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      • Particle distribution in melt-processed Y<sub>1.5</sub> Ba<sub>2</sub>Cu<sub>3</sub>O<sub>x</sub> superconductors with BaCeO<sub>3</sub> addition

        Youn, J.S.,No, K.,Kim, Y.H.,Mahmood, A.,Jun, B.H.,Han, Y.H.,Sung, T.H.,Kim, C.J. North-Holland 2009 Physica. C, Superconductivity Vol.469 No.15

        To understand the effect of BaCeO<SUB>3</SUB> on a Y<SUB>2</SUB>BaCuO<SUB>5</SUB> (Y211) distribution, Y<SUB>1.5</SUB>Ba<SUB>2</SUB>Cu<SUB>3</SUB>O<SUB>x</SUB> (Y1.5) superconductors with/without 1wt.% BaCeO<SUB>3</SUB> additions were prepared by a top-seeded melt-textured growth (TSMG) process. Two different BaCeO<SUB>3</SUB> powders (as-synthesized (coarse powder) and an attrition-milled (fine powder)) were used and the size effect was compared with that obtained from a Y1.5 sample with no addition. A refinement of the Y211 particles was achieved for both the as-synthesized and attrition-milled BaCeO<SUB>3</SUB> additions. The distribution of the Y211 particles was most uniform in the Y1.5 sample prepared with the attrition-milled BaCeO<SUB>3</SUB> powder due to the reduced size of the Y211-free regions by the fine size BaCeO<SUB>3</SUB> addition. The highest J<SUB>c</SUB> was achieved in the Y1.5 sample prepared with the attrition-milled BaCeO<SUB>3</SUB> powder. The J<SUB>c</SUB> result agreed well with the microstructure variations by the addition of BaCeO<SUB>3</SUB> powders.

      • Heat, heat waves, and out-of-hospital cardiac arrest

        Kang, S.H.,Oh, I.Y.,Heo, J.,Lee, H.,Kim, J.,Lim, W.H.,Cho, Y.,Choi, E.K.,Yi, S.M.,Sang, D.S.,Kim, H.,Youn, T.J.,Chae, I.H.,Oh, S. Elsevier/North-Holland Biomedical Press 2016 INTERNATIONAL JOURNAL OF CARDIOLOGY Vol.221 No.-

        <P>Objective: Cardiac arrest is one of the common presentations of cardiovascular disorders and a leading cause of death. There are limited data on the relationship between out-of-hospital cardiac arrest (OHCA) and ambient temperatures, specifically extreme heat. This study investigated how heat and heat waves affect the occurrence of OHCA. Methods: Seven major cities in Korea with more than 1 million residents were included in this study. A heat wave was defined as a daily mean temperature above the 98th percentile of the yearly distribution for at least two consecutive days. Results: A total of 50,318 OHCAs of presumed cardiac origin were identified from the nationwide emergency medical service database between 2006 and 2013. Ambient temperature and OHCA had a J-shaped relationship with a trough at 28 degrees C. Heat waves were shown to be associated with a 14-% increase in the risk of OHCA. Adverse effects were apparent from the beginning of each heat wave period and slightly increased during its continuation. Excess OHCA events during heat waves occurred between 3 PM and 5 PM. Subgroup analysis showed that those 65 years or older were significantly more susceptible to heat waves. Conclusions: Ambient temperature and OHCA had a J-shaped relationship. The risk of OHCA was significantly increased with heat waves. Excess OHCA events primarily occurred during the afternoon when the temperature was high. We found that the elderly were more susceptible to the deleterious effects of heat waves. (C) 2016 Elsevier Ireland Ltd. All rights reserved.</P>

      • Biochemical, pharmaceutical and therapeutic properties of long-acting lithocholic acid derivatized exendin-4 analogs

        Chae, S.Y.,Jin, C.H.,Shin, J.H.,Son, S.,Kim, T.H.,Lee, S.,Youn, Y.S.,Byun, Y.,Lee, M.S.,Lee, K.C. Elsevier Science Publishers 2010 Journal of controlled release Vol.142 No.2

