• 제목/요약/키워드: Damage mechanism

검색결과 1,422건 처리시간 0.034초

Tumor suppressor Parkin induces p53-mediated cell cycle arrest in human lung and colorectal cancer cells

  • Byung Chul Jung;Sung Hoon Kim;Yoonjung Cho;Yoon Suk Kim
    • BMB Reports
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    • 제56권10호
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    • pp.557-562
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    • 2023
  • Dysregulation of the E3 ubiquitin ligase Parkin has been linked to various human cancers, indicating that Parkin is a tumor suppressor protein. However, the mechanisms of action of Parkin remain unclear to date. Thus, we aimed to elucidate the mechanisms of action of Parkin as a tumor suppressor in human lung and colorectal cancer cells. Results showed that Parkin overexpression reduced the viability of A549 human lung cancer cells by inducing G2/M cell cycle arrest. In addition, Parkin caused DNA damage and ATM (Ataxia telangiectasia mutated) activation, which subsequently led to p53 activation. It also induced the p53-mediated upregulation of p21 and downregulation of cyclin B1. Moreover, Parkin suppressed the proliferation of HCT-15 human colorectal cancer cells by a mechanism similar to that in A549 lung cancer cells. Taken together, our results suggest that the tumor-suppressive effects of Parkin on lung and colorectal cancer cells are mediated by DNA damage/p53 activation/cyclin B1 reduction/cell cycle arrest.

재생잔골재를 활용한 화재피해를 입은 콘크리트의 공학적 특성에 관한 실험적 연구 (An Experimental Study on the Engineering Properties of Deteriorated Concrete using Recycled Fine Aggregate by Fire Damage)

  • 권영진
    • 한국구조물진단유지관리공학회 논문집
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    • 제10권1호
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    • pp.190-196
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    • 2006
  • 기존 연구에서 살펴보면, 철근콘크리트구조물에 발생한 화재로 인해 경화된 시멘트 페이스트와 골재의 수축과 팽창의 차이에 따라 조직이 와해되고, 열응력에 의해 균열이 발생하여 내구성이 저하한다. 그래서 성능저하의 정확한 진단은 일반적인 콘크리트구조물에서 방화성능저하의 매커니즘에 관한 기초가 요구되며, 고온에 노출된 콘크리트의 특성에 대한 기초 정보와 데이터는 성능저하의 정확한 진단을 위해 필요하다. 따라서, 본 연구는 다양한 콘크리트 시험체를 제작하여, 고온 환경에서 노출시켜, 폭열을 관찰하고, 공학적인 특성을 평가함으로서 화재피해를 입은 콘크리트구조물 성능저하의 빠르고 정확한 진단을 위한 기초적인 데이터를 제공하고자 한다.

Application of a mesh-free method to modelling brittle fracture and fragmentation of a concrete column during projectile impact

  • Das, Raj;Cleary, Paul W.
    • Computers and Concrete
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    • 제16권6호
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    • pp.933-961
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    • 2015
  • Damage by high-speed impact fracture is a dominant mode of failure in several applications of concrete structures. Numerical modelling can play a crucial role in understanding and predicting complex fracture processes. The commonly used mesh-based Finite Element Method has difficulties in accurately modelling the high deformation and disintegration associated with fracture, as this often distorts the mesh. Even with careful re-meshing FEM often fails to handle extreme deformations and results in poor accuracy. Moreover, simulating the mechanism of fragmentation requires detachment of elements along their boundaries, and this needs a fine mesh to allow the natural propagation of damage/cracks. Smoothed Particle Hydrodynamics (SPH) is an alternative particle based (mesh-less) Lagrangian method that is particularly suitable for analysing fracture because of its capability to model large deformation and to track free surfaces generated due to fracturing. Here we demonstrate the capabilities of SPH for predicting brittle fracture by studying a slender concrete structure (column) under the impact of a high-speed projectile. To explore the effect of the projectile material behaviour on the fracture process, the projectile is assumed to be either perfectly-elastic or elastoplastic in two separate cases. The transient stress field and the resulting evolution of damage under impact are investigated. The nature of the collision and the constitutive behaviour are found to considerably affect the fracture process for the structure including the crack propagation rates, and the size and motion of the fragments. The progress of fracture is tracked by measuring the average damage level of the structure and the extent of energy dissipation, which depend strongly on the type of collision. The effect of fracture property (failure strain) of the concrete due to its various compositions is found to have a profound effect on the damage and fragmentation pattern of the structure.

