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Pharmacophore Design for Anti-inflammatory Agent Targeting Interleukin-2 Inducible Tyrosine Kinase (Itk)

  • Chandrasekaran, Meganathan;Sakkiah, Sugunadevi;Thangapandian, Sundarapandian;Namadevan, Sundaraganesan;Kim, Hyong-Ha;Kim, Yong-Seong;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.31 no.11
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    • pp.3333-3340
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    • 2010
  • A three dimensional pharmacophore model was generated for the molecules which are responsible for anti-inflammatory activities targeting Interleukin-2 inducible tyrosine kinase (Itk). 16 structurally diverse molecules were selected as training set to generate the hypotheses using Discovery Studio v2.1. The best hypothesis, Hypo1, comprises two hydrogen bond acceptor (HBA), one hydrophobic aromatic (HA), one ring aromatic (RA) and shows high cost difference (63.71), high correlation coefficient (0.97) as well as low RMS deviation (0.81). Hypo1 has been further validated toward a test set, decoy set and Fischer's randomization method. Furthermore, Hypo1 was used to screen NCI and Maybridge databases. Finally, 2 hit molecules were identified as potential leads against Itk, which may be useful for future drug development.

Eutectic structure evolution of Al2O3-ZrO2-Y2O3 system for apotential hybrid solar cell application

  • Han, Young-Hwan;Yun, Jon-Do;Harada, Yohei;Jeong, Young-Keun;Makino, Taro;Kim, Kwang-Ho;Kwon, Se-Hun;Kim, Young-Moon;Kakegawa, Kazuyuki
    • Proceedings of the Materials Research Society of Korea Conference
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    • 2009.11a
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    • pp.11.1-11.1
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    • 2009
  • Ternary Al2O3.ZrO2.Y2O3 samples with a eutecticcomposition were prepared by slow cooling. The microstructural evolution wasobserved with X-ray diffraction (XRD), scanning electron microscopy (SEM). TheSEM observation of the ternary samples agreed with the XRD with a completion ofcrystallisation by slow cooling. The target materials commonly have 'cantaloupe skin' microstructures as shown inthe previous studies by Han et al. The nanocomposite may have experienceddifferent cooling rates with two different microstructures, near the surfacehaving experienced optimal conditions for the eutectic reaction during theircooling and thus formed the eutectic microstructure, near the centre havingexperienced a slower cooling rate. The crystallised eutectic ternary Al2O3.ZrO2.Y2O3 system had three different phaseswith a 3Y2O3. 5Al2O3 (yttrium.aluminiumgarnet phase), an alumina phase formed by the eutectic reaction, and a solidsolution of ZrO2 and Y2O3.

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Characterization of SID2 that is required for the production of salicylic acid by using β-GLUCURONIDASE and LUCIFERASE reporter system in Arabidoposis (리포트 시스템을 이용한 살리실산 생합성 유전자 SID2의 발현 해석)

  • Hong, Mi-Ju;Cheong, Mi-Sun;Lee, Ji-Young;Kim, Hun;Jeong, Jae-Cheol;Shen, Mingzhe;Ali, Zahir;Park, Bo-Kyung;Choi, Won-Kyun;Yun, Dae-Jin
    • Journal of Plant Biotechnology
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    • v.35 no.3
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    • pp.169-176
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    • 2008
  • Salicylic acid(SA) is a phytohormone that is related to plant defense mechanism. The SA accumulation is triggered by abiotic and biotic stresses. SA acts as a signal molecular compound mediating systemic acquired resistance and hypersensitive response in plant. Although the role of SA has been studied extensively, an understanding of the SA regulatory mechanism is still lacking in plants. In order to comprehend SA regulatory mechanism, we have been transformed with a SID2 promoter:GUS::LUC fusion construct into siz1-2 mutant and wild plant(Col-0). SIZ1 encodes SUMO E3 ligase and negatively regulates SA accumulation in plants. SID2(SALICYLIC ACID INDUCTION DEFICIENT2) is a crucial enzyme of SA biosynthesis. The Arabidopsis SID2 gene encodes isochorismate synthase(ICS) that controls SA level by conversion of chorismate to isochorismate. We compared the regulation of SID2 in wild-type and siz1-2 transgenic plants that express SID2 promoter:GUS::LUC constructs respectively. The expressions of $\beta$-GLUCURONIDASE and LUCIFERASE were higher in siz 1-2 transgenic plant without any stress treatment. SID2 promoter:GUS::LUC/siz1-2 transgenic plant will be used as a starting material for isolation of siz1-2 suppressor mutants and genes involved in SA-mediated stress signaling pathway.

