• Title/Summary/Keyword: amplification factor

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Deoxypodophyllotoxin Inhibits Cell Growth and Induces Apoptosis by Blocking EGFR and MET in Gefitinib-Resistant Non-Small Cell Lung Cancer

  • Kim, Han Sol;Oh, Ha-Na;Kwak, Ah-Won;Kim, Eunae;Lee, Mee-Hyun;Seo, Ji-Hye;Cho, Seung-Sik;Yoon, Goo;Chae, Jung-Il;Shim, Jung-Hyun
    • Journal of Microbiology and Biotechnology
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    • v.31 no.4
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    • pp.559-569
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    • 2021
  • As one of the major types of lung cancer, non-small cell lung cancer (NSCLC) accounts for the majority of cancer-related deaths worldwide. Treatments for NSCLC includes surgery, chemotherapy, and targeted therapy. Among the targeted therapies, resistance to inhibitors of the epidermal growth factor receptor (EGFR) is common and remains a problem to be solved. MET (hepatocyte growth factor receptor) amplification is one of the major causes of EGFR-tyrosine kinase inhibitor (TKI) resistance. Therefore, there exists a need to find new and more efficacious therapies. Deoxypodophyllotoxin (DPT) extracted from Anthriscus sylvestris roots exhibits various pharmacological activities including anti-inflammation and anti-cancer effects. In this study we sought to determine the anti-cancer effects of DPT on HCC827GR cells, which are resistant to gefitinib (EGFR-TKI) due to regulation of EGFR and MET and their related signaling pathways. To identify the direct binding of DPT to EGFR and MET, we performed pull-down, ATP-binding, and kinase assays. DPT exhibited competitive binding with ATP against the network kinases EGFR and MET and reduced their activities. Also, DPT suppressed the expression of p-EGFR and p-MET as well as their downstreat proteins p-ErbB3, p-AKT, and p-ERK. The treatment of HCC827GR cells with DPT induced high ROS generation that led to endoplasmic-reticulum stress. Accordingly, loss of mitochondrial membrane potential and apoptosis by multi-caspase activation were observed. In conclusion, these results demonstrate the apoptotic effects of DPT on HCC827GR cells and signify the potential of DPT to serve as an adjuvant anti-cancer drug by simultaneously inhibiting EGFR and MET.

Effects of Post-Tensioning Tendons and Vehicle Speeds on Dynamic Response of Concrete-Filled Steel Tubular Tied Arch Girder (긴장재 및 차량속도 변화에 따른 콘크리트 충전 타이드 아치형 거더의 동적거동)

  • Roh, Hwasung;Hong, Sanghyun;Park, Kyunghoon;Lee, Jong Seh
    • KSCE Journal of Civil and Environmental Engineering Research
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    • v.31 no.3A
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    • pp.163-172
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    • 2011
  • The CFTA girder developed is a concrete filled steel tubular system with arched shape and external post-tensioning (PT) tendons which control the initial camber and the bending stress of the girder. In the present study the effects of the PT tendons on the dynamic behavior of the girder subjected to a moving vehicle load are numerically investigated. Various levels for the tendon quantity and the tendon forces are considered, using the existing FE model of the girder. The vehicle considered is a DB-24 truck and is modeled with two tracks-three axles. Equivalent-load pulse time histories are applied to each node to simulate the moving vehicle, depending on the time of arrival and the discretization. The vehicle speeds are varied from 40 km/hr to 100 km/hr with increment of 20 km/hr. The analysis results show that the tendon forces do not produce any influences on the dynamic responses of the girder. However the dymamic deflection of the girder increases when a smaller amount of tendons is used. The Dynamic Amplification Factors (DAF) are evaluated based on the static and dynamic responses. Much lower values of the DAF are obtained, even no tendons applied, than those provided by the design criteria of the AASHTO LRFD and the Korea Highway Standard Specification.