        Alterations in the physicochemical characteristics of peptide drugs can transform their biological and pharmaceutical features. In the present study, we explored the potentials of lithocholic acid (LCA)-modified exendin-4 derivatives as novel long-acting GLP-1 receptor agonists. Exendin-4 was modified with lithocholic acid at two lysine residues to produce three derivatives that were obtained by reverse-phase HPLC separation, namely, Lys<SUP>12</SUP>-LCA-exendin-4 (LCA-M2), Lys<SUP>27</SUP>-LCA-exendin-4 (LCA-M1), and Lys<SUP>12,27</SUP>-LCA-exendin-4 (LCA-Di)). The biological, pharmacological, and physicochemical characteristics of these three exendin-4 analogues were then investigated. Although slight reductions in the GLP-1 receptor binding capacity and insulinotropic activity of exendin-4 were observed after derivatization, the mono-LCA substitutions, especially LCA-M1, well-preserved antidiabetic activity in type 2 diabetic mice when administered subcutaneously or intraperitoneally. Furthermore, the pharmacokinetic characteristics were dramatically enhanced, that is, absorption was delayed and elimination half-life was increased (1.6+/-0.4 and 9.7+/-1.4h by exendin-4 and LCA-M1, respectively). The enhanced long-acting characteristics of the derivative was found to be due to albumin binding and nanoparticle formation, and these were verified by the restoration of normoglycemia in type 2 diabetic mice after single injection (>24h, >10nmol/kg, s.c.) and daily injections (15nmol/kg/day) maintained normoglycemia for the 4-week administration period. Furthermore, antidiabetic potentials, such as, glucose clearance kinetics and percentage areas occupied by pancreatic β-cells were also enhanced by long-term LCA-M1 administration. The present study demonstrates that the derivatization of exendin-4 with LCA offers a possible means of producing a long-acting GLP-1 receptor agonist.

      • SCISCIESCOPUS

        <i>Bacillus</i>‐derived poly‐γ‐glutamic acid attenuates allergic airway inflammation through a Toll‐like receptor‐4‐dependent pathway in a murine model of asthma

        Lee, K.,Kim, S.,H.,Yoon, H. J.,Paik, D. J.,Kim, J. M.,Youn, J. Blackwell Publishing Ltd 2011 Clinical and experimental allergy Vol.41 No.8

        <P><B>Summary</B></P><P><B>Background </B> Asthma is an inflammatory disease of the airways that is mediated by Th2 responses. Poly‐γ‐glutamic acid (γ‐PGA) is an extracellular polymeric compound that is synthesized by <I>Bacillus</I> cells. Previously, we found that γ‐PGA promoted Th1 cell development in a manner dependent on antigen‐presenting cells, but inhibited Th2 cell development.</P><P><B>Objective </B> To investigate the effect of γ‐PGA on dendritic cells (DCs), and its potential for treating Th2‐mediated allergic asthma.</P><P><B>Methods </B> Wild‐type, Toll‐like receptor (TLR)‐2 deficient, and TLR‐4‐defective mice were used. DCs derived from the bone marrow and extracted from the lung were stimulated with γ‐PGA and assayed for the expression of signalling molecules, costimulatory molecules, and cytokines. Mice were sensitized and challenged with ovalbumin (OVA) to induce asthma. They were repeatedly injected intranasally with γ‐PGA before and during the challenge period, and inflammation and structural remodelling of the airways were examined.</P><P><B>Results </B> γ‐PGA selectively signalled conventional DCs to activate NF‐κB and mitogen‐activated protein kinase, leading to the up‐regulation of CD86, CD40, and IL‐12, but not IL‐10 and IL‐6. These effects of γ‐PGA were dependent on TLR‐4 and independent of TLR‐2. Importantly, the intranasal administration of γ‐PGA to OVA‐sensitized/challenged mice reduced the airway hyperresponsiveness and allergic inflammation such as leucocyte influx, goblet cell hyperplasia, eosinophilia, and Th2 cytokine production. In addition to lowered IgE titres, the treatment of mice with γ‐PGA significantly reduced the multiplication and Th2 polarization of mediastinal lymph node T cells upon allergen‐specific restimulation. These anti‐asthmatic effects of γ‐PGA were also abolished in TLR‐4‐defective mice.</P><P><B>Conclusions and Clinical Relevance </B> Our data indicate that γ‐PGA activates DCs to favour Th1 cell induction through a TLR‐4‐dependent pathway and alleviates pathologic symptoms in a Th2‐biased asthmatic model. These findings highlight the potential of γ‐PGA for the treatment of asthma and other allergic disease in which Th2 polarization plays an important role.</P><P> <I>Cite this as</I>: K. Lee, S.‐H. Kim, H. J. Yoon, D. J. Paik, J. M. Kim and J. Youn, <I>Clinical & Experimental Allergy</I>, 2011 (41) 1143–1156.</P>

      • An emerging recombinant cluster of nephropathogenic strains of avian infectious bronchitis virus in Korea

