• Title/Summary/Keyword: Damage Signal

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Inhibition of DNA-dependent Protein Kinase by Blocking Interaction between Ku Complex and Catalytic Subunit of DNA-dependent Protein Kinase

  • Kim, Chung-Hui;Cuong, Dang-Van;Kim, Jong-Su;Kim, Na-Ri;Kim, Eui-Yong;Han, Jin
    • The Korean Journal of Physiology and Pharmacology
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    • v.7 no.1
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    • pp.9-14
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    • 2003
  • Recent studies indicated that cancer cells become resistant to ionizing radiation (IR) and chemotherapy drugs by enhanced DNA repair of the lesions. Therefore, it is expected to increase the killing of cancer cells and reduce drug resistance by inhibiting DNA repair pathways that tumor cells rely on to escape chemotherapy. There are a number of key human DNA repair pathways which depend on multimeric polypeptide activities. For example, Ku heterodimer regulatory DNA binding subunits (Ku70/Ku80) on binding to double strand DNA breaks (DSBs) are able to interact with 470-kDa DNA-dependent protein kinase catalytic subunit (DNA-PKcs), and are essential for DNA-dependent protein kinase (DNA-PK) activity. It has been known that DNA-PK is an important factor for DNA repair and also is a sensor-transmitting damage signal to downstream targets, leading to cell cycles arrest. Our ultimate goal is to develop a treatment of breast tumors by targeting proteins involved in damage-signaling pathway and/or DNA repair. This would greatly facilitate tumor cell cytotoxic activity and programmed cell death through DNA damaging drug treatment. Therefore, we designed a domain of Ku80 mutants that binds to Ku70 but not DNA end binding activity and used the peptide in co-therapy strategy to see whether the targeted inhibition of DNA-PK activity sensitized breast cancer cells to irradiation or chemotherapy drug. We observed that the synthesized peptide (HNI-38) prevented DNA-PKcs from binding to Ku70/Ku80, thus resulting in inactivation of DNA-PK activity. Consequently, the peptide treated cells exhibited poor to no DNA repair, and became highly sensitive to IR or chemotherapy drugs, and the growth of breast cancer cells was inhibited. Additionally, the results obtained in the present study also support the physiological role of resistance of cancer cells to IR or chemotherapy.

Antimelanogenesis and skin-protective activities of Panax ginseng calyx ethanol extract

  • Lee, Jeong-Oog;Kim, Eunji;Kim, Ji Hye;Hong, Yo Han;Kim, Han Gyung;Jeong, Deok;Kim, Juewon;Kim, Su Hwan;Park, Chanwoong;Seo, Dae Bang;Son, Young-Jin;Han, Sang Yun;Cho, Jae Youl
    • Journal of Ginseng Research
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    • v.42 no.3
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    • pp.389-399
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    • 2018
  • Background: The antioxidant effects of Panax ginseng have been reported in several articles; however, little is known about the antimelanogenesis effect, skin-protective effect, and cellular mechanism of Panax ginseng, especially of P. ginseng calyx. To understand how an ethanol extract of P. ginseng berry calyx (Pg-C-EE) exerts skin-protective effects, we studied its activities in activated melanocytes and reactive oxygen species (ROS)-induced keratinocytes. Methods: To confirm the antimelanogenesis effect of Pg-C-EE, we analyzed melanin synthesis and secretion and messenger RNA and protein expression levels of related genes. Ultraviolet B (UVB) and hydrogen peroxide ($H_2O_2$) were used to induce cell damage by ROS generation. To examine whether this damage is inhibited by Pg-C-EE, we performed cell viability assays and gene expression and transcriptional activation analyses. Results: Pg-C-EE inhibited melanin synthesis and secretion by blocking activator protein 1 regulatory enzymes such as p38, extracellular signal-regulated kinases (ERKs), and cyclic adenosine mono-phosphate response element-binding protein. Pg-C-EE also suppressed ROS generation induced by $H_2O_2$ and UVB. Treatment with Pg-C-EE decreased the expression of matrix metalloproteinases, mitogen-activated protein kinases, and hyaluronidases and increased the cell survival rate. Conclusion: These results suggest that Pg-C-EE may have antimelanogenesis properties and skin-protective properties through regulation of activator protein 1 and cyclic adenosine monophosphate response element-binding protein signaling. Pg-C-EE may be used as a skin-improving agent, with moisture retention and whitening effects.

