The $Na^+/H^+$ exchanger is responsible for maintaining the acidic tumor microenvironment through its promotion of the reabsorption of extracellular $Na^+$ and the extrusion of intracellular $H^+$. The resultant increase in the extracellular acidity contributes to the chemoresistance of malignant tumors. In this study, the chemosensitizing effects of cariporide, a potent $Na^+/H^+-exchange$ inhibitor, were evaluated in human malignant mesothelioma H-2452 cells preadapted with lactic acid. A higher basal level of phosphorylated (p)-AKT protein was found in the acid-tolerable H-2452AcT cells compared with their parental acid-sensitive H-2452 cells. When introduced in H-2452AcT cells with a concentration that shows only a slight toxicity in H-2452 cells, cariporide exhibited growth-suppressive and apoptosis-promoting activities, as demonstrated by an increase in the cells with pyknotic and fragmented nuclei, annexin V-PE(+) staining, a $sub-G_0/G_1$ peak, and a $G_2/M$ phase-transition delay in the cell cycle. Preceding these changes, a cariporide-induced p-AKT down-regulation, a p53 up-regulation, an ROS accumulation, and the depolarization of the mitochondrial-membrane potential were observed. A pretreatment with the phosphatidylinositol-3-kinase (PI3K) inhibitor LY294002 markedly augmented the DNA damage caused by the cariporide, as indicated by a much greater extent of comet tails and a tail moment with increased levels of the p-histone H2A.X, $p-ATM^{Ser1981}$, $p-ATR^{Ser428}$, $p-CHK1^{Ser345}$, and $p-CHK2^{Thr68}$, as well as a series of pro-apoptotic events. The data suggest that an inhibition of the PI3K/AKT signaling is necessary to enhance the cytotoxicity toward the acidtolerable H-2452AcT cells, and it underlines the significance of proton-pump targeting as a potential therapeutic strategy to overcome the acidic-microenvironment-associated chemotherapeutic resistance.
Kim, Sang-Young;Woo, Dong-Cheol;Bang, Eun-Jung;Kim, Sang-Soo;Lim, Hyang-Sook;Choi, Chi-Bong;Choe, Bo-Young
Journal of the Korean Magnetic Resonance Society
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v.12
no.1
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pp.14-25
/
2008
To investigate the 3-bond connectivity of human brain metabolites by scalar coupling interaction through 2D-correlation spectroscopy (COSY) techniques using high field NMR spectroscopy. All NMR experiments were performed at 298K on Unity Inova 500 or 600 (Varian Inc.) equipped with a triple resonance probe head with z-shield gradient. Human brain metabolites were prepared with 10% $D_2O$. Two dimensional 2D COSY spectra were acquired with 4096 complex data points in $t_2$ and 128 or 256 increments in $t_1$ dimension. The spectral width was 9615.4 Hz and solvent suppression was achieved using presaturation using low power irradiation of the water resonance during 2s of relaxation delay. NMR data were processed using VNMRJ (Varian Instrument) software and all the chemical shifts were referenced to the methyl resonance of N-acetyl aspartate (NAA) peak at 2.0 ppm. Total 10 metabolites such as N-acetyl aspartate (NAA), creatine (Cr), choline (Cho), glutamine (Gln), glutamate (Glu), myo-inositol (Ins), lactate (Lac), taurine (Tau), ${\gamma}$-aminobutyricacid (GABA), alanine (Ala) were included for major target metabolites. Symmetrical 2D-COSY spectra were successfully acquired. Total 14 COSY cross peaks were observed even though there were parallel/orthogonal noisy peaks induced by water suppression. Except for Cr, all of human brain metabolites produced COSY cross peaks. The spectra of NAA methyl proton at 2.02 ppm and Glu methylene proton ($CH_2(3)$) at 2.11 ppm and Gln methylene proton ($CH_2(3)$) at 2.14 ppm were overlapped in the similar resonance frequency between 2.00 ppm and 2.15 ppm. The present study demonstrated that in vitro 2D-COSY represented the 3-bond connectivity of human brain metabolites by scalar coupling interaction. This study could aid in better understanding the interactions between human brain metabolites in vivo 2D-COSY study. Also it would be helpful to determine the molecular stereochemistry in vivo by using two-dimensional MR spectroscopy.