Nitric Oxide-cGMP-Protein Kinase G Pathway Contributes to Cardioprotective Effects of ATP-Sensitive $K^+$ Channels in Rat Hearts

  • Cuong, Cang Van;Kim, Na-Ri;Cho, Hee-Cheol;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • 제8권2호
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    • pp.95-100
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    • 2004
  • Ischemic preconditioning (IPC) has been accepted as a heart protection phenomenon against ischemia and reperfusion (I/R) injury. The activation of ATP-sensitive potassium $(K_{ATP})$ channels and the release of myocardial nitric oxide (NO) induced by IPC were demonstrated as the triggers or mediators of IPC. A common action mechanism of NO is a direct or indirect increase in tissue cGMP content. Furthermore, cGMP has also been shown to contribute cardiac protective effect to reduce heart I/R-induced infarction. The present investigation tested the hypothesis that $K_{ATP}$ channels attenuate DNA strand breaks and oxidative damage in an in vitro model of I/R utilizing rat ventricular myocytes. We estimated DNA strand breaks and oxidative damage by mean of single cell gel electrophoresis with endonuclease III cutting sites (comet assay). In the I/R model, the level of DNA damage increased massively. Preconditioning with a single 5-min anoxia, diazoxide $(100\;{\mu}M)$, SNAP $(300\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate (8-pCPT-cGMP) $(100\;{\mu}M)$ followed by 15 min reoxygenation reduced DNA damage level against subsequent 30 min anoxia and 60 min reoxygenation. These protective effects were blocked by the concomitant presence of glibenclamide $(50\;{\mu}M)$, 5-hydroxydecanoate (5-HD) $(100\;{\mu}M)$ and 8-(4-Chlorophenylthio)-guanosine-3',5'-cyclic monophosphate, Rp-isomer (Rp-8-pCPT-cGMP) $(100\;{\mu}M)$. These results suggest that NO-cGMP-protein kinase G (PKG) pathway contributes to cardioprotective effect of $K_{ATP}$ channels in rat ventricular myocytes.

소풍보심탕이 고혈압, 혈전 및 뇌진탕에 미치는 영향 (Study on the Effect of Sopungbosim-tang on Hypertension, Thrombosis and Brain damage)

  • 배경일;김동희;이용구;김윤식;설인찬
    • 동의생리병리학회지
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    • 제16권2호
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    • pp.245-256
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    • 2002
  • This studt was investigated to prove the effect of SPBST on the hypertension, the thrombosis and the brain damage. The results were as follows; 1. SPBST affected the htpertension as adepressant, but insignificant. 2. SPBST decreased significantly dopamine, aldosterone but ineffective on the epinephrine, norepinephrine and renin activity. 3. SPBST increased the NO product but insignificant. 4. SPBST had a death suppression effect by 50% in pulmonary thrombosis inducement experiment and activated slightly on the fibrinolytic activity. 5. SPBST suppressed significantly platelet diminution and prolonged insignificantly PT and APTT. 6. On the measure of the blood flow rate induced by the thrombus, in vivo SPBST accelerated the blood flow rate, in vitro insignificant. 7. SPBST had no toxicity on the PC12 cell and B103 cell induced by amyloid β protein (-35) and a protective effect, in proportion to the density. 8. SPBST decreased significantly coma duration time in a Infatal dose of KCN and showed 50% of survival rate in a fatal dose. 9. SPBST decreased significantly ischemic area and edema incited by the MCA blood flow block. These results indicate that SPBST can be used in hypertension, the thrombosis, the brain damage, the ischemic cerebral infarction and the acute stage of the brain damage. Further study will be needed about the functional mechanism and etc.