A Study on the Effect of Liriopis tuber water extract on Hydrogen Peroxide-stimulated C6 Astrocyte Cells (과산화수소 자극으로 활성화된 C6 성상교세포에 대한 맥문동추출물의 조절 효능 연구)

  • Park, Ki Ho;Kang, Seok Yong;Jung, Hyo Won;Park, Yong-Ki
    • The Korea Journal of Herbology
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    • v.35 no.4
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    • pp.9-16
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    • 2020
  • Objective : To identify the effects of the water extract of Liriope platyphylla tuber (Liriopis tuber, LT) on the activation of astocytes, we investigated the regulatory effects of LT extract on H2O2-induced oxidative damage in C6 rat astrocytes. Methods : LT extract was extracted with boiling water. C6 cell line were treated with LT extract at 1, 2, and 3 mg/㎖ or without for 30 min and then stimulated with H2O2 at 5 ㎛ for 24 hr. The cell viability was measured by MTT assay. The expression of glial fibrillary acidic protein (GFAP), signal transducer and activator of transcription 3 (STAT3), phospho-STAT3 (pSTAT3), cyclooxygenase (COX-2), Nuclear factor-κB (NF-κB), superoxide dismutase 2 (SOD2), heme oxygenase-1 (HO-1), catalase, Akt, phospho-Akt (p-Akt) phosphoinositide 3-kinases (PI3K), and protein kinase C alpha (PKCα) proteins were determined by Western blot, respectively. GFAP expression was also observed with immunocytochemistry under a fluorescence microscope. Results : LT extract induced cell proliferation in H2O2-stimulated C6 cells. LT extract significantly inhibited the expression of GFAP, NF-κB and COX-2 and increased the expression of HO-1 and the phosphorylation of STAT3 in H2O2-stimulated C6 cells. LT extract also significantly increased the phosphorylation of Akt and decreased the expression of PKCα in a dose-dependent manner in H2O2-stimulated C6 cells. Conclusions : LT extract can regulate H2O2-induced activation of astrocytes through inhibiting the expression of NF-κB, COX-2 and regulating Akt / HO-1, STAT3 or PKCα signaling pathway.

Estimation of Allowable Drop Height for Oriental Pears by Impact Tests (충격시험에 따른 배의 허용낙하높이 추정)

  • Kim, M. S.;Jung, H. M.;Seo, R.;Park, I. K.;Hwang, Y. S.
    • Journal of Biosystems Engineering
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    • v.26 no.5
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    • pp.461-468
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    • 2001
  • Impact between fruits and other materials is a major cause of product damage in harvesting and handling systems. The oriental pears are more susceptible to bruising than other fruits such as European pears and apples, and are required more careful handling. The interest in the handling of the pears for the processing systems has raised the question of the allowable drop height to which pears can be dropped without causing objectionable damage. Drop tests on pears were conducted using an impact device developed by authors to estimate the allowable drop height without bruising. The impact device was constructed to hold in a selected orientation and to release a fruit by vacuum for dropping on to a force transducer. The drop height was adjustable for zero to 60 cm to achieve the desired distance between the bottom of the fruits and the top of the impact force transducer. The transducer was secured to 150 kg$\sub$f/ concrete block. The transducer signal was sampled every 0.17 ms with a strain gage measurement board in the micro computer where it was digitaly stored for later analysis. The selected sample fruit was Niitaka cultivar of pears which is one of the most promising fruit for export in Korea. The pears were harvested during the 1998 harvest season from an orchard in Daejeon. The sample fruit was selected from two groups which were stored for 3 months and 5 months respectively by the method of current commercial practice. The pears were allowed to stabilize at environmental condition(18$^{\circ}C$, 65% rh) of the experimental room. One hundred fifty six pears were tested from the heights of 5, 7.5. 10 and 12.5 cm while measurement were made of impact peak force, contact time, time to peak force, dwell time, pear diameter and mass. The bioyield strength and modulus of elasticity were measured using UTM immediately after each drop test. The allowable drop height was estimated on the base of bioyield strength of the pears in two ways. One was assumed the peak force during impact test increasing linearly with time, and the other was based on the actual drop test results. The computer program was developed for measuring the impact characteristics of the pears and analyzing the data obtained in the study. The peak force increased while contact times decreased with increasing drop height and contact times of the sample from the hard tissue group. The allowable drop height increased with increasing bioyield strength and contact times, and also varied with Poisson\`s ratio, mass and equilibrium radius of the pears. The allowable drop height calculated by a theoretical method was in the range from 1 to 4 cm, meanwhile, the estimated drop height considering the result of the impact test was in the range from 1 to 6 cm. Since the physical properties of fruits affected significantly the allowable drop height, the physical properties of the fruits should be considered when estimating the allowable drop height.

