• Title/Summary/Keyword: PS-341

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PS-341-Induced Apoptosis is Related to JNK-Dependent Caspase 3 Activation and It is Negatively Regulated by PI3K/Akt-Mediated Inactivation of Glycogen Synthase Kinase-$3{\beta}$ in Lung Cancer Cells (폐암세포주에서 PS-341에 의한 아포프토시스에서 JNK와 GSK-$3{\beta}$의 역할 및 상호관련성)

  • Lee, Kyoung-Hee;Lee, Choon-Taek;Kim, Young Whan;Han, Sung Koo;Shim, Young-Soo;Yoo, Chul-Gyu
    • Tuberculosis and Respiratory Diseases
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    • v.57 no.5
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    • pp.449-460
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    • 2004
  • Background : PS-341 is a novel, highly selective and potent proteasome inhibitor, which showed cytotoxicity against some tumor cells. Its anti-tumor activity has been suggested to be associated with modulation of the expression of apoptosis-associated proteins, such as p53, $p21^{WAF/CIP1}$, $p27^{KIP1}$, NF-${\kappa}B$, Bax and Bcl-2. c-Jun N-terminal kinase (JNK) and glycogen synthase kinase-$3{\beta}$ (GSK-$3{\beta}$) are important modulators of apoptosis. However, their role in PS-341-induced apoptosis is unclear. This study was undertaken to elucidate the role of JNK and GSK-$3{\beta}$ in the PS-341-induced apoptosis in lung cancer cells. Method : NCI-H157 and A549 cells were used in the experiments. The cell viability was assayed using the MTT assay and apoptosis was evaluated by proteolysis of PARP. The JNK activity was measured by an in vitro immuno complex kinase assay and by phosphorylation of endogenous c-Jun. The protein expression was evaluated by Western blot analysis. Dominant negative JNK1 (DN-JNK1) and GSK-$3{\beta}$ were overexpressed using plasmid and adenovirus vectors, respectively. Result : PS-341 reduced the cell viability via apoptosis, activated JNK and increased the c-Jun expression. Blocking of the JNK activation by overexpression of DN-JNK1, or pretreatment with SP600125, suppressed the apoptosis induced by PS-341. The activation of caspase 3 was mediated by JNK activation. Blocking of the caspase 3 activation suppressed PS-341-induced apoptosis. PS-341 activated the phosphatidylinositol 3-kinase (PI3K)/Akt pathway, but its blockade enhanced the PS-341-induced cell death via apoptosis. GSK-$3{\beta}$ was inactivated by PS-341 via the PI3K/Akt pathway. Overexpression of constitutively active GSK-$3{\beta}$ enhanced PS-341-induced apoptosis; in contrast, this was suppressed by dominant negative GSK-$3{\beta}$ (DN-GSK-$3{\beta}$). Inactivation of GSK-$3{\beta}$ by pretreatment with lithium chloride or the overexpression of DN-GSK-$3{\beta}$ suppressed both the JNK activation and c-Jun up-regulation induced by PS-341. Conclusion : The JNK/caspase pathway is involved in PS-341-induced apoptosis, which is negatively regulated by the PI3K/Akt-mediated inactivation of GSK-$3{\beta}$ in lung cancer cells.

Experimental study on component performance in steel plate shear wall with self-centering braces

  • Liu, Jia-Lin;Xu, Long-He;Li, Zhong-Xian
    • Steel and Composite Structures
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    • v.37 no.3
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    • pp.341-351
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    • 2020
  • Steel plate shear wall with self-centering energy dissipation braces (SPSW-SCEDB) is a lateral force-resisting system that exhibits flag-shaped hysteretic responses, which consists of two pre-pressed spring self-centering energy dissipation (PS-SCED) braces and a wall plate connected to horizontal boundary elements only. The present study conducted a series of cyclic tests to study the hysteretic performances of braces in SPSW-SCEDB and the effects of braces on the overall hysteretic characteristics of this system. The SPSW-SCEDB with PS-SCED braces only exhibits excellent self-centering capability and the energy loss caused by the large inclination angle of PS-SCED braces can be compensated by appropriately increasing the friction force. Under the combined effect of the two components, the SPSW-SCEDB exhibits a flag-shaped hysteretic response with large lateral resistance, good energy dissipation and self-centering capabilities. In addition, the wall plate is the primary energy dissipation component and the PS-SCED braces provide supplementary energy dissipation for system. The PS-SCED braces can provide up to 90% self-centering capability for the SPSW-SCEDB system. The compressive bearing capacity of the wall plate should be smaller than the horizontal remaining restoring force of the braces to achieve better self-centering effect of the system.

The Design of a 0.15 ps High Resolution Time-to-Digital Converter

  • Lee, Jongsuk;Moon, Yong
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.15 no.3
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    • pp.334-341
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    • 2015
  • This research outlines the design of a HR-TDC (High Resolution Time-to-Digital Converter) for high data rate communication systems using a $0.18{\mu}m$ CMOS process. The coarse-fine architecture has been adopted to improve the resolution of the TDC. A two-stage vernier time amplifier (2S-VTA) was used to amplify the time residue, and the gain of the 2S-VTA was larger than 64. The error during time amplification was compensated using two FTDCs (Fine-TDC) with their outputs. The resolution of the HR-TDC was 0.15 ps with a 12-bit output and the power consumption was 4.32 mW with a 1.8-V supply voltage.