        Lim, T.H.,Lee, H.J.,Lee, D.H.,Lee, Y.N.,Park, J.K.,Youn, H.N.,Kim, M.S.,Lee, J.B.,Park, S.Y.,Choi, I.S.,Song, C.S. Elsevier Science 2011 Infection, genetics and evolution Vol.11 No.3

        The infectious bronchitis virus (IBV) is continuously evolving through point mutation and recombination of their genome, subsequently the emergence of IBV variants complicates disease control. The objective of this study was to investigate genetic characterization of new IBV variants isolated from commercial chicken flocks in Korea collected between 2005 and 2010. Phylogenetic analysis revealed that all new IBV isolates belonged to Korean group II (K-II), which included the nephropathogenic IBV strains. However, the isolates formed a new gene cluster that was distinguished from the two distinct K-II subgroups (KM91-like and QX-like). Recombination events were identified in the S1 gene, with their putative parental strains being the KM91-like or QX-like subgroup. In addition, two crossover sites were observed in the S1 gene of IBV isolates. These results suggest that natural genetic recombination between heterologous strains classified into different genetic groups has occurred and may have caused the emergence of new IBV strains. This finding provides important information on IBV evolution and is essential for the effective control of IB in Korea.

      • Effect of oxygen partial pressure on the morphology and properties of Ce doped YBCO films fabricated by a MOCVD process

        Kim, Y.H.,Kim, C.J.,Jun, B.H.,Sung, T.H.,Han, Y.H.,Han, S.C.,Paik, H.J.,Youn, J.S.,No, K. North-Holland 2009 Physica. C, Superconductivity Vol.469 No.15

        Rare-earth (RE) (e.g. Sm, Dy, Ce, etc.) doping has been widely investigated to improve critical current density (J<SUB>c</SUB>) of YBa<SUB>2</SUB>Cu<SUB>3</SUB>O<SUB>7-X</SUB> (YBCO) coated conductors (CC). Oxygen partial pressure is known to be a key parameter in terms of affecting the J<SUB>c</SUB> of YBCO films. In this work, the effect of oxygen partial pressure on the microstructure and J<SUB>c</SUB> of a Ce doped YBCO film was examined. Ce doped YBCO films were deposited on (100) SrTiO<SUB>3</SUB> (STO) single crystal substrates at oxygen partial pressures of 2.5, 5.0, and 10.0Torr using a metal organic chemical vapor deposition (MOCVD) method. Due to the enhanced migration of surface adatoms under reduced oxygen partial pressure, a 1wt% Ce doped YBCO film had a stoichiometric, dense surface. In addition, the zero-field J<SUB>c</SUB> (at 77K) of the 1wt% Ce doped YBCO film deposited at reduced oxygen partial pressure was increased. Irrespective of the amount of Ce, the Ce doped YBCO film showed an increased zero-field J<SUB>c</SUB> (at 77K) under reduced oxygen partial pressure.

      • SCISCIESCOPUS

        CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11<sup>p110</sup>

        Choi, H-H,Choi, H-K,Jung, S Y,Hyle, J,Kim, B-J,Yoon, K,Cho, E-J,Youn, H-D,Lahti, J M,Qin, J,Kim, S-T Macmillan Publishers Limited 2014 Oncogene Vol.33 No.1

        Checkpoint kinase 2 (CHK2) kinase is a key mediator in many cellular responses to genotoxic stresses, including ionizing radiation (IR) and topoisomerase inhibitors. Upon IR, CHK2 is activated by ataxia telangiectasia mutated kinase and regulates the S-phase and G1-S checkpoints, apoptosis and DNA repair by phosphorylating downstream target proteins, such as p53 and Brca1. In addition, CHK2 is thought to be a multi-organ cancer susceptibility gene. In this study, we used a tandem affinity purification strategy to identify proteins that interact with CHK2 kinase. Cyclin-dependent kinase 11 (CDK11)<SUP>p110</SUP> kinase, implicated in pre-mRNA splicing and transcription, was identified as a CHK2-interacting protein. CHK2 kinase phosphorylated CDK11<SUP>p110</SUP> on serine 737 in vitro. Unexpectedly, CHK2 kinase constitutively phosphorylated CDK11<SUP>p110</SUP> in a DNA damage-independent manner. At a molecular level, CDK11<SUP>p110</SUP> phosphorylation was required for homodimerization without affecting its kinase activity. Overexpression of CHK2 promoted pre-mRNA splicing. Conversely, CHK2 depletion decreased endogenous splicing activity. Mutation of the phosphorylation site in CDK11<SUP>p110</SUP> to alanine abrogated its splicing-activating activity. These results provide the first evidence that CHK2 kinase promotes pre-mRNA splicing via phosphorylating CDK11<SUP>p110</SUP>.

