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Anti-Proliferative Activity of OD78 Is Mediated through Cell Cycle Progression by Upregulation p27kip1 in Rat Aortic Vascular Smooth Muscle Cells

  • Tudev, Munkhtsetseg;Lim, Yong;Park, Eun-Seok;Kim, Won-Sik;Lim, Il-Ho;Kwak, Jae-Hwan;Jung, Jae-Kyung;Hong, Jin-Tae;Yoo, Hwan-Soo;Lee, Mi-Yea;Pyo, Myoung-Yun;Yun, Yeo-Pyo
    • Biomolecules & Therapeutics
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    • v.19 no.2
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    • pp.187-194
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    • 2011
  • Atherosclerosis and post-angiography restenosis are associated with intimal thickening and concomitant vascular smooth muscle cell (VSMC) proliferation. Obovatol, a major biphenolic component isolated from the Magnolia obovata leaf, is known to have anti-inflammatory and anti-tumor activities. The goal of the present study was to enhance the inhibitory effects of obovatol to improve its potential as a preventive or therapeutic agent in atherosclerosis and restenosis. Platelet-derived growth factor (PDGF)-BB-induced proliferation of rat aortic smooth muscle cells (RASMCs) was examined in the presence or absence of a newly synthesized obovatol derivative, OD78. The observed anti-proliferative effect of OD78 was further investigated by cell counting and [$^3H$]-thymidine incorporation assays. Treatment with 1-4 ${\mu}M$ OD78 dose-dependently inhibited the proliferation and DNA synthesis of 25 ng/ml PDGF-BB-stimulated RASMCs. Accordingly, OD78 blocked PDGF-BB-induced progression from the $G_0/G_1$ to S phase of the cell cycle in synchronized cells. OD78 decreased the expression levels of CDK4, cyclin E, and cyclin D1 proteins, as well as the phosphorylation of retinoblastoma protein and proliferating cell nuclear antigen; however, it did not change the CDK2 expression level. In addition, OD78 inhibited downregulation of the cyclin-dependent kinase inhibitor (CKI) $p27^{kip1}$. However, OD78 did not affect the CKI $p21^{cip1}$ or phosphorylation of early PDGF signaling pathway. These results suggest that OD78 may inhibit PDGF-BB-induced RASMC proliferation by perturbing cell cycle progression, potentially through $p27^{kip1}$ pathway activation. Consequently, OD78 may be developed as a potential anti-proliferative agent for the treatment of atherosclerosis and angioplasty restenosis.

Mineralogical Characteristics of Calcite observed in the KAERI Underground Research Tunnel (고준위폐기물 지하처분연구시설(KURT)에서 관찰되는 방해석의 광물학적 특징)

  • Lee, Seung-Yeop;Baik, Min-Hoon;Cho, Won-Jin
    • Journal of the Mineralogical Society of Korea
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    • v.19 no.4 s.50
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    • pp.239-246
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    • 2006
  • KAERI Underground Research Tunnel (KURT) was recently constructed through the site investigation from the yea. of 2003 at KAERI site, Dukjin-dong, Yuseong-gu, Daejeon city. The geo-logic setting of the site has been slightly metamorphosed. There are small fractures developed in the rock and several kinds of secondary filling minerals exist in the fractures. We examined mineralogical characteristics of fracture-filling calcite, which is not only largely distributed, but also can significantly affect the radionuclides migration. The calcite is found along fractures like other secondary minerals, forming thick veins in part. Most calcite-filled fractures contain quartz, iron oxides, and dolomite as minor minerals. The calcite crystals show an characteristic appearance with an uniformly oriented growth, coated with goethite on the edge and the etch-pit sites of their surface. Some calcite crystals have been newly formed by the precipitation of elements dissolved from the tunnel shotcrete wall, and their morphology changed according to the chemistry and flow of groundwater. The calcite can modify the groundwater chemistry and significantly affect the sorption behavior of radionuclides. The characteristic crystal structure and surface morphology of the calcite examined in the KURT site will be used as important basic data for the radionuclide migration experiment in the future.