Analysis of VOCs produced from incineration of Plastic Waste (플라스틱류 소각시 발생하는 VOCs 농도분석 연구)

  • 이병규;조정범
    • Proceedings of the Korea Air Pollution Research Association Conference
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    • 2000.11a
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    • pp.341-342
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    • 2000
  • 산업사회를 발전시키는데 있어서 큰 기여를 하여온 플라스틱(Plastic)은 사용의 편리성과 다양한 형태로의 제품의 증가, 최근 자동차수의 급격한 증가, 그리고 석유화학공업의 발달로 폐플라스틱류의 발생빈도와 함유량이 급증하고 있다. 일반적으로 널리 사용되어 지고 있는 플라스틱의 종류는 7대 범용수지로 분류되는 LDPE, HDPE, PP, PS, PVC, ABS, PET가 전체 플라스틱 생산의 대부분을 차지하고 있다. (중략)

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The Mechanism of Proteasome Inhibitor-Induced Apoptosis in Lung Cancer Cells (폐암 세포에서 Proteasome Inhibitor에 의한 Apoptosis의 기전)

  • Kim, Cheol Hyeon;Lee, Kyoung-Hee;Lee, Choon-Taek;Kim, Young Whan;Han, Sung Koo;Shim, Young Soo;Yoo, Chul Gyu
    • Tuberculosis and Respiratory Diseases
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    • v.54 no.4
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    • pp.403-414
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    • 2003
  • Background : Proteasome inhibitors can promote either cell survival or programmed cell death, depending on both the specific type and proliferative status of the cell. However, it is not well known whether inhibition of proteasome activity is related to apoptosis in lung cancer cells. In addition, the exact mechanisms responsible for apoptosis induced by proteasome inhibition are not well understood. In the present study, we have examined the effect of proteasome inhibition on lung cancer cells and tried to test the mechanisms that may be associated with the apoptosis of these cells. Methods : We examined the effect of proteasome inhibition with MG132 or PS-341 on cell survival in A549 and NCI-H157 lung cancer cells using MTT assay, and analyzed the cleavage of PARP by Western blot analysis to find evidence of apoptosis. Next, we evaluated the activation of caspase 3 by Western blot analysis and the activity of JNK by immunocomplex kinase assay. We also examined the changes in anti-apoptotic pathways like ERK and cIAP1 by Western blot analysis after inhibition of proteasome function. Results : We demonstrated that MG132 reduced cell survival by inducing apoptosis in A549 and NCI-H157 cells. Proteasome inhibition with MG132 or PS-341 was associated with activation of caspase 3 and JNK, reduced expression of activated ERK, and downregulation of cIAP1. Conclusion : Apoptosis induced by proteasome inhibition may be associated with the activation of pro-apoptotic pathways like caspase 3 and JNK and the inactivation of anti-apoptotic pathways in lung cancer cells.

A Stress Transfer Length of Pre-tensioned Members Using Ultra High Performance Concrete (초고성능 콘크리트 프리텐션부재의 응력전달길이)

  • Kim, Jee-Sang;Choi, Dong-Hun
    • Journal of the Korean Recycled Construction Resources Institute
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    • v.6 no.4
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    • pp.336-341
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    • 2018
  • The prestressing force introduced to the tendon in pretensioned concrete members is transferred by direct bond between tendon and concrete, which requires a proper estimation of stress transfer length. The use of pretensiond and/or precast members with UHPC (Ultra High Performance Concrete) may give many advantages in quality control. This paper presents an experiment to estimate the stress transfer length of UHPC for various compressive strength levels of UHPC, cover depths, diameters of tendons and tensioning forces. According to the result of this experiment, the stress transfer length of UHPC member is much reduced comparing that of normal strength concrete. The reduction in stress transfer length of UHPC may come from the high bond strength capacity of UHPC. The transfer lengths obtained from this experiment are compared to those in current design code and a new formula is proposed.

Determination Factors Affecting the High Order Aberrations in Preoperative and Postoperative LASEK (라섹 수술 전과 후의 고위수차에 영향을 미치는 결정변수)

  • Kim, Tae-Heung;Lee, Hyun;Rhee, Kang-Oh;Lee, Tae-Yong
    • Journal of the Korea Academia-Industrial cooperation Society
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    • v.15 no.9
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    • pp.5621-5627
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    • 2014
  • To specify the standard of LASEK surgery, this study examined the determination factors affecting the high order aberrations (HOAs) in preoperative and postoperative LASEK. 51 adult patients (102 eyes) were evaluated at the baseline and 2 months after LASEK surgery from Nov 2011 to Jul 2012. The postoperative HOAs ($0.538{\mu}m$) were higher than the preoperative ($0.341{\mu}m$). In linear regression analysis, the refractive components that affected the postoperative HOAs were $J_0$ of corneal astigmatism (CA, 0.400), $J_0$ of refractive astigmatism (RA, 0.389), corneal astigmatism (CA, 0.282), spherical equivalent (SE, 0.239), refractive astigmatism (RA, 0.213), and pupil size (PS, 0.194) with a high R. In multiple regression, $J_0$ of CA, PS and SE were significant factors with the postoperative HOAs. In conclusion, both HOAs and $J_0$ of CA should be considered when determining the suitable factors for LASEK surgery.