Development of Permanent Displacement Model for Seismic Mountain Slope (지진 시 산사면의 영구변위 추정식 개발)

  • Lee, Jong-Hoo;Park, Duhee;Ahn, Jae-Kwang;Park, Inn-Joon
    • Journal of the Korean Geotechnical Society
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    • v.31 no.4
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    • pp.57-66
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    • 2015
  • Empirical seismic displacement equations based on the Newmark sliding block method are widely used to develop seismic landslide hazard map. Most proposed equations have been developed for embankments and landfills, and do not consider the dynamic response of sliding block. Therefore, they cannot be applied to Korean mountain slopes composed of thin, uniform soil-layer underlain by an inclined bedrock parallel to the slope. In this paper, a series of two-dimensional dynamic nonlinear finite difference analyses were performed to estimate the permanent seismic slope displacement. The seismic displacement of mountain slopes was calculated using the Newmark method and the equivalent acceleration time history. The calculated seismic displacements of the mountain slopes were compared to a widely used empirical displacement model. We show that the displacement prediction is significantly enhanced if the slope is modeled as a flexible sliding mass and the amplification characteristics are accounted for. Regression equation, which uses PGA, PGV, Arias intensity of the ground motion and the fundamental period of soil layer, is shown to provide a reliable estimate of the sliding displacement. Furthermore, the empirical equation is shown to reliably predict the hazard category.

Impact Evaluation of Rubber Type, Hardness and Induced Prestress Force on the Dynamic Properties of a Damper (감쇠장치의 동적특성에 대한 고무의 종류, 경도 및 프리스트레스력의 영향 평가)

  • Im, Chae-Rim;Yang, Keun-Hyeok;Mun, Ju-Hyun;Won, Eun-Bee
    • Journal of the Korea institute for structural maintenance and inspection
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    • v.26 no.6
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    • pp.167-174
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    • 2022
  • The objective of this study is to evaluate the dynamic properties of DUS (damping-up system) composed of the materials with excellent damping capacity, and to compare with those of the conventional hangar bolt. The main parameters are the type and hardness (𝜂H), of rubber and the prestress force (value converted from the compression strain (𝜂R) in the stress-strain relationship of rubber). The dynamic properties were examined from the natural frequency (𝜔n), maximum response acceleration (Am), amplification coefficient (𝛼p), maximum relative displacement (𝚫m), and damping ratio (𝜉D). The test results showed that the Am, 𝛼p, and 𝚫m values of DUS were 46.3%, 46.6% and 62.9% lower, respectively, and the 𝜉D value was 3.89 times higher, when compared to those of the conventional hangar bolt. In particular, the 𝛼p value was 1.3 for DUS, and 2.45 for the conventional hanger bolt, which were similar to those of rigid and flexible components specified in KDS 41 17 00, respectively. Consequently, in the optimal details of DUS, the 𝜂H values of 50 and 45 were required for the NR (natural rubber) and EPDM (ethylene propylene diene monomer), and the 𝜂R value of 5% was also recommended.

Reliability of mortar filling layer void length in in-service ballastless track-bridge system of HSR

  • Binbin He;Sheng Wen;Yulin Feng;Lizhong Jiang;Wangbao Zhou
    • Steel and Composite Structures
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    • v.47 no.1
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    • pp.91-102
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    • 2023
  • To study the evaluation standard and control limit of mortar filling layer void length, in this paper, the train sub-model was developed by MATLAB and the track-bridge sub-model considering the mortar filling layer void was established by ANSYS. The two sub-models were assembled into a train-track-bridge coupling dynamic model through the wheel-rail contact relationship, and the validity was corroborated by the coupling dynamic model with the literature model. Considering the randomness of fastening stiffness, mortar elastic modulus, length of mortar filling layer void, and pier settlement, the test points were designed by the Box-Behnken method based on Design-Expert software. The coupled dynamic model was calculated, and the support vector regression (SVR) nonlinear mapping model of the wheel-rail system was established. The learning, prediction, and verification were carried out. Finally, the reliable probability of the amplification coefficient distribution of the response index of the train and structure in different ranges was obtained based on the SVR nonlinear mapping model and Latin hypercube sampling method. The limit of the length of the mortar filling layer void was, thus, obtained. The results show that the SVR nonlinear mapping model developed in this paper has a high fitting accuracy of 0.993, and the computational efficiency is significantly improved by 99.86%. It can be used to calculate the dynamic response of the wheel-rail system. The length of the mortar filling layer void significantly affects the wheel-rail vertical force, wheel weight load reduction ratio, rail vertical displacement, and track plate vertical displacement. The dynamic response of the track structure has a more significant effect on the limit value of the length of the mortar filling layer void than the dynamic response of the vehicle, and the rail vertical displacement is the most obvious. At 250 km/h - 350 km/h train running speed, the limit values of grade I, II, and III of the lengths of the mortar filling layer void are 3.932 m, 4.337 m, and 4.766 m, respectively. The results can provide some reference for the long-term service performance reliability of the ballastless track-bridge system of HRS.