와송약침액(瓦松藥鍼液)이 신장세포(腎臟細胞)에서 H2O2에 의한 세포사망(細胞死亡) 및 DNA 손상(損傷)에 미치는 영향(影響) (The Effects of Orostachys Japonicus A. Berger Aquacupuncture on Cell Death and DNA Damage Induced by H2O2 in Renal Tubular Cell)

  • 박상원;송춘호
    • Journal of Acupuncture Research
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    • 제18권1호
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    • pp.88-99
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    • 2001
  • Objectives : This study was performed to determine if Orostachys japonicus A. Berger aquacupuncture (OjB) provides the protective effect against the loss of celi viability and DNA damage induced by oxidant in renal proximal tubular cells. Methods : The cell viability was evaluated by a MTT reduction assay and DNA damage was estimated by measuring double stranded DNA breaks in opossum kidney (OK) cells, an established proximal tubular cell line. Lipid peroxidation was determined by measuring malondialdehyde (MDA), a product of lipid peroxidation. Results : $H_2O_2$ increased the loss of cell viability in a time-dependent manner, which were prevented by 0.1% OjB. The protective effect of OjB was dose-dependent over concentration range of 0.05-0.5%. $H_2O_2$ caused ATP depletion and DNA damage, which were prevented by OjB and the hydrogen peroxide scavenger catalase. The loss of cell viability by $H_2O_2$ was not affected by the antioxidant DPPD, but lipid peroxidation by the oxidant was completely inhibited by DPPD. Conclusions : These data suggest that $H_2O_2$-induced death results from a lipid peroxidation-independent mechanism and the protective effect of OjB is not associated with its antioxidant activity.

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Photochemical Property and Photodynamic Activity of Tetrakis(2-naphthyl) Porphyrin Phosphorus(V) Complex

  • Hirakawa, Kazutaka;Aoki, Shunsuke;Ueda, Hiroyuki;Ouyang, Dongyan;Okazaki, Shigetoshi
    • Rapid Communication in Photoscience
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    • 제4권2호
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    • pp.37-40
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    • 2015
  • To examine the photosensitized biomolecules damaging activity, dimethoxyP(V)tetrakis(2-naphthyl)porphyrin (NP) and dimethoxyP(V)tetraphenylporphyrin (PP) were synthesized. The naphthyl moiety of NP hardly deactivated the photoexcited P(V)porphyrin ring in ethanol. In aqueous solution, the naphthyl moiety showed the quenching effect on the photoexcited porphyrin ring, possibly through electron transfer and self-quenching by a molecular association. Binding interaction between human serum albumin (HSA), a water soluble protein, and these porphyrins could be confirmed by the absorption spectral change. The apparent association constant of NP was larger than that of PP. It is explained by that more hydrophobic NP can easily bind into the hydrophobic pockets of HSA. The photoexcited PP effectively induced damage of the tryptophan residue of HSA, through electron transfer-mediated oxidation and singlet oxygen generation. NP also induced HSA damage during photo-irradiation and the contributions of the electron transfer and singlet oxygen mechanisms were speculated. The electron transfer-mediated mechanism to the photosensitized protein damage should be advantageous for photodynamic therapy in hypoxic condition. The quantum yield of the HSA photodamage by PP was significantly larger than that of NP. The quenching effect of the naphthyl moiety is considered to suppress the photosensitized protein damage. In conclusion, the naphthalene substitution to the P(V)porphyrins can enhance the binding interaction with hydrophobic biomacromolecules such as protein, however, this substitution may reduce the photodynamic effect of P(V)porphyrin ring in aqueous media.