Effects of Diglyceride-Conjugated Linoleic Acid on Proliferation and Differentiation of 3T3-L1 Cells

  • Jeong, Jae-Hwang;Lee, Sang-Hwa;Hue, Jin-Joo;Lee, Yea-Eun;Lee, Young-Ho;Hong, Soon-Ki;Jeong, Seong-Woon;Nam, Sang-Yoon;Yun, Young-Won;Lee, Beom-Jun
    • Toxicological Research
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    • v.23 no.3
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    • pp.223-229
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    • 2007
  • Conjugated linoleic acid (CLA) has been recently reported to have an anti-obesity effect in animals and humans. The objective of this study was to investigate effects of diglyceride (DG)-CLA on proliferation and differentiation of 3T3-L1 preadipocytes. Cell proliferation was determined using WST-8 analysis and cell differentiation was determined by glycerol-3-phosphate dehydrogenase (GPDH) activity. Lipid accumulation in differentiating 3T3-L1 cells was determined by Oil red O staining. There were four experimental groups including vehicle control (DMSO), CLA, triglyceride (TG)-CLA, and DG-CLA. Treatments of CLA, TG-CLA, and DG-CLA at the concentrations of $10{\sim}1000{\mu}g/ml$ reduced proliferation of preconfluent 3T3-L1 cells in a dose-dependent manner. Among them CLA was the most effective in the proliferation inhibition of preconfluent 3T3-L1 cells with increasing concentrations. Treatments of CLA and DG-CLA at the concentration of $100{\mu}g/ml$ significantly inhibited differentiation of postconfluent 3T3-L1 cells as measured by GPOH activity (p<0.05). In addition, treatments of CLA, TG-CLA, and DG-CLA effectively inhibited lipid accumulation during differentiation of 3T3-L 1 cells. OG-CLA had the most inhibitory effect on the differentiation and lipid accumulation. These results suggest that the compounds including CLA have a respectable anti-obesity effect and that consumption of DG-CLA as a dietary oil may give a benefit for controlling overweight in humans.

Antibacterial activity of sodium phytate, sodium pyrophosphate, and sodium tripolyphosphate against Salmonella typhimurium in meats

  • Hue, Jin-Joo;Baek, Dong-Jin;Lee, Yea Eun;Lee, Ki Nam;Nam, Sang Yoon;Yun, Young Won;Jeong, Jae-Hwang;Lee, Sang-Hwa;Yoo, Han Sang;Lee, Beom Jun
    • Korean Journal of Veterinary Research
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    • v.47 no.4
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    • pp.449-456
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    • 2007
  • The approval of use of certain food-grade phosphates as food additives in a wide variety of meat products greatly stimulated research on the applications of phosphates in foods. Although phosphates have never been classified as antimicrobial agents, a number of investigators have reported that phosphates have antimicrobial activities. Phytic acid is a natural plant inositol hexaphosphate constituting 1-5% of most cereals, nuts, legumes, oil seeds, pollen, and spores. In this study, we investigated antibacterial activities of sodium phytate (SPT), sodium pyrophosphate (SPP), sodium tripolyphosphate (STPP) on Salmonella typhimurium in tryptic soy broth and in row meat media including chicken, pork and beef. SPY, SPP and STPP at the concentrations of 0.5 and 1% dose-dependently inhibited the growth of S. typhimurium in tryptic soy broth at various pHs. The antibacterial activities of SPT and STPP were the stronger than that of SPP. In chicken, pork, and beef, SPT, SPP and STPP at the concentrations of 0.1, 0.5 and 1.0% significantly inhibited the bacterial growth in a dose-dependant manner (p < 0.05). The antibacterial activities of SPT, SPP, and STPP were more effective in chicken than beef. SPT and STPP at the concentration of 1% reduced the bacterial count by about 2 log units. The addition of SPT, SPP and STPP at the concentration of 0.5% in meats increased the meat pHs by 0.28-0.48 units in chicken, pork, and beef. These results suggest that SPT and STPP were equally effective for the inhibition of bacterial growth both in TSB and meat media and that SPT can be used as an animal food additive for increasing shelf-life and functions of meats.

