• 제목/요약/키워드: c-Src

검색결과 95건 처리시간 0.026초

합성단면의 콘크리트 크리프 해석을 위한 이완계수법 (Stress Relaxation Coefficient Method for Concrete Creep Analysis of Composite Sections)

  • 연정흠;경태현;김다나
    • 콘크리트학회논문집
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    • 제23권1호
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    • pp.77-86
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    • 2011
  • 복합구조의 합성단면에서 콘크리트 크리프변형은 합성단면에 추가 변형을 발생시키며, 장기변형의 일부 구속에 의한 응력이완은 콘크리트단면에 도입된 선압축응력의 심각한 손실을 초래할 수 있다. 이 논문에서는 복잡한 합성단면의 콘크리트 크리프변형에 대해 공학적인 목적에서 단순 해석이 가능한 이완계수법을 유도하고, 이완계수법에 요구되는 응력이완계수 식을 제안하였다. 이완계수법은 크리프계수와 합성단면의 환산단면특성 및 하중특성을 매개변수로 사용하는 균등 크리프계수 단계별계산법(CC-SSM)과 같은 방법으로 유도되었다. 제안된 이완계수 식에 의한 응력이완계법의 오차는 CC-SSM으로부터 평가된 이완계수법의 평균 응력이완계수에 의한 오차보다 향상되었으며, 자유상태에서 크리프변형에 대한 제안식에 의한 이완계수법 반응의 평균오차율은 3보다 크지 않은 크리프계수에 대해 1.2%보다 작으며, 99% 신뢰도에서 최대 3.3%이었다. 제안된 응력이완계수 식은 크리프변형에 대한 합성단면의 내부구속 정도를 반영하며, 외부구속 효과를 분석하기 위한 전산구조해석에서 응력이완계수가 적용된 유효탄성계수는 합성단면의 요소에 대한 강성 계산에 효율적으로 적용될 수 있다.

고주파 부분방전 측정에 의한 초고압 접속함 신뢰성 평가 기술 (A Evaluation Technique for Reliability of Extra-High Voltage Cable Accessories using High Frequency Partial Discharge Measurement)

  • 신두성;이창영;김충식;전승익;김동욱;박완기
    • 대한전기학회논문지:전기물성ㆍ응용부문C
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    • 제49권3호
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    • pp.186-195
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    • 2000
  • In this paper, partial discharge (PD) measurement was performed to evaluate the quality of the cable joint and termination constructions. The resistive coupling technique for PD detection using resistivity of semiconducting layer of the cable in the accessories, such as joints and terminations. With high frequency PD (HEPD) measurement, an excellent sensitivity below 20pC could be achieved under unshielded condition. The localization of the defects in the accessories could be identified. During heating cycle, PDs were monitored and analyzed. At that time, the PDs were dependent on the temperature of the heating cycle and showed cyclic behaviors, which were attributed to local delamination of the interfaces, between epoxy unit and stress relief cone(SRC) and between SRC and cable, due to the difference of thermal expansion. As a conclusion, HFPD measurement technique was proven to be an effective diagnostic method for qualification of extra high voltage (EHV) cable accessories. With this technique, the optimal design of the components of the accessories could be verified not only in an early stage but also under operating condition. This technique would result in the improvement of the reliability of the EHV cable accessories.

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가열온도, 가열시간 및 부형제의 첨가량이 도축 반추위 내용물의 자일란, 셀룰로오스 및 전분 분해효소 활성에 미치는 영향 (Effects of Temperature and Time for Heating and Filler Content on the Activities of Xylanase, Cellulase and Amylase in Slaughterhouse Rumen Content)

  • 원미영;이도형;김은중
    • 한국초지조사료학회지
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    • 제33권1호
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    • pp.58-66
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    • 2013
  • 본 연구는 도축장에서 폐기되는 도축 반추위 내용물을 사일리지 혹은 TMR (total mixed ration) 사료 첨가용 효소제로 개발하기 위한 목적으로 수행되었다. 도축 반추위 내용물에는 상당한 수분이 함유되어 있어, 적절한 건조과정을 거치지 않고서는 그 활용이 원활하지 않다. 그러나 효소는 열에 민감한 단백질로 구성되어 있기 때문에 적절한 건조 조건의 개발이 필요하다. 본 연구에서는 통계적 방법을 이용하여 가열온도(60, 75, $90^{\circ}C$), 가열시간(12, 30, 48 시간) 및 부형제의 비율(12, 22.5, 33%)이 도축 반추위 내용물에 함유된 다양한 효소활성에 미치는 효과를 분석하였다. 총 3가지 효소, xylan 분해효소, 셀룰로오스 분해효소 및 전분 분해효소를 검토하였고, 각 효소활성들에 대한 각 요인들의 효과가 매우 다양하게 나타났다(p<0.05). 셀룰로오스 분해효소와 전분 분해효소의 활성은 가열온도가 증가함에 따라 감소하였으며(p<0.05), xylan 분해해소는 열에 대한 안전성이 다른 효소들에 비하여 우수하였다. 자일란, 셀룰로오스, 전분 분해효소를 증가시키는 적정 부형제의 비율은 22.5, 12 그리고 33%로 나타났다. 비록 3가지 효소들의 제형화에 있어 공통적으로 적용될 수 있는 최적점을 도출하지는 못하였으나, 본 연구결과에서 얻어진 효소들의 반응 값들을 이용하여 목적하는 효소에 따라서 다양한 방법으로 적용이 가능할 것으로 판단된다.