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Analysis of acoustic emission parameters according to failure of rock specimens (암석시편 파괴에 따른 acoustic emission 특성인자 분석)

  • Lee, Jong-Won;Oh, Tae-Min;Kim, Hyunwoo;Kim, Min-Jun;Song, Ki-Il
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.21 no.5
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    • pp.657-673
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    • 2019
  • A monitoring method based on acoustic emission (AE) sensor has been widely used to evaluate the damage of structures in underground rock. The acoustic emission signal generated from cracking in material is analyzed as various acoustic emission parameters in time and frequency domain. To investigate from initial crack generation to final failure of rock material, it is important to understand the characteristics of acoustic emission parameters according to the stress ratio and rock strength. In this study, uniaxial compression tests were performed using very strong and weak rock specimen in order to investigate the acoustic emission parameters when the failure of specimen occurred. In the results of experimental tests, the event, root-mean-square (RMS) voltage, amplitude, and absolute energy of very strong rock specimen were larger than those of the weak rock specimen with an increase of stress ratio. In addition, the acoustic emission parameters related in frequency were more affected by specification (e.g., operation and resonant frequency) of sensors than the stress ratio or rock strength. It is expected that this study may be meaningful for evaluating the damage of underground rock when the health monitoring based on the acoustic emission technique will be performed.

Second harmonic generation of pulsed corona - poled nonlinear optical polymer films (펄스 corona 배향된 비선형광학 고분자박막의 제2 고조파발생)

  • Kim, Jun-Soo;Lee, Jong-Ha;Lee, Hwang-Un;Kim, Sang-Youl;Won, Young-Hee
    • Korean Journal of Optics and Photonics
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    • v.13 no.4
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    • pp.356-362
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    • 2002
  • The molecular orientational dynamics of the nonlinear optical(NLO) side-chain polymer N-(4-nitrophenyl)-(L)-prolinol-poly (pphenylene terephthalates) have been studied using nonlinear optical responses as measured by second harmonic generation (SHG). A new pulsed corona poling is used to orient the NLO chromophores and the polymer segments into the noncentrosymmetric structure required to obtain the SHG signal. By corona poling of negative high voltage pulses with variable repetition rates (between 0.5 and 10 ㎑) at temperature between 25$^{\circ}C$ and 80$^{\circ}C$, well below and about the glass transition temperature 70$^{\circ}C$, the side-chain chromophores and the polymer chain contour rearrange themselves and create the domain structure observed by atomic force microscopy(AFM). The pulsed corona voltage enhances the orientational ordering of the NLO chromophores and also significantly influences the growth of SHG signal and the improved relaxation behavior after the poling field is removed, reducing the visible damage to the polymer film dramatically. This new pulsed corona poling experiment gave direct in situ evidence that the NLO chromophore and the polymer backbone undergo anisotropic rearrangement during the poling process.

Spectral Properties of the Sound From the Mechanical Valve Employed in an Implantable Biventricular Assist Device (이식형 양심실 보조 장치에 사용된 기계식 판막의 음향 스펙트럼 특성)

  • 최민주;이서우;이혁수;민병구
    • Journal of Biomedical Engineering Research
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    • v.22 no.5
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    • pp.439-448
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    • 2001
  • This paper considers the acoustical characteristics of the closing click sounds of the mechanical valves employed in an implantable biventricular assist device (BYAD) and their re1evance to the Physical states of the valved. Bj rk Shiley Convexo Concave tilting disk valve was chosen for the study and acoustic measurement was made for the BYAD operated in a mock circulatory system as well as implanted in an animal (sheep). In the BYAD operated in the mock circulatory system. three different states of the valve were examined, ie. normal. mechanically damaged. pseudo-thrombus attached. Microphone measurement for the BVAD implanted in the animal was carried out for five days at a regular time interval from one day after implantation. Characteristic spectrum of the sound from the valve was estimated using Multiple Signal Classification (MUSIC) in which the optimal order was determined according to Bayesian Information Criterion (BIC) . It was observed that the mechanical damage of the valve resulted in changes of the structure of the acoustic spectrum. In contrast. the thrombus formed on the valve did not change much the basic structure of the spectrum but brought about altering the spectral Peak frequencies and energies. Maximum spectral Peak (MSP) with the greatest energy was seen at 2 kHz for the normal valve and it was shifted to 3 kHz for the calve attaching the Pseudo-thrombus. Unlike the normal valve, strong spectral Peak appeared around 7 kHz in the sound from the valve mechanically damaged. In the case of the BYAD implanted in the animal. as the thrombus grew, acoustic energy was reduced relatively more in the low frequency components (〈 2 kHz) and the frequencies of the 1st, 2nd and 3rd MSP were increased little. The thrombus formation would result in reduction in both the variability of the 1st, 2nd and 3rd MSP and the value of the BIC optimal order.