마코프 프로세스에 기반한 확률적 피해 파급 모델 (A Probabilistic Model of Damage Propagation based on the Markov Process)

  • 김영갑;백영교;인호;백두권
    • 한국정보과학회논문지:시스템및이론
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    • 제33권8호
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    • pp.524-535
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    • 2006
  • 급속한 인터넷 기술의 발전으로 기업이나 기관에서의 업무 처리는 인터넷 기반 기술에 의존하고 있다. 또한 주요 정보통신 시설의 네트워크 의존도와 결합도가 증가함에 따라 시스템내의 취약성을 대상으로 하는 침해 행위와 같은 사이버 보안 사고의 수가 크게 증가하고 있다. 이에 따라 개인정보는 물론 컴퓨터 자원들의 침해와 관련된 피해 파급 (damage propagation)에 관한 연구가 요구된다. 그러나 기존의 제안된 모델들은 위험 관리 측면의 방법론적인 접근이거나, 바이러스 (virus) 나 웹 (worm) 같은 특정 위협 (threats) 에 대해서만 적용할 수 있는 연구가 진행되어 왔다. 따라서 본 논문에서는 과거의 위협 발생 데이타를 근거로 하여 전체 시스템이 가지고 있는 다양한 위협들에 대해 적용 가능한 마코프 프로세스 (markov process) 에 기반한 피해 파급 모델을 제시한다. 이를 통하여 각 위협별 발생 확률 및 발생 빈도를 예측할 수 있다.

Damage assessment of buildings after 24 January 2020 Elazığ-Sivrice earthquake

  • Nemutlu, Omer Faruk;Balun, Bilal;Sari, Ali
    • Earthquakes and Structures
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    • 제20권3호
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    • pp.325-335
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    • 2021
  • The majority of Turkey's geography is at risk of earthquakes. Within the borders of Turkey, including the two major active faults contain the North-Eastern and Eastern Anatolia, earthquake, threatening the safety of life and property. On January 24, 2020, an earthquake of magnitude 6.8 occurred at 8:55 p.m. local time. According to the data obtained from the stations in the region, peak ground acceleration in the east-west direction was measured as 0.292 g from the 2308 coded station in Sivrice. It is thought that the earthquake with a magnitude of Mw 6.8 was developed on the Sivrice-Puturge segment of the Eastern Anatolian Fault, which is a left lateral strike slip fault, and the tear developed in an area of 50-55 km. Aftershocks ranging from 0.8 to 5.1 Mw occurred following the main shock on the Eastern Anatolian Fault. The earthquake caused severe structural damages in Elazığ and neighboring provinces. As a result of the field investigations carried out in this study, significant damage levels were observed in the buildings since it did not meet the criteria in the earthquake codes. Within the study's scope, the structural damage cases in reinforced concrete and masonry structures were investigated. Many structural deficiencies and mistakes such as non-ductile details, poor concrete quality, short columns, strong beams-weak columns mechanism, large and heavy overhangs, masonry building damages and inadequate reinforcement arrangements were observed. Requirements of seismic codes are discussed and compared with observed earthquake damage.

열차주행특성을 고려한 레일표면결함 분석 (Evaluation of Rail Surface Defects Considering Vehicle Running Characteristics)

  • 최정열
    • 문화기술의 융합
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    • 제10권3호
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    • pp.845-849
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    • 2024
  • 현재 도시철도 레일의 노후화로 인한 레일표면결함이 증가하고 있으나 국가에서 제정된 궤도성능평가에 관한 세부지침에서 레일표면손상을 기술자의 육안, 간단한 측정 도구로 점검을 수행하는 실정이다. 주기적인 선로순회작업 및 육안점검을 통해 레일표면의 결함을 발견하는 것은 매우 중요하다. 그러나 점검자의 주관적 판단에 의해 레일표면의 결함의 경중을 평가하는 것은 레일 내부의 손상을 예측하기에 상당한 제약이 따른다. 본 연구에서는 레일표면손상에 따른 레일내부 균열특성에 관한 연구로서 현장측정에서는 레일표면 손상개소를 선정하여 가속구간 및 제동구간의 노후레일 시료를 채취하여 레일표면손상 상태를 평가하고자 전자주사현미경(SEM)을 이용하여 균열특성을 분석하였다. 분석결과, 주행 중인 열차로 인해 발생하는 균열 메커니즘과 레일표면방향으로 올라오는 각도로 균열이 발생하는 가속구간의 균열특성을 실험적으로 입증하였다.