The Stability Evaluation Methods of Embankment on Soft Clay (연약지반 성토의 안정평가 방법)

  • Kang, Yea Mook;Lee, Dal Won;Kim, Ji Hoon;Kim, Tae Woo;Lim, Seong Hun
    • Korean Journal of Agricultural Science
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    • v.25 no.2
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    • pp.260-270
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    • 1998
  • The field tests were performed to suggest the rational method for stability evaluation of soft clay. The behavior of settlement-displacement obtained by field monitoring system was to compare and analyze the results of the observationed method, and to investigate the complex behavior of soft clay with filling height. The results of this study are summarized as follows. 1. The horizontal displacement was suddenly increased when physical properties of soft clay showed maximum values and the part of the turning point. The values of these properties were available to the fundamental data for stability evaluation. The shear deformation appeared that difference of the horizontal displacement was maximum values. 2. Although the stability of embankment by step filling showed the unstable part over the failure standard line, the embankment was confirmed stable. So the evaluation of the stability of embankment is reasonable to use the inclination of curve than failure standard line. 3. The horizontal displacement and relative settlement were increased as same ratio at improvement ground. Estimation of shear deformation using Terzaghi's modified bearing capacity should consider the relations of embankment load and undrained shear strength at nonimprovement ground, and minimum safety factor is recommended to use larger than 1.2. 4. Excess pore water pressure was increased with increasing of filling height and decreased with maintain the filling height. The embankment was unstable when filling height was exceed the evaluation standard line, and the behavior of excess pore water pressure and horizontal displacement could use as a standard of judgement of the filling velocity control because their behavior were agree with each other.

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The Consolidation Behavior on Soft Clay by Numerical Analysis (수치해석에 의한 연약지반의 압밀거동)

  • Kang, Yea Mook;Lee, Dal Won;Lim, Seong Hun;Yoon, Je Shik
    • Korean Journal of Agricultural Science
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    • v.25 no.2
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    • pp.235-246
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    • 1998
  • This study was performed to find the effect of parameters of numerical analysis model. To find the parameters of numerical analysis model, triaxial test and consolidation test were conducted and the results were compared and analyzed with various methods. Preloaded ground was analyzed with Hyperbolic and Modified Cam-Clay models. Hyperbolic model analysis result was good agreement with measured lateral displacement, and Modified Cam-Clay model agreed more than Hyperbolic model with settlement. When the parameters of models were changed, change of settlement on center of embankment and of maximum lateral displacement on distance 5m from end of embankment were compared. On Hyperbolic model the parameter K has large influence on settlement and lateral displacement. On Modified Cam-Clay model the parameters ${\Gamma}$ and M have large influence on settlement and lateral displacement, respectively.

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Consolidation Behavior of Vertical Drain in consideration of Smear Effect and Well Resistance (교란효과와 배수저항을 고려한 연직 배수재의 압밀 거동)

  • Kim, Tae Woo;Kang, Yea Mook;Lee, Dal Won
    • Korean Journal of Agricultural Science
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    • v.25 no.2
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    • pp.225-234
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    • 1998
  • This study was compared the degree of consolidation by Hyperbolic, Curve fitting, Asaoka's, Monden's methods using measured value with theoretical curve in consideration of smear effect and well resistance. The results of the study were summarized as follows ; 1. The degree of consolidation by Hyperbolic method was underestimated than the degree of consolidation by Curve fitting, Asaoka's, and Monden's methods. 2. Typical range of horizontal coefficient of consolidation was $C_h=(2{\sim}3)C_v$ in the case considering smear effect and well resistance, and $C_h=(0.5{\sim}2.5)C_v$ in the case disregarding smear effect and well resistance. 3. The degree of consolidation obtained by ground settlement monitoring was nearly same value when the coefficient of permeability of smear zone by back analysis was shown the half that of in-situ and the diameter of smear zone was shown double that of mendrel. 4. Increasing of diameter reduction ratio of drain, the time of consoildation was delayed. The affection of well resistance the case of small coefficient of permeability was much more than that in the case of large coefficient of permeability. It was recommended that design of diameter reduction of drain consider smear effect and well resistance.

