript, ZNF509S1 lacks the 6 zinc-fingers and C-terminus of ZNF509L, resulting in only one zinc-finger. ZNF509L and -S1 inhibit cell proliferation by activating p21/CDKN1A and RB transcription, respectively. When cells are exposed to severe DNA damage, p53 activates PUMA (p53-upregulated modulator of apoptosis) transcription. Interestingly, apoptosis due to transcriptional activation of PUMA by p53 is attenuated by ZNF509S1. Thus we investigated the molecular mechanism(s) underlying the transcriptional attenuation and anti-apoptotic effects of ZNF509S1. We show that ZNF509S1 modulation of p53 activity is important in PUMA gene transcription by modulating post-translational modification of p53 by p300. ZNF509S1 directly interacts with p53 and inhibits p300-mediated acetylation of p53 lysine K382, with deacetylation of p53 K382 leading to decreased DNA binding at the p53 response element 1 of the PUMA promoter. ZNF509S1 may play a role not only in cell cycle arrest, by activating RB expression, but also in rescuing cells from apoptotic death by repressing PUMA expression in cells exposed to severe DNA damage.

      • SCIESCOPUS

        An improved data stream algorithm for clustering

        Kim, S.S.,Ahn, H.K. Elsevier 2015 Computational Geometry Vol.48 No.9

        In the k-center problem for streaming points in d-dimensional metric space, input points are given in a data stream and the goal is to find the k smallest congruent balls whose union covers all input points by examining them. In the single-pass streaming model, input points are allowed to be examined only once and the amount of space that can be used to store relative information is limited. In this paper, we present a single-pass, (1.8+ε)-factor, O(d/ε)-space data stream algorithm for the Euclidean 2-center problem for any d≥1. This is the first result with an approximation factor below 2 using O(d/ε) space for any d. Our algorithm naturally extends to the Euclidean k-center problem with k>2. We present a single-pass (1.8+ε)-factor data stream algorithm for the Euclidean k-center problem for any d≥1, which uses O(2<SUP>k</SUP>(k+3)!d/ε) space and O(2<SUP>k</SUP>(k+2)!d/ε) update time.

      • SCISCIESCOPUS

        Phase II study of S-1 combined with oxaliplatin as therapy for patients with metastatic biliary tract cancer: influence of the <i>CYP2A6</i> polymorphism on pharmacokinetics and clinical activity

        Kim, K-p,Jang, G,Hong, Y S,Lim, H-S,Bae, K-s,Kim, H-S,Lee, S S,Shin, J-G,Lee, J-L,Ryu, M-H,Chang, H-M,Kang, Y-K,Kim, T W Nature Publishing Group 2011 The British journal of cancer Vol.104 No.4

        <P><B>Background:</B></P><P>Advanced biliary cancer is often treated with fluoropyrimidine-based chemotherapy. In this study, we evaluated the efficacy and tolerability of a combination of S-1, an oral fluoropyrimidine prodrug, and oxaliplatin in patients with metastatic biliary cancer.</P><P><B>Methods:</B></P><P>Patients with histologically confirmed metastatic biliary cancer and no history of radiotherapy or chemotherapy were enrolled. Oxaliplatin was administered intravenously (130 mg m<SUP>−2</SUP>), followed by 14-day administration of oral S-1 (40 mg m<SUP>−2</SUP> twice daily) with a subsequent 7-day rest period every 21 days. Pharmacokinetic analysis of S-1 was performed at cycle 1. Patients were genotyped for <I>CYP2A6</I> polymorphisms (<SUP>*</SUP>1, <SUP>*</SUP>4, <SUP>*</SUP>7, <SUP>*</SUP>9 or <SUP>*</SUP>10), and pharmacokinetic and clinical parameters compared according to the <I>CYP2A6</I> genotype.</P><P><B>Results:</B></P><P>In total, 49 patients were evaluated, who received a median of four cycles. The overall response rate was 24.5%. Median progression-free and overall survival was 3.7 and 8.7 months, respectively. The most common haematological grade 3 out of 4 toxicity was neutropenia (14%), while non-hematological grade 3 out of 4 toxicities included anorexia (14%), nausea (12%), asthenia (10%), vomiting (10%), and diarrhoea (4%). Biotransformation of S-1 (AUC<SUB>0−24 h</SUB> of 5-fluorouracil/AUC<SUB>0−24 h</SUB> of tegafur) was 1.85-fold higher for the <I>*1/*1</I> group than for the other groups (90% confidence interval 1.37–2.49). Diarrhoea (<I>P</I>=0.0740), neutropenia (<I>P</I>=0.396), and clinical efficacy (response rate, <I>P</I>=0.583; PFS, <I>P</I>=0.916) were not significantly associated with <I>CYP2A6</I> genotype, despite differences in 5-FU exposure.</P><P><B>Conclusion:</B></P><P>The combination of S-1 and oxaliplatin appears to be active and well tolerated in patients with metastatic biliary cancer, and thus is feasible as a therapeutic modality. <I>CYP2A6</I> genotypes are associated with differences in the biotransformation of S-1. However, the impact of the <I>CYP2A6</I> polymorphism on variations in clinical efficacy or toxicity requires further evaluation.</P>

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