This study proposed a rainfall-runoff model for the purpose of real-time flood warning in urban basins. The proposed model was based on the shot noise process, which is expressed as a sum of shot noises determined independently with the peak value, decay parameter and time delay of each sub-basin. The proposed model was different from other rainfall-runoff models from the point that the runoff from each sub-basin reaches the basin outlet independently. The model parameters can be easily determined by the empirical formulas for the concentration time and storage coefficient of a basin and those of the pipe flow. The proposed model was applied to the total of three rainfall events observed at the Jungdong, Guro 1 and Daerim 2 pumping stations to evaluate its applicability. Summarizing the results is as follows. (1) The unit response function of the proposed model, different from other rainfall-runoff models, has the same shape regardless of the rainfall duration. (2) The proposed model shows a convergent shape as the calculation time interval becomes smaller. As the proposed model was proposed to be applied to urban basins, one-minute of calculation time interval would be most appropriate. (3) Application of the one-minute unit response function to the observed rainfall events showed that the simulated runoff hydrographs were very similar to those observed. This result indicates that the proposed model has a good application potential for the rainfall-runoff analysis in urban basins.
Proceedings of the Korean Vacuum Society Conference
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2013.08a
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pp.155.2-155.2
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2013
Strain-relaxed SiGe layer on Si substrate has numerous potential applications for electronic and opto- electronic devices. SiGe layer must have a high degree of strain relaxation and a low dislocation density. Conventionally, strain-relaxed SiGe on Si has been manufactured using compositionally graded buffers, in which very thick SiGe buffers of several micrometers are grown on a Si substrate with Ge composition increasing from the Si substrate to the surface. In this study, a new plasma process, i.e., the combination of PIII&D and HiPIMS, was adopted to implant Ge ions into Si wafer for direct formation of SiGe layer on Si substrate. Due to the high peak power density applied the Ge sputtering target during HiPIMS operation, a large fraction of sputtered Ge atoms is ionized. If the negative high voltage pulse applied to the sample stage in PIII&D system is synchronized with the pulsed Ge plasma, the ion implantation of Ge ions can be successfully accomplished. The PIII&D system for Ge ion implantation on Si (100) substrate was equipped with 3'-magnetron sputtering guns with Ge and Si target, which were operated with a HiPIMS pulsed-DC power supply. The sample stage with Si substrate was pulse-biased using a separate hard-tube pulser. During the implantation operation, HiPIMS pulse and substrate's negative bias pulse were synchronized at the same frequency of 50 Hz. The pulse voltage applied to the Ge sputtering target was -1200 V and the pulse width was 80 usec. While operating the Ge sputtering gun in HiPIMS mode, a pulse bias of -50 kV was applied to the Si substrate. The pulse width was 50 usec with a 30 usec delay time with respect to the HiPIMS pulse. Ge ion implantation process was performed for 30 min. to achieve approximately 20 % of Ge concentration in Si substrate. Right after Ge ion implantation, ~50 nm thick Si capping layer was deposited to prevent oxidation during subsequent RTA process at $1000^{\circ}C$ in N2 environment. The Ge-implanted Si samples were analyzed using Auger electron spectroscopy, High-resolution X-ray diffractometer, Raman spectroscopy, and Transmission electron microscopy to investigate the depth distribution, the degree of strain relaxation, and the crystalline structure, respectively. The analysis results showed that a strain-relaxed SiGe layer of ~100 nm thickness could be effectively formed on Si substrate by direct Ge ion implantation using the newly-developed PIII&D process for non-gaseous elements.