Assessment of the Impact Factor and the Stress Histogram of Railway Bridges in Korea (국내 강철도 교량의 충격계수 및 응력빈도분포의 평가)

  • Choi, Jun Hyeok;Cho, Sun Kyu;Chang, Dong Il
    • Journal of Korean Society of Steel Construction
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    • v.9 no.4 s.33
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    • pp.489-500
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    • 1997
  • The number of railway bridges in Korea reaches to about 3,000. Among them, the ratio of steel bridges is about 47%. Most of the long span railway bridges take the truss type, its number is 15 in Korea. These bridges have more than 30 years service life, it is expected that the damages of cracks and corrosion is going. Therefore, the estimation of fatigue life with random stress is considered as significant subject in maintenance. In this paper, the random stress was measured in bridges and counted the stress cycles using the rainflow counting method So, the stress range frequencies and their equivalent stress are obtained and the amplification factor for the span length, bridge types and traveling speed is assessed by the dynamic testing. From the results, the stress range of the stringer and the lower chord is higher than the other members and the characteristics of the stress histogram is varied to the loading system and the amount of the passing through trains. And the impact effects are depended on the traveling speed as well as the span length.

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MicroRNA-214 Regulates the Acquired Resistance to Gefitinib via the PTEN/AKT Pathway in EGFR-mutant Cell Lines

  • Wang, Yong-Sheng;Wang, Yin-Hua;Xia, Hong-Ping;Zhou, Song-Wen;Schmid-Bindert, Gerald;Zhou, Cai-Cun
    • Asian Pacific Journal of Cancer Prevention
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    • v.13 no.1
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    • pp.255-260
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    • 2012
  • Patients with non-small cell lung cancer (NSCLC) who have activating epidermal growth factor receptor (EGFR) mutations derive clinical benefit from treatment with EGFR-tyrosine kinase inhibitors ((EGFR-TKIs)-namely gefitinib and erlotinib. However, these patients eventually develop resistance to EGFR-TKIs. Despite the fact that this acquired resistance may be the result of a secondary mutation in the EGFR gene, such as T790M or amplification of the MET proto-oncogene, there are other mechanisms which need to be explored. MicroRNAs (miRs) are a class of small non-coding RNAs that play pivotal roles in tumorigenesis, tumor progression and chemo-resistance. In this study, we firstly successfully established a gefitinib resistant cell line-HCC827/GR, by exposing normal HCC827 cells (an NSCLC cell line with a 746E-750A in-frame deletion of EGFR gene) to increasing concentrations of gefitinib. Then, we found that miR-214 was significantly up-regulated in HCC827/GR. We also showed that miR-214 and PTEN were inversely expressed in HCC827/GR. Knockdown of miR-214 altered the expression of PTEN and p-AKT and re-sensitized HCC827/GR to gefitinib. Taken together, miR-214 may regulate the acquired resistance to gefitinib in HCC827 via PTEN/AKT signaling pathway. Suppression of miR-214 may thus reverse the acquired resistance to EGFR-TKIs therapy.