Core region and optical properties of Er3+ doped Y3Al5O12 single crystals (Er3+ doped Y3Al5O12 단결정의 core 영역 및 광학적 특성)

  • Shim, Jang Bo;Lee, Young Jin;Kang, Jin Ki;Lee, Young Kuk
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.25 no.3
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    • pp.111-115
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    • 2015
  • $Er^{3+}$ doped $Y_3Al_5O_{12}$ (Er:YAG) single crystals, in which the concentrations of $Er^{3+}$ ion were 5, 7.3, 8, and 10 at.%, were grown by the Czochralski method under nitrogen atmosphere. The <111> oriented Er:YAG single crystals with diameters of up to 50 mm were grown at a pulling rate of 1.0 mm/h and rotation rate of 10 rpm. The thick part of the core region was generated mainly when there was a diameter change during the crystal growth. The concentrations of $Er^{3+}$ ion in the crystals were the same as it was in the melt. $Er^{3+}$ concentration of core region was slightly higher than the other regions in the compositional analysis. The fluorescence lifetime was saturated according to the increase of $Er^{3+}$ doping concentrations.

Synthesis of Au/TiO2 Core-Shell Nanoparticles by Using TTIP/TEOA Mixed Solution (TTIP/TEOA 혼합용액을 이용한 Au/TiO2 Core-Shell 구조 나노입자 합성)

  • Kwon, Hyun-Woo;Lim, Young-Min;Yu, Yeon-Tae
    • Korean Journal of Materials Research
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    • v.16 no.8
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    • pp.524-528
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    • 2006
  • On the synthesis of Au/$TiO_2$ core-shell structure nanoparticle, the effect of concentration of $Ti^{4+}$ and reaction temperature on the morphology and optical property of Au/$TiO_2$ core-shell nanoparticles is examined. A gold colloid was prepared by $HAuCl_4{\cdot}4H_2O\;and\;C_6H_5Na_3{\cdot}2H_2O$. Titanium stock solution was prepared by mixing solution of titanium(IV) isopropoxide (TTIP) and triethanolamine (TEOA). The concentrations of $Ti^{4+}$ stock solution were adjusted to $10.01{\sim}0.3$ mM, and then the gold colloid is added to the $Ti^{4+}$ stock solution. Au/$TiO_2$ core-shell structure nanoparticles could be prepared by the hydrolysis of the $Ti^{4+}$ stock solution at $80^{\circ}C$. The size of synthesized Au nanoparticles was 15 nm. The thickness of $TiO_2$ shell on the surface of gold particles was about 10 nm. The absorption peak of synthesized Au/$TiO_2$ core-shell nanoparticles shifted towards the red end of the spectrum by about 3 nm because of the formation of $TiO_2$ shell on the surface of gold particles. The good $TiO_2$ shell is produced when $Ti^{4+}$ concentration is varied between 0.01 and 0.05 mM, and reaction temperature is maintained at $80^{\circ}C$. The crystal structure of $TiO_2$ shell was amorphous.

Uncontrolled Manifold Analysis of Whole Body CoM of the Elderly: The Effect of Training using the Core Exercise Equipment

  • Park, Da Won;Koh, Kyung;Park, Yang Sun;Shim, Jae Kun
    • Korean Journal of Applied Biomechanics
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    • v.28 no.4
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    • pp.213-218
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    • 2018
  • Objective: The purpose of this study was to examine the effect of the core muscle strength enhancement of the elderly on 8 weeks training using the core exercise equipment for the elderly on the ability to control the whole-body center of mass in posture stabilization. Method: 16 females (10 exercise group, 6 control group) participated in this study. Exercise group took part in the core strength training program for 8 weeks with total of 16 repetitions (2 repetitions per week) using a training device. External perturbation during standing as pulling force applied at the pelvic level in the anterior direction was provided to the subject. In a UCM model, the controller selects within the space of elemental variables a subspace (a manifold, UCM) corresponding to a value of a performance variable that needs to be stabilized. In the present study, we were interested in how movements of the individual segment center of mass (elemental variables) affect the whole-body center of mass (the performance variable) during balance control. Results: At the variance of task-irrelevant space, there was significant $test^*$ group interactions ($F_{1,16}=7.482$, p<.05). However, there were no significant main effect of the test ($F_{1,16}=.899$, p>.05) and group ($F_{1,16}=1.039$, p>.05). At the variance of task-relevant space, there was significant $test^*$ group interactions ($F_{1,16}=7.382$, p<.05). However, there were no significant main effect of the test ($F_{1,16}=.754$, p>.05) and group ($F_{1,16}=1.106$, p>.05). Conclusion: The results of this study showed that the 8 weeks training through the core training equipment for the elderly showed a significant decrease in the $Vcm_{TIR}$ and $Vcm_{TR}$. This result indicates that the core strength training affects the trunk stiffness control strategy to maintain balance in the standing position by minimizing total variability of individual segment CMs.

