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Evaluation of the antimalarial activity of SAM13-2HCl with morpholine amide (SKM13 derivative) against antimalarial drug-resistant Plasmodium falciparum and Plasmodium berghei infected ICR mice

  • Hyelee Hong;Kwonmo Moon;Thuy-Tien Thi Trinh;Tae-Hui Eom;Hyun Park;Hak Sung Kim;Seon-Ju Yeo
    • Parasites, Hosts and Diseases
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    • v.62 no.1
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    • pp.42-52
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    • 2024
  • Antimalarial drugs are an urgently need and crucial tool in the campaign against malaria, which can threaten public health. In this study, we examined the cytotoxicity of the 9 antimalarial compounds chemically synthesized using SKM13-2HCl. Except for SKM13-2HCl, the 5 newly synthesized compounds had a 50% cytotoxic concentration (CC50) >100 μM, indicating that they would be less cytotoxic than SKM13-2HCl. Among the 5 compounds, only SAM13-2HCl outperformed SKM13-2HCl for antimalarial activity, showing a 3- and 1.3-fold greater selective index (SI) (CC50/IC50) than SKM13-2HCl in vitro against both chloroquine-sensitive (3D7) and chloroquine -resistant (K1) Plasmodium falciparum strains, respectively. Thus, the presence of morpholine amide may help to effectively suppress human-infectious P. falciparum parasites. However, the antimalarial activity of SAM13-2HCl was inferior to that of the SKM13-2HCl template compound in the P. berghei NK65-infected mouse model, possibly because SAM13-2HCl had a lower polarity and less efficient pharmacokinetics than SKM13-2HCl. SAM13-2HCl was more toxic in the rodent model. Consequently, SAM13-2HCl containing morpholine was selected from screening a combination of pharmacologically significant structures as being the most effective in vitro against human-infectious P. falciparum but was less efficient in vivo in a P. berghei-infected animal model when compared with SKM13-2HCl. Therefore, SAM13-2HCl containing morpholine could be considered a promising compound to treat chloroquine-resistant P. falciparum infections, although further optimization is crucial to maintain antimalarial activity while reducing toxicity in animals.

Defect analysis of calcium fluoride single crystal substrates with (100) and (111) orientation ((100) 및 (111) 배향을 갖는 CaF2 단결정 기판의 결함 분석)

  • Ye-Jin Choi;Min-Gyu Kang;Gi-Uk Lee;Mi-Seon Park;Kwang-Hee Jung;Hea-Kyun Jung;Doo-Gun Kim;Won-Jae Lee
    • Journal of the Korean Crystal Growth and Crystal Technology
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    • v.34 no.1
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    • pp.8-15
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    • 2024
  • The CaF2 single crystal has notable characteristics such as a large band gap (12 eV), excellent transparency over a wide wavelength range, low refractive index and dispersion. Due to these outstanding properties, CaF2 single crystal has considered as a promising material for short-wavelength light sources in recent lithography processes. However, there is an inherent birefringence of the material at 157 nm and the resulting aberration can be compensated for through the combination of the (100) plane and the (111) plane. Therefore, it is necessary to investigate the characteristics according to the plane. In this study, we analyzed crystallinity, optical properties of commercial CaF2 single crystal wafers grown by the Czochralski method. In particular, through chemical etching under various conditions, it was confirmed that the shape of etch pits appears differently depending on the plane and the shape and array of specific etch pits affected by dislocations and defects were examined.

Analyses of Synchronous Fluorescence Spectra of Dissolved Organic Matter for Tracing Upstream Pollution Sources in Rivers (상류 오염원 추적을 위한 용존 유기물질 Synchronous 형광스펙트럼 분석 연구)