Differentially Expressed Genes by Inhibition of C-terminal Src Kinase by siRNA in Human Vascular Smooth Muscle Cells and Their Association with Blood Pressure

  • Hong, Kyung-Won;Shin, Young-Bin;Kim, Koan-Hoi;Oh, Berm-Seok
    • Genomics & Informatics
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    • 제9권3호
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    • pp.102-113
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    • 2011
  • C-terminal SRC kinase (CSK) is a ubiquitously expressed, cytosolic enzyme that phosphorylates and inactivates several SRC family protein tyrosine kinases. Recent genomewide association studies have implicated CSK in the regulation of blood pressure. The current study aim is to determine the blood pressure association of the genes regulated by CSK down-regulation. The CSK mRNA expression was downregulated in vascular smooth muscle cells using small interfering RNA (siRNA). CSK mRNA levels fell by 90% in cells that were treated with CSK siRNA; the RNA from these cells was examined by microarray using the Illumina HumanRef-8 v3 platform, which comprises 24,526 reference mRNA probes. On treatment with CSK siRNA, 19 genes were downregulated by more than 2-fold and 13 genes were upregulated by more than 2-fold. Three (CANX, SLC30A7, and HMOX1) of them revealed more than 3 fold differential expression. Interestingly, the HMOX1 SNPs were associated with diastolic blood pressure in the 7551 Koreans using Korea Association REsource data, and the result was supported by the other reports that HMOX1 linked to blood vessel maintenance. Among the remaining 29 differentially expressed genes, seven (SSBP1, CDH2, YWHAE, ME2, PFTK1, G3BP2, and TUFT1) revealed association with both systolic and diastolic blood pressures. The CDH2 gene was linked to blood pressures. Conclusively, we identified 32 differentially expressed genes which were regulated by CSK reduction, and two (HOMX1 and CDH2) of them might influence the blood pressure regulation through CSK pathway.

The Src/PLC/PKC/MEK/ERK Signaling Pathway Is Involved in Aortic Smooth Muscle Cell Proliferation induced by Glycated LDL

  • Cho, Hyun-Mi;Choi, Sung Hee;Hwang, Ki-Chul;Oh, Sue-Young;Kim, Ho-Gyung;Yoon, Deok-Hyo;Choi, Myung-Ae;Lim, So Yeon;Song, Heesang;Jang, Yangsoo;Kim, Tae Woong
    • Molecules and Cells
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    • 제19권1호
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    • pp.60-66
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    • 2005
  • Low density lipoproteins (LDL) play important roles in the pathogenesis of atherosclerosis. Diabetes is associated with accelerated atherosclerosis leading to cardiovascular disease in diabetic patients. Although LDL stimulates the proliferation of arterial smooth muscle cells (SMC), the mechanisms are not fully understood. We examined the effects of native LDL and glycated LDL on the extracellular signal-regulated kinase (ERK) pathway. Addition of native and glycated LDL to rat aorta SMCs (RASMCs) stimulated ERK phosphorylation. ERK phosphorylation was not affected by exposure to the $Ca^{2+}$ chelator BAPTA-AM but inhibition of protein kinase C (PKC) with GF109203X, inhibition of Src kinase with PP1 ($5{\mu}M$) and inhibition of phospholipase C (PLC) with U73122/U73343 ($5{\mu}M$) all reduced ERK phosphorylation in response to glycated LDL. In addition, pretreatment of the RASMCs with a cell-permeable mitogen-activated protein kinase kinase (MEK) inhibitor (PD98059, $5{\mu}M$) markedly decreased ERK phosphorylation in response to native and glycated LDL. These findings indicate that ERK phosphorylation in response to glycated LDL involves the activation of PKC, PLC, and MEK, but is independent of intracellular $Ca^{2+}$.