InGaAs/InAlAs Quantum Cascade Lasers Grown by using Metal-organic Vapor-phase Epitaxy

  • Kim, Dong Hak;Jeong, Hae Yong;Choi, Young Su;Park, Deoksoo;Jeon, Young-Jin;Jun, Dong-Hwan
    • Applied Science and Convergence Technology
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    • v.26 no.5
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    • pp.139-142
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    • 2017
  • In this paper, InP-based InGaAs/InAlAs quantum cascade lasers(QCLs) providing nearly zero emission wavelength mismatch between the measured emission wavelength and the designed transition wavelength of QCLs is presented. The zero emission wavelength mismatch of QCLs influenced by both the accurate compositions and thicknesses of the low-pressure metal-organic vapor-phase epitaxy(MOVPE) grown InGaAs and InAlAs layers throughout the core and the abrupt composition transitions between InGaAs and InAlAs layers. The abrupt interfaces between InGaAs and InAlAs layers have been achieved throughout the core structure by means of controlling individually purged vent/run valves of a closed coupled showerhead reactor. In addition, maintaining substrate temperature constant during InGaAs/InAlAs core growth was a partial factor of uniformity improvement of QCLs. These approaches for reducing the possible discrepancies between the designed and MOVPE grown epitaxial structures could lead to improvement of QCL performance.

P56 LCK Inhibitor Identification by Pharmacophore Modelling and Molecular Docking

  • Bharatham, Nagakumar;Bharatham, Kavitha;Lee, Keun-Woo
    • Bulletin of the Korean Chemical Society
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    • v.28 no.2
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    • pp.200-206
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    • 2007
  • Pharmacophore models for lymphocyte-specific protein tyrosine kinase (P56 LCK) were developed using CATALYST HypoGen with a training set comprising of 25 different P56 LCK inhibitors. The best quantitative pharmacophore hypothesis comprises of one hydrogen bond acceptor, one hydrogen bond donor, one hydrophobic aliphatic and one ring aromatic features with correlation coefficient of 0.941, root mean square deviation (RMSD) of 0.933 and cost difference (null cost-total cost) of 66.23. The pharmacophore model was validated by two methods and the validated model was further used to search databases for new compounds with good estimated LCK inhibitory activity. These compounds were evaluated for their binding properties at the active site by molecular docking studies using GOLD software. The compounds with good estimated activity and docking scores were evaluated for physiological properties based on Lipinski's rules. Finally 68 compounds satisfied all the properties required to be a successful inhibitor candidate.

Identification of another calmodulin-binding domain at the C-terminal region of AtCBP63

  • Kim, Sun-Ho;Kang, Yun-Hwan;Han, Hay-Ju;Bae, Dong-Won;Kim, Min-Chul;Lim, Chae-Oh;Chung, Woo-Sik
    • Journal of Plant Biotechnology
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    • v.36 no.1
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    • pp.53-58
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    • 2009
  • Calcium signals can be transduced by binding calmodulin (CaM), a $Ca^{2+}$ sensor in eukaryotes, is known to be involved in the regulation of diverse cellular functions. We isolated a CaM-binding protein 63 kD (AtCBP63) from the pathogen-treated Arabidopsis cDNA expression library. Recently, AtCBP63 was identified as a CaM bining protein. The CaM binding domain of AtCBP63 was reported to be located in its N-terminal region, In this study, however, we showed that ACaM2 could specifically bind to second CaM-binding domain (CaMBD) of AtCBP63 at the C-terminal region. The specific binding of CaM to CaM binding domain was confirmed by a gel mobility shift assay, a split ubiquitin assay, site-directed mutagenesis, and a competition assay using a $Ca^{2+}$/CaM-dependent enzyme. The gene expression of AtCBP63 was induced by pathogens and pathogens related second messengers. This result suggests that a CaM binding protein, AtCBP63, may play role in pathogen defense signaling pathway.

Vertical Variation of Sediment Structure and Geochemical Characteristics of Core Sediment in Nakdong River Midstream (낙동강 중류의 주상퇴적물에서 나타나는 퇴적 구조와 지화학적 특성의 수직적 변화)

  • Kim, Shin;Lee, Kyu Yeol;Kim, Ju Eon;Lee, Kwon Chul;Ahn, Jung Min;Lee, Injung;Jung, Kang Young;Im, Tae Hyo
    • Journal of Korean Society on Water Environment
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    • v.31 no.3
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    • pp.304-312
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    • 2015
  • In this study, we tried to determine the vertical variation of sediment structure and geochemical characteristics, core sediment was collected in the Nakdong River midstream on August, 2014. Core sediment mainly composed of sand (51.48%) and silt (46.21%) and coarsing upward changed from sM to mS facies. IL and TOC were decreased from lower to upper layer. C/N ratio was lower than 10 so the organic matters were originated from underwater creatures and C/S ratio was decreased from lower to upper layer. Heavy metal (Al, Fe, Zn, Cr, Pb, Ni, Cu, Cd) content were decreased from lower to upper layer and seriously polluted condition is not. These results are thought to be due to the effect of natural and anthropogenic in the fluctuation of flow.