Journal of the Korea Academia-Industrial cooperation Society
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v.22
no.6
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pp.566-572
/
2021
A methodology for the identification and coordinates estimation of air cavities under urban ground or sandy soil using its natural poles and natural resonant frequencies is presented. The potential of this methodology was analyzed. Simulation models of PEC (Perfect Electric Conductor)s with various shapes and dimensions were developed using an EM (Electromagnetic) simulator. The Cauchy method was applied to the obtained EM scattering response of various objects from EM simulation models. The natural poles of objects corresponding to its instinct characterization were then extracted. Thus, a library of poles can be generated using their natural poles. The generated library of poles provided the possibility of identifying a target by comparing them with the computed natural poles from a target. The simulation models were made assuming that there is an air cavity under urban ground or sandy soil. The response of the desired target was extracted from the electromagnetic wave scattering data from its simulation model. The coordinates of the target were estimated using the time delay of the impulse response (peak of the impulse response) in the time domain. The MP (Matrix Pencil) method was applied to extract the natural poles of a target. Finally, a 0.2-m-diameter spherical air cavity underground could be estimated by comparing both the pole library of the objects and the calculated natural poles and the natural resonant frequency of the target. The computed location (depth) of a target showed an accuracy of approximately 84 to 93%.
Park, Sung-ho;Lee, Yoseph;Kang, Sungkwan;Cho, Hyonbae;Yun, Ilsoo
The Journal of The Korea Institute of Intelligent Transport Systems
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v.20
no.3
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pp.1-19
/
2021
The domastic hard shoulder running(HSR) System has been gradually expanding since its initial implementation in September 2007 with the aim of increasing capacity and resolving congestion. Hard Shoulder is used as a space for driver's visual comfort and a place for vehicles to evacuate in case of emergency, but it is replaced by a space for driving when the HSR System is implemented. Therefore, it was intended to determine the improvement effect before and after implementation of the HSR system through safety analysis and mobility analysis. The safety analysis analyzed the impact of traffic accidents by comparing HSR sections and similar sections. The mobility analysis was to determine the improvement effect by quantifying the speed and traffic volume changes before and after HSR System implementation. According to safety yanalysis, there is no effect of reducing traffic accidents when implementing the HSR System. In mobility analysis, the implementation of the HSR System significantly improved the speed of traffic during peak hours and significantly reduces slow and delay hours.
Journal of Korean Society of Disaster and Security
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v.17
no.2
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pp.1-11
/
2024
Most reservoirs in South Korea are earthen dams, mainly because they are cost-effective and easy to construct. However, earthen dams are highly vulnerable to seepage and overtopping, making them prone to sudden failure during excessive flooding. Such sudden failures can lead to a rapid increase in flood discharge, causing significant damage to downstream rivers and inhabited areas. This study investigates the effect of riprap placement on the slopes of earthen dams in delaying dam failure. Delaying the failure time is crucial as it allows more time for evacuation, significantly reducing potential casualties, which is essential from a disaster response perspective. Hydraulic experiments were conducted in a straight channel, using two different sizes of riprap for protection. Unlike previous studies, these experiments were performed under unsteady flow conditions to reflect the impact of rising water levels inside the dam. The target dam for the study was a cofferdam installed in a diversion tunnel. Experimental results indicated that the presence of riprap protection effectively prevented slope failure under the tested conditions. Without riprap protection, increasing the size of the riprap delayed the failure time. This delay can reduce peak discharge, mitigating damage downstream of the dam. Furthermore, these findings can serve as critical reference material for establishing emergency action plans (EAP) for reservoir failure.
Naked barley flour(Baekdong cultivar) was examined with respect to its pasting properties by means of Brabender amylograph after adding barley lipids, fatty acids, vegetable oils and emulsifiers at 1% level. Amylogram of barley flour showed a similar gelatinization temperature but higher paste viscosities at all reference points as compared with wheat flour. Barley flour showed lower amylograph curves by defatting with n-hexane, namely reductions in initial gelatinization point, maximum viscosity and setback value. But re-addition of n-hexane extract to the defatted flour essentially reproduced the curve obtained in the undefatted flour. Addition of polar and nonpolar lipids exhibited different effects on the pasting properties of barley flour. Polar lipids generally increased maximum viscosity a little while non-polar lipids increased the maximum viscosity substantially. Addition of increasing amounts of nonpolar lipids was found to progressively increase the maximum viscosity. Addition of fatty acids increaed th maximum viscosity and delayed the peak time. The maximum viscosity of defatted barley flour impregnated with unsaturated fatty acids was higher than that of defatted barley flour impregnated with saturated fatty acids Increasing amounts of linoleic acid were fount to progressively increase the maximum viscosity and to delay the peak time of defatted barley flour. Addition of six vegetable oils lowered the gelatinization temperature and rasied the maximum viscosity and temperature at maximum viscosity. Addition of increasing amount of peanut oil was found to decrease the maximum viscosity. The effect of emulsifiers was greater in undefatted flour than in defatted flour. The maximum viscosity of defatted flour was slightly affected by Methocel 50, Methocel 1500 and Emulthin, and substantially increased by Methocel 4000, sodium polyacrylate and calcium stearyl lactylate.