Development of a Nutrient Solution for Potato (Solanum tuberosum L.) Seed Tuber Production in a Closed Hydroponic System (수경재배용 감자 배양액 개발)

  • Chang, Dong-Chil;Kim, Sung-Yeul;Shin, Kwan-Yong;Cho, Young-Ryul;Lee, Yong-Beom
    • Horticultural Science & Technology
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    • v.18 no.3
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    • pp.334-341
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    • 2000
  • To develop a nutrient solution for a closed hydroponic system in potato (Solanum tuberosum L.) 'Atlantic' and 'Superior' potatoes were grown with the nutrient solutions whose strengths were 0.25, 0.5, 1.0, and 1.5 of the concentration of the nutrient solution developed by the National Horticultural Experiment Station in Japan. The best results in potato growth and yield were obtained with 0.5 and 1.0 strength nutrient solutions, and nutrient compositions for potato were determined based on the 1.0 strength nutrient solution; $14.4me{\cdot}L^{-1}\;N,\;4.2me{\cdot}L^{-1}\;P,\;7.5me{\cdot}L^{-1}\;K,\;5.5me{\cdot}L^{-1}\;Ca$, and $3.5me{\cdot}L^{-1}\;Mg$ for stolon growth stage and $14.8me{\cdot}L^{-1}\;N,\;4.0me{\cdot}L^{-1}\;P,\;8.5me{\cdot}L^{-1}\;K,\;6.5me{\cdot}L^{-1}\;Ca$, and $3.0me{\cdot}L^{-1}\;Mg$ for tuber growth stage. To examine the suitability of the nutrient solutions developed for potato, the strengths of 1.0 (PS 1.0S), 0.75 (PS 0.75S), or 0.5 (PS 0.5S) were compared with half-strength of Japanese Horticultural Experiment Station' solution (JH 0.5S). Changes in pH, EC, and mineral concentrations in nutrient solutions depended more on solution strength and growth stage than on the type of nutrient solution. However, most elements in solution remained constant with plant age in PS 0.75S solution during stolon growth stage, and in PS 0.5S solution during tuber growth stage. The greatest growth and tuber yield was obtained in the standard strength solution (PS 1.0S), and potato solution developed in this experiment was recommended for hydroponic culture of potato in a closed system.

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Proteasome Inhibitor-Induced IκB/NF-κB Activation is Mediated by Nrf2-Dependent Light Chain 3B Induction in Lung Cancer Cells

  • Lee, Kyoung-Hee;Lee, Jungsil;Woo, Jisu;Lee, Chang-Hoon;Yoo, Chul-Gyu
    • Molecules and Cells
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    • v.41 no.12
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    • pp.1008-1015
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    • 2018
  • $I{\kappa}B$, a cytoplasmic inhibitor of nuclear factor-${\kappa}B$ ($NF-{\kappa}B$), is reportedly degraded via the proteasome. However, we recently found that long-term incubation with proteasome inhibitors (PIs) such as PS-341 or MG132 induces $I{\kappa}B{\alpha}$ degradation via an alternative pathway, lysosome, which results in $NF-{\kappa}B$ activation and confers resistance to PI-induced lung cancer cell death. To enhance the anti-cancer efficacy of PIs, elucidation of the regulatory mechanism of PI-induced $I{\kappa}B{\alpha}$ degradation is necessary. Here, we demonstrated that PI up-regulates nuclear factor (erythroid-derived 2)-like 2 (Nrf2) via both de novo protein synthesis and Kelch-like ECH-associated protein 1 (KEAP1) degradation, which is responsible for $I{\kappa}B{\alpha}$ degradation via macroautophagy activation. PIs increased the protein level of light chain 3B (LC3B, macroautophagy marker), but not lysosome-associated membrane protein 2a (Lamp2a, the receptor for chaperone-mediated autophagy) in NCI-H157 and A549 lung cancer cells. Pretreatment with macroautophagy inhibitor or knock-down of LC3B blocked PI-induced $I{\kappa}B{\alpha}$ degradation. PIs up-regulated Nrf2 by increasing its transcription and mediating degradation of KEAP1 (cytoplasmic inhibitor of Nrf2). Overexpression of dominant-negative Nrf2, which lacks an N-terminal transactivating domain, or knock-down of Nrf2 suppressed PI-induced LC3B protein expression and subsequent $I{\kappa}B{\alpha}$ degradation. Thus, blocking of the Nrf2 pathway enhanced PI-induced cell death. These findings suggest that Nrf2-driven induction of LC3B plays an essential role in PI-induced activation of the $I{\kappa}B$/$NF-{\kappa}B$ pathway, which attenuates the anti-tumor efficacy of PIs.