Construction of a Recombinant Leuconostoc mesenteroides CJNU 0147 Producing 1,4-Dihydroxy-2-Naphthoic Acid, a Bifidogenic Growth Factor

  • Eom, Ji-Eun;Moon, Gi-Seong
    • Food Science of Animal Resources
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    • v.35 no.6
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    • pp.867-873
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    • 2015
  • 1,4-Dihydroxy-2-naphthoic acid (DHNA), a precursor of menaquinone (vitamin K2), has an effect on growth stimulation of bifidobacteria and prevention of osteoporosis, making it a promising functional food material. Therefore, we tried to clone the menB gene encoding DHNA synthase from Leuconostoc mesenteroides CJNU 0147. Based on the genome sequence of Leu. mesenteroides ATCC 8293 (GenBank accession no., CP000414), a primer set (Leu_menBfull_F and Leu_menBfull_R) was designed for the PCR amplification of menB gene of CJNU 0147. A DNA fragment (1,190 bp), including the menB gene, was amplified, cloned into pGEM-T Easy vector, and sequenced. The deduced amino acid sequence of MenB (DHNA synthase) protein of CJNU 0147 had a 98% similarity to the corresponding protein of ATCC 8293. The menB gene was subcloned into pCW4, a lactic acid bacteria - E. coli shuttle vector, and transferred to CJNU 0147. The transcription of menB gene of CJNU 0147 (pCW4::menB) was increased, when compared with those of CJNU 0147 (pCW4) and CJNU 0147 (−). The DHNA was produced from it at a detectable level, indicating that the cloned menB gene of CJNU 0147 encoded a DHNA synthase which is responsible for the production of DHNA, resulting in an increase of bifidogenic growth stimulation activity.

Evaluation of Liquefaction Potential for Marine Silty Sand Deposits during Earthquake (서해안 사질토지반의 지진시 액상화 예측)

  • 이희명;정두영
    • Journal of Korean Society of Coastal and Ocean Engineers
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    • v.6 no.1
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    • pp.23-33
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    • 1994
  • Liquefaction characteristics of the reclaimed marine sand deposits is studied by means of the dynamic response analysis and the cyclic triaxial compression test. 1) From the result of the dynamic response analysis. it was found that the amplification of ground surface maximum acceleration varied with input earthquake motions and soil data, and earthquake coefficients were proposed to be applicable in evaluating liquefaction potential by simplified prediction methods. 2) For upper and soft sand deposits with small N-value, liquefaction strengths estimated by Seed and Idriss's simplified method were lower than those by the cyclic triaxial test while those by Iwasaki & Tatsuoka's or Vs-method were not lower. 3) Simplified methods were inclined to overestimate liquefaction potential in comparison with the dynamic response analysis and the cyclic triaxial compression test Allowable depths of liquefaction(safety factor 1) were estimated to be 7-14m for 0.1 -0.2g of input maximum acceleration.

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The Virulence Factors of Vibrio spp. (비브리오의 병원성 인자에 관한 연구)

  • Oh, Yang-Hyo;Kim, Yung-Bu;Park, Young-Min;Kim, Min-Jung;Cha, Mi-Sun;Kim, Young-Hee;Lim, Eun-Gyoung
    • The Journal of the Korean Society for Microbiology
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    • v.34 no.6
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    • pp.513-518
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    • 1999
  • A total of 113 Vibrio sp. strains were examined for plasmid content which were subjected to digestion with restriction enzymes. About the 55% Vibrio spp. have the plasmid more than one. Most of these plasmid various derivatives ranged from $2.4\;kb{\sim}23\;kb$, especially two strains of V. mimicus and one strain of V. furnissii carried one high-molecular weight plasmid (molecular weight ranging between $70\;kb{\sim}100\;kb$). Results of restriction analysis for plasmid of this three strains were by no means the rule. For detection of tdh and ctx gene, the virulence factor involved in the pathogenesis, we carried out the TDH and CT assay, PCR amplification, and hybridization. A total 11 strains were produced TDH, involved in 9 strains of V. parahaemolyticus and 1 strain of V. alginolyticus from clinical isolates and 1 strains of V. mimicus from environmental isolates. In the experiments of tdh gene detection, in all, 3 strains of V. parahaemolyticus from clinical isolates and 2 strains from environmental isolates could be successfully amplified in 400 bp by PCR. The PCR results were consistent with DNA hybridization tests. In the experiments of CT assay, in all, 3 strains of V. cholerae from clinical isolate and 1 strain of V. cholerae from environmental isolates were observed CT-producing. These CT-producing strains amplified in 302 bp by PCR for the detection of ctx gene. All CT-producing strains hybridized with digoxigenin-labeled DNA probe, while CT-negative strains did not hybridize. Also hybridization tests results for detection of ctx gene consistent with PCR.

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