Journal of Korean Society of Disaster and Security
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v.12
no.2
/
pp.73-82
/
2019
Recently, as the occurrence frequency of sudden floods due to climate change increased, the flood damage on riverside social infrastructures was extended so that there has been a threat of overflow. Therefore, a rapid prediction of potential flooding in riverside social infrastructure is necessary for administrators. However, most current flood forecasting models including hydraulic model have limitations which are the high accuracy of numerical results but longer simulation time. To alleviate such limitation, data driven models using artificial neural network have been widely used. However, there is a limitation that the existing models can not consider the time-series parameters. In this study the water surface elevation of the Hangang River bridge was predicted using the NARX model considering the time-series parameter. And the results of the ANN and RNN models are compared with the NARX model to determine the suitability of NARX model. Using the 10-year hydrological data from 2009 to 2018, 70% of the hydrological data were used for learning and 15% was used for testing and evaluation respectively. As a result of predicting the water surface elevation after 3 hours from the Hangang River bridge in 2018, the ANN, RNN and NARX models for RMSE were 0.20 m, 0.11 m, and 0.09 m, respectively, and 0.12 m, 0.06 m, and 0.05 m for MAE, and 1.56 m, 0.55 m and 0.10 m for peak errors respectively. By analyzing the error of the prediction results considering the time-series parameters, the NARX model is most suitable for predicting water surface elevation. This is because the NARX model can learn the trend of the time series data and also can derive the accurate prediction value even in the high water surface elevation prediction by using the hyperbolic tangent and Rectified Linear Unit function as an activation function. However, the NARX model has a limit to generate a vanishing gradient as the sequence length becomes longer. In the future, the accuracy of the water surface elevation prediction will be examined by using the LSTM model.
Purpose: Extracellular signal-regulated kinase (ERK), which is part of the mitogen-activated protin kinase cascade, opposes initiation of the apoptotic cell death which is programmed by diverse cytotoxic stimuli. In this regard, the inhibition of ERK may be useful in improving the therapeutic efficacy of established anticancer agents. Materials and Methods: Murine hepatocarcinoma, HCa-I is known to be highly radioresistant with a TCD50 (radiation dose yield in $50\%$ cure) of more than 80 Gy. Various anticancer drugs have been found to enhance the radioresponse of this particular tumor but none were successful. The objective of this study was to explore whether the selective inhibition of MEK could potentiate the antitumor efficacy of radiation in vivo, particularly in the case on radioresistant tumor. C3H/HeJ mice hearing $7.5\~8\;mm$ HCa-I, were treated with PD98059(intratumoral injection of $0.16\;\mug/50\;\mul$). Results: Downregulation on ERK by PD98059 was most prominent 1h after the treatment. In the tumor growth delay assay, the drug was found to Increase the effect of the tumor radioresponse with an enhancement factor (EF) of 1.6 and 1.87. Combined treatment of 25 Gy radiation with PD98059 significantly increased radiation induced apoptosis. The peak apoptotic index (number on apoptotic nuclei in 1000 nuclei X100) was $1.2\%$ in the case of radiation treatment alone, $0.9\%$ in the case of drug treatment alone and $4.9\%,\;5.3\%$ in the combination treatment group. An analysis of apoptosis regulating molecules with Western blotting showed upregulation of p53, p$p21^{WAF1/CIP1}\;and\;Bcl-X_s$ in the combination treatment group as compared to their levels in either the radiation alone or drug alone treatment groups. The level of other molecules such as $Bcl-X_L4, Bax and Bcl-2 were changed to a lesser extent. Conclusion: The selective inhibition of MEK in combination with radiation therapy may have potential benefit in cancer treatment.
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