4-(Tert-butyl)-2,6-bis(1-phenylethyl)phenol induces pro-apoptotic activity

  • Kim, Jun Ho;Lee, Yunmi;Kim, Mi-Yeon;Cho, Jae Youl
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권3호
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    • pp.253-259
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    • 2016
  • Previously, we found that KTH-13 isolated from the butanol fraction of Cordyceps bassiana (Cb-BF) displayed anti-cancer activity. To improve its antiproliferative activity and production yield, we employed a total synthetic approach and derivatized KTH-13 to obtain chemical analogs. In this study, one KTH-13 derivative, 4-(tert-butyl)-2,6-bis(1-phenylethyl)phenol (KTH-13-t-Bu), was selected to test its anti-cancer activity. KTH-13-t-Bu diminished the proliferation of C6 glioma, MDA-MB-231, LoVo, and HCT-15 cells. KTH-13-t-Bu induced morphological changes in C6 glioma cells in a dose-dependent manner. KTH-13-t-Bu also increased the level of early apoptotic cells stained with annexin V-FITC. Furthermore, KTH-13-t-Bu increased the levels of cleaved caspase-3 and -9. In contrast, KTH-13-t-Bu upregulated the levels of pro- and cleaved forms of caspase-3, -8, and -9 and Bcl- 2. Phospho-STAT3, phospho-Src, and phospho-AKT levels were also diminished by KTH13-t-Bu treatment. Therefore, these results strongly suggest that KTH-13-t-Bu can be considered a novel anti-cancer drug displaying pro-apoptotic activity.

Comparison of Some 3-(Substituted-Benzylidene)-1, 3-Dihydro-Indolin Derivatives as Ligands of Tyrosine Kinase Based on Binding Mode Studies and Biological Assay

  • Olgen, Sureyya
    • Archives of Pharmacal Research
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    • 제29권11호
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    • pp.1006-1017
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    • 2006
  • A series of 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one, 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione and 2, 2'-dithiobis 3-(substituted-benylidene)-1, 3-dihydro-indole derivatives was investigated as inhibitor of $p60^{c-Src}$tyrosine kinase by performing receptor docking studies and inhibitory activity toward tyrosine phosphorylation. Some compounds were shown to be docked at the site, where the selective inhibitor PP1 [1-tert-Butyl-3-p-tolyl-1H-pyrazolo[3,4-d]pyrimidine-4-yl-amine] was embedded at the enzyme active site. Evaluation of all compounds for the interactions with the parameters of lowest binding energy levels, capability of hydrogen bond formations and superimposibility on enzyme active site by docking studies, it can be assumed that 3-(substituted-benzylidene)-1, 3-dihydro-indolin-2-one and thione derivatives have better interaction with enzyme active site then 2, 2'-dithiobis 3-(substituted-benzylidene)-1, 3-dihydro indole derivatives. The test results for the inhibitory activity against tyrosine kinase by Elisa method revealed that 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-thione derivatives have more activity then 3-(substituted-benylidene)-1, 3-dihydro- indolin-2-one derivatives.

A Screening Method for Src Homology 3 Domain Binding Blockers Based on Ras Signaling Pathway

  • Ko, Woo-Suk;Yoon, Sun-Young;Kim, Jae-Won;Lee, Choong-Eun;Han, Mi-Young
    • BMB Reports
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    • 제30권5호
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    • pp.303-307
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    • 1997
  • Grb2, which is composed of a Src homology 2 (SH2) domain and two Src homology 3 (SH3) domains, is known to serve as an adaptor protein in signaling for Ras activation. Thus, a blocker of the Grb2 interactions with other proteins can be a potential candidate for an anticancer drug. In this study, we have developed a high throughput screening method for SH3 domain binding ligands and blockers. Firstly, we made and purified the glutathione S-transferase (GST)-fusion proteins with the Grb2 SH2 and SH3 domains, and the entire Grb2. This method measures the binding of a biotin-labeled oligopeptide, derived from a Grb2/SH3 binding motif in the hSos, to the GST-fusion proteins, which are precoated as glutathione S-transferase fusion protein on a solid phase. When $1\;{\mu}g$ of each fusion protein was used to coat the wells, both N- and C- terminal SH3 the domains as well as the whole of Grb2 were able to interact with the biotin-conjugated ligand peptide, while the SH2 domain and GST alone showed no binding affinity. Although N- and C- terminal SH3 domains showed an increase of binding to the ligand peptide in proportion to the amount of peptide, the GST fusion protein with Grb2 demonstrated much higher binding affinity. GST-Grb2 coating on the solid phase showed a saturation curve; 66 and 84% of the maximal binding was observed at 100 and 300 ng/$100\;{\mu}l$, respectively. This binding assay system was peptide sequence-specific, showing a dose-dependent inhibition with the unlabeled peptide of SH3 binding motif. Several other peptides, such as SH2 domain binding motifs and PTB domain binding motif, were ineffective to inhibit the binding to the biotin-conjugated ligand peptide. These results suggest that our method may be useful to screen for new anticancer drug candidates which can block the signaling pathways mediated by SH3 domain binding.