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A SOA-based Application Model for Building Intelligent Construction Supply Chain Management Framework (지능형 건설물류관리 체계 구축을 위한 SOA 적용 모델 개발)

  • Shin, Tae-Hong;Chin, Sang-Yoon;Yoon, Su-Won;Kwon, Soon-Wook;Kim, Yea-Sang
    • Proceedings of the Korean Institute Of Construction Engineering and Management
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    • 2008.11a
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    • pp.733-737
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    • 2008
  • Construction supply chain management focused on materials in construction industry plays a critical role which controls the success and failure of a project. For the efficiency of construction supply chain management, the framework which provides project participants with the information originated from whole construction logistics steps without the omission and discontinuation of information flow is required. The new management framework that can support this environment is necessary because of setting up the complicated and distributed environment including logistics information management by intelligent equipment, co-working management with pre-framework legacy system and various devices(UMPC and PDA etc.) as the information confirmation and electrical transmission tool between the project participants different from former construction supply chain management environment while recently developing ubiquitous technologies such as RFID/USN and intelligent equipment to support logistics process. Therefore, the objective of this study is to introduce the concept of SOA (Service Oriented Architecture) as an alternative of effective information integration under the complex and distributed environment and to propose the SOA-based application model for building intelligent construction supply chain management framework.

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Settlement Characteristics of Large Drilled Shafts Embedded in Bed Rocks (암반에 근입된 대구경 현장타설말뚝의 침하특성)

  • Hong Won-Pyo;Yea Geu-Guwen;Nam Jung-Man;Lee Jae-Ho
    • Journal of the Korean Geotechnical Society
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    • v.21 no.5
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    • pp.111-122
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    • 2005
  • The data on the pile load tests performed on 35 large drilled shafts are analyzed to investigate the load-settlement characteristics of large drilled shafts embedded in bed rocks. Generally, the settlement of large drilled shafts embedded in bed rocks is too small to determine the ultimated load with application of the regulation in design code for either the total settlement or the residual settlement. Therefore, to determine the yield load of large drilled shafts embedded in bed rocks, p(load)-logS (settlement) curve method, which has been proposed originally for the driven pile, was applied to the investigation on the data of the pile load tests. This technique shows that the yield load can be determined accurately and easily rather than other conventional techniques such as P-S, logp-logS, S-logt, and P-S curve methods. An empirical equation is proposed to represent the relationship between pile load and settlement before the yield loading condition. And the settlement of piles was related with the depth embedded in rock as well as rock properties. Based on the investigation on the data of pile load tests, the resonable regulations f3r both the total settlement and the residual settlement are proposed to determine the yield load of large drilled shafts embedded in bed rocks.

Interaction of GAT1 with Ubiquitin-Specific Protease Usp14 in Synaptic Terminal (GAT1과 ubiquitin-specific protease Usp14의 결합)

  • Seog, Dae-Hyun;Kim, Sang-Jin;Joung, Young-Ju;Yea, Sung-Su;Park, Yeong-Hong;Kim, Moo-Seong;Moon, Il-Soo;Jang, Won-Hee
    • Journal of Life Science
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    • v.20 no.7
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    • pp.1005-1011
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    • 2010
  • $\gamma$-aminobutyric acid (GABA) is the major inhibitory neurotransmitter in the central nervous system. GABA transporters (GATs) control extracellular GABA levels by reuptake of released GABA from the synaptic cleft. However, how GATs are regulated has not yet been elucidated. Here, we used the yeast two-hybrid system to identify the specific binding protein(s) that interacts with the carboxyl (C)-terminal region of GAT1, the major isoform in the brain and find a specific interaction with the ubiquitin-specific protease 14 (Usp14), a deubiquitinating enzyme. Usp14 protein bound to the tail region of GAT1 and GAT2 but not to other GAT members in the yeast two-hybrid assay. The C-terminal region of Usp14 is essential for interaction with GAT1. In addition, these proteins showed specific interactions in the glutathione S-transferase (GST) pull-down assay. An antibody to GAT1 specifically co-immunoprecipitated Usp14 from mouse brain extracts. These results suggest that Usp14 may regulate the number of GAT1 at the cell surface.