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Quantitative EC Signal Analysis on the Axial Notch Cracks of the SG Tubes (SG Tube 축방향 노치 균열의 정량적 EC 신호평가)

  • Min, Kyong-Mahn;Park, Jung-Am;Shin, Ki-Seok;Kim, In-Chul
    • Journal of the Korean Society for Nondestructive Testing
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    • v.29 no.4
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    • pp.374-382
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    • 2009
  • Steam generator(SG) tube, as a barrier isolating primary to the secondary coolant system of nuclear power plants(NPP), must maintain the structural integrity far the public safety and its efficient power generation capacity. And SG tubes bearing defects must be timely detected and taken repair measures if needed. For the accomplishment of these objectives, SG tubes have been periodically examined by eddy current testing(ECT) on the basis of administrative notices and intensified SG management program(SGMP). Stress corrosion cracking(SCC) on the SG tubes is not easily detected and even missed since it has lower signal amplitude and other disturbing factors against its detection. However once SCC is developed, that can cause detrimental affects to the SG tubes due to its rapid propagation rate. Accordingly SCC is categorized as prime damage mechanism challenging the soundness of the SG tubes. In this study, reproduced EDM notch specimens are examined for the detectability and quantitative characterization of the axial ODSCC by +PT MRPC probe, containing pancake, +PT and shielded pancake coils apart in a single plane around the circumference. The results of this study are assumed to be applicable fur providing key information of engineering evaluation of SCC and improvement of confidence level of ECT on SG tubes.

Factors Influencing Crash Severity by the Types of Bus Transportation Services Using Ordered Probit Models (순서형 프로빗 모형을 이용한 버스 운송사업 유형 별 사고심각도 영향요인 분석)

  • YOON, Sangwon;KHO, Seung-Young;KIM, Dong-Kyu
    • Journal of Korean Society of Transportation
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    • v.36 no.1
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    • pp.13-22
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    • 2018
  • Buses, one of the representative public transportation modes, are divided into a vareity of service types according to the purpose of operation, operating distance, and management agencies. Although bus-involved crashes may cause large amount of damage due to the higher number of passengers boarded on a bus, prior research has little focused on crash severity according to bus service types. This study aims to investigate factors influencing crash severity in bus-involved crashes and to present policy implications to reduce crash severity by bus service type. To do this, bus-involved crash data from the Traffic Accident Analysis System (TAAS) during five-year period are used. Ordered probit models for three types of bus service, i.e., city bus, suburban and express buses, and charter buses, are estimated to analyze the factors of accident severity. The results show that there are significant differences of factors affecting crash severity among the types of bus services while speed and road surface influence all the types of buses. In case of local buses, time of day, roadway alignment, and installation of a traffic signal are found to be statistically significant factors. Seat belt and road class have significant effects on injury severity of the intercity and express buses. Chartered buses have time of day, driving experience, seatbelt, traffic signal, and day of week as the significant factors. The results of this study are expected to contribute to the reduction of the crash severity by each bus service type.

The Study on the digital conversion present situation and consideration regarding an issue of analogue cable broadcast (아날로그 케이블 방송의 디지털 전환 현황과 쟁점에 관한 고찰)

  • Kim, Hee-Kyung;Kim, Dug-Mo
    • Journal of Digital Convergence
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    • v.11 no.6
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    • pp.1-9
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    • 2013
  • The digital signal is terminated on Dec.31, 2012. But most of the analog cable subscribers are faced with the difficult reception of the digital because the government has defined the terrestrial broadcast as digital transition obligation operators. It is estimated that half analog of the total pay-TV subscriber that is approximately 10million households that are directly receiving terrestrial signal must hold the digital TV or DtoA convertor to transit digital. But cable system subscriber should buy Set-top box that are expensive and pay the expensive rates. The cast of analog cable subscribers has been classified as a group that can cause the most damage after digital switch. This study investigate the problem, and cause, solution of the analog cable subscribers that are placed in the blind spots of the digital switch.