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Pyrrole-Derivative of Chalcone, (E)-3-Phenyl-1-(2-Pyrrolyl)-2-Propenone, Inhibits Inflammatory Responses via Inhibition of Src, Syk, and TAK1 Kinase Activities

  • Yang, Sungjae;Kim, Yong;Jeong, Deok;Kim, Jun Ho;Kim, Sunggyu;Son, Young-Jin;Yoo, Byong Chul;Jeong, Eun Jeong;Kim, Tae Woong;Han Lee, In-Sook;Cho, Jae Youl
    • Biomolecules & Therapeutics
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    • 제24권6호
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    • pp.595-603
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    • 2016
  • (E)-3-Phenyl-1-(2-pyrrolyl)-2-propenone (PPP) is a pyrrole derivative of chalcone, in which the B-ring of chalcone linked to ${\beta}$-carbon is replaced by pyrrole group. While pyrrole has been studied for possible Src inhibition activity, chalcone, especially the substituents on the B-ring, has shown pharmaceutical, anti-inflammatory, and anti-oxidant properties via inhibition of NF-${\kappa}B$ activity. Our study is aimed to investigate whether this novel synthetic compound retains or enhances the pharmaceutically beneficial activities from the both structures. For this purpose, inflammatory responses of lipopolysaccharide (LPS)-treated RAW264.7 cells were analyzed. Nitric oxide (NO) production, inducible NO synthase (iNOS) and tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$) mRNA expression, and the intracellular inflammatory signaling cascade were measured. Interestingly, PPP strongly inhibited NO release in a dose-dependent manner. To further investigate this anti-inflammatory activity, we identified molecular pathways by immunoblot analyses of nuclear fractions and whole cell lysates prepared from LPS-stimulated RAW264.7 cells with or without PPP pretreatment. The nuclear levels of p50, c-Jun, and c-Fos were significantly inhibited when cells were exposed to PPP. Moreover, according to the luciferase reporter gene assay after cotransfection with either TRIF or MyD88 in HEK293 cells, NF-${\kappa}B$-mediated luciferase activity dose-dependently diminished. Additionally, it was confirmed that PPP dampens the upstream signaling cascade of NF-${\kappa}B$ and AP-1 activation. Thus, PPP inhibited Syk, Src, and TAK1 activities induced by LPS or induced by overexpression of these genes. Therefore, our results suggest that PPP displays anti-inflammatory activity via inhibition of Syk, Src, and TAK1 activity, which may be developed as a novel anti-inflammatory drug.

Secretion of MCP-1, IL-8 and IL-6 Induced by House Dust Mite, Dermatophagoides pteronissinus in Human Eosinophilic EoL-1 Cells

  • Lee, Ji-Sook;Kim, In-Sik;Yun, Chi-Young
    • Animal cells and systems
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    • 제13권4호
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    • pp.391-397
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    • 2009
  • The house dust mite (Dermatophagoides pteronissinus) is an important factor in triggering allergic diseases. The function of eosinophils, particularly in the production of cytokine or chemokine, is critical in understanding the pathogenesis of inflammatory diseases. In this study, we examined whether D. pteronissinus extract (DpE) induces the expression of monocyte chemotactic protein 1 (MCP-1)/CCL2, IL-8/CXCL8, and IL-6 that mediate in the infiltration and activation of immune cells and in its signaling mechanism in the human eosinophilic cell line, EoL-1. DpE increased the mRNA and protein expression of MCP-1, IL-8, and IL-6 in a time- and dose-dependent course in EoL-1 cells. In our experiments using signal-specific inhibitors, we found that the increased expression of MCP-1, IL-8, and IL-6 due to DpE is associated with Src family tyrosine kinase and protein kinase C $\delta$ (PKC $\delta$). In addition, the activation of extracellular signal-regulated kinase (ERK) is required for MCP-1 and IL-8 expression while p38 mitogen-activated protein kinase (MAPK) is involved in IL-6 expression. DpE induced the phosphorylation of ERK and p38 MAPK. PP2, an inhibitor of Src family tyrosine kinase, and rottlerin, an inhibitor of PKC $\delta$, blocked the activation of ERK and p38 MAPK. DpE induces the activation of ERK and p38 MAPK via Src family tyrosine kinase and PKC $\delta$ for MCP-1, IL-8, or IL-6 production. Increased cytokine release due to the house dust mite and the characterization of its signal transduction may be valuable in understanding the eosinophil-related pathogenic mechanism of inflammatory diseases.