      • KCI등재

        중소기업을 위한 교육훈련이 고객만족과 행동의도에 미치는 영향에 관한 연구

        구자활(J.H. Koo),김영형(Y.H. Kim),오현승(H.S. Oh),이세재(Lee ㆍK.S),윤광식(K.S. Youn),조진형(J.H. Cho) 한국산업경영시스템학회 2010 한국산업경영시스템학회지 Vol.33 No.1

        Technological innovation depends on the quality of workers, whose ability is the key component to raise business competitiveness. Our study evaluates how satisfactory is the training of workers at small and medium sized firms , and suggest how to improve upon it. We show the theoretical framework for the relation between customer satisfaction and their behavioral intent on the one side, and factors of training service quality. Our result show: (I) Factors affecting customer satisfaction are, in descending order of importance, expertise, policy, follow-up service, attitude and behavior, and convenience. (2) Contrary to established views on the service quality, satisfaction for training would not be the prerequisite variable for intent to act, in case of training service quality. (3) Satisfaction level for training depends on the type of organization in charge of training (government, university, or private sector.) lt also varied among different types of business (L-type, A-type, and J-type.) Small and medium sized firms find it difficult to commit to training education due to lack of money and manpower. The recent expansion of free training service would address part of this problem. On the other hand, the outfit in charge of training could boost service quality by customizing their training program to the type of business they cater to

      • SCISCIESCOPUS

        von Hippel–Lindau protein promotes Skp2 destabilization on DNA damage

        Roe, J-S,Kim, H-R,Hwang, I-Y,Cho, E-J,Youn, H-D Macmillan Publishers Limited 2011 Oncogene Vol.30 No.28

        Germline mutations in the von Hippel–Lindau (VHL) tumor suppressor gene cause VHL disease, a rare and autosomal-dominant genetic syndrome. Because VHL protein (pVHL) is the master regulator of hypoxia-inducible factor alpha (HIFα), the most prominent feature of VHL disease is the deregulation of HIFα proteins. However, the precise mechanism by which the loss of pVHL function contributes to tumorigenesis is not fully understood. Here, we show that pVHL destabilizes the F-box protein Skp2, a chief component of Skp, Cullin, F-box-containing complex that promotes DNA synthesis in the S phase. The β-domain of pVHL interacts with Skp2, stimulating proteasome-dependent Skp2 degradation, but the destabilization of Skp2 does not depend on the E3 ubiquitin ligase activity of pVHL. Notably, the generation of DNA damage induces Skp2 degradation, which is attenuated by the suppression of endogenous pVHL expression. One possible mechanism of pVHL-dependent Skp2 degradation entails the antagonizing of Akt-mediated Skp2 phosphorylation, which maintains Skp2 stability. Reintroduction of VHL into VHL-null renal cell carcinoma (RCC) cells decreased Skp2 levels and restored DNA damage-dependent Skp2 degradation. These results identify the tumor suppressor function of pVHL in delaying the S-phase progression to inhibit cell proliferation on DNA damage. Clinically, this report explains as to why Skp2 accumulates abnormally in RCC tissues.

      • Azide-based heterobifunctional poly(ethylene oxide)s: NaN3-initiated 'living' polymerization of ethylene oxide and chain end functionalizations

        Yang, S.,Kim, Y.,Kim, H.,Siddique, A.,Youn, G.,Kim, H.,Park, H.,Lee, J.,Kim, S.,Kim, J. Royal Society of Chemistry 2016 Polymer chemistry Vol.7 No.2

        <P>In this study, sodium azide (NaN3) was employed as a functional anionic initiator to polymerize ethylene oxide in N, N-dimethylformamide (DMF) leading to the production of the reactive polymeric alkoxide. The molecular weights of all products were controlled within the 2800-10 000 g mol(-1) range on the basis of the stoichiometric balance. NaN3-initiated polymerization of ethylene oxide (EO) and chain end functionalization of the resulting alkoxide were found to be a simple and efficient method for synthesizing heterobifunctional PEOs. The reaction route via chain end tosylation of a-azide PEOs was found to yield almost quantitative functionalizations for the synthesis of alpha-azide-omega-tosyl PEO, alpha-azide-omega-thiol PEO, and alpha-amine-omega-thiol PEO (over 98 mol%).</P>

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