  • Hur, Jin;Kim, Mi-Kyoung;Park, Sung-Won
    • Journal of Korean Society of Environmental Engineers
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    • v.29 no.3
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    • pp.317-324
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    • 2007
  • Fluorescence measurements of dissolved organic matter(DOM) have the superior advantages over other analysis tools for applying to water quality management. A preliminary study was conducted to test the feasibility of applying synchronous fluorescence measurements for tracing and monitoring pollution sources in a small stream located in an upstream area of the Sooyoung watershed in Busan. The water quality of the small stream is affected by leachate from sawdust pile and discharge of untreated sewage. The sampling sites included an upstream site, two pipes discharging untreated sewage, leachate from sawdust, and a downstream site. Of the five field samples, the leachate was distinguished from the other samples by a high peak at a lower wavelength range and a blunt peak at 350nm, suggesting that synchronous fluorescence can be used as a discrimination tool for monitoring the pollution. The efficacy of various indices derived from the spectral features to discriminate the pollution source was tested for well-defined mixture of the sawdust leachate and the upstream stream by comparing (1)the difference between measured values and those predicted based on mass balance and the characteristics of the two samples and (2)the linear correlations between index values and mass ratios of the sample mixtures. Of various discrimination indices selected, fluorescence intensities at 276 nm$({\Delta}\lambda=30nm)$and 347 nm$({\Delta}\lambda=60nm)$ were suggested as promising potential discrimination indices for the sawdust pollution source. Despite the limited number of samples and the study area, this study illustrates the evaluation process that should be followed to develop rapid, low-cost discrimination indices to monitor pollution sources based on end member mixing analyses.

Comparative Assessment of Linear Regression and Machine Learning for Analyzing the Spatial Distribution of Ground-level NO2 Concentrations: A Case Study for Seoul, Korea (서울 지역 지상 NO2 농도 공간 분포 분석을 위한 회귀 모델 및 기계학습 기법 비교)

  • Kang, Eunjin;Yoo, Cheolhee;Shin, Yeji;Cho, Dongjin;Im, Jungho
    • Korean Journal of Remote Sensing
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    • v.37 no.6_1
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    • pp.1739-1756
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    • 2021
  • Atmospheric nitrogen dioxide (NO2) is mainly caused by anthropogenic emissions. It contributes to the formation of secondary pollutants and ozone through chemical reactions, and adversely affects human health. Although ground stations to monitor NO2 concentrations in real time are operated in Korea, they have a limitation that it is difficult to analyze the spatial distribution of NO2 concentrations, especially over the areas with no stations. Therefore, this study conducted a comparative experiment of spatial interpolation of NO2 concentrations based on two linear-regression methods(i.e., multi linear regression (MLR), and regression kriging (RK)), and two machine learning approaches (i.e., random forest (RF), and support vector regression (SVR)) for the year of 2020. Four approaches were compared using leave-one-out-cross validation (LOOCV). The daily LOOCV results showed that MLR, RK, and SVR produced the average daily index of agreement (IOA) of 0.57, which was higher than that of RF (0.50). The average daily normalized root mean square error of RK was 0.9483%, which was slightly lower than those of the other models. MLR, RK and SVR showed similar seasonal distribution patterns, and the dynamic range of the resultant NO2 concentrations from these three models was similar while that from RF was relatively small. The multivariate linear regression approaches are expected to be a promising method for spatial interpolation of ground-level NO2 concentrations and other parameters in urban areas.

On Using Near-surface Remote Sensing Observation for Evaluation Gross Primary Productivity and Net Ecosystem CO2 Partitioning (근거리 원격탐사 기법을 이용한 총일차생산량 추정 및 순생태계 CO2 교환량 배분의 정확도 평가에 관하여)

  • Park, Juhan;Kang, Minseok;Cho, Sungsik;Sohn, Seungwon;Kim, Jongho;Kim, Su-Jin;Lim, Jong-Hwan;Kang, Mingu;Shim, Kyo-Moon
    • Korean Journal of Agricultural and Forest Meteorology
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    • v.23 no.4
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    • pp.251-267
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    • 2021
  • Remotely sensed vegetation indices (VIs) are empirically related with gross primary productivity (GPP) in various spatio-temporal scales. The uncertainties in GPP-VI relationship increase with temporal resolution. Uncertainty also exists in the eddy covariance (EC)-based estimation of GPP, arising from the partitioning of the measured net ecosystem CO2 exchange (NEE) into GPP and ecosystem respiration (RE). For two forests and two agricultural sites, we correlated the EC-derived GPP in various time scales with three different near-surface remotely sensed VIs: (1) normalized difference vegetation index (NDVI), (2) enhanced vegetation index (EVI), and (3) near infrared reflectance from vegetation (NIRv) along with NIRvP (i.e., NIRv multiplied by photosynthetically active radiation, PAR). Among the compared VIs, NIRvP showed highest correlation with half-hourly and monthly GPP at all sites. The NIRvP was used to test the reliability of GPP derived by two different NEE partitioning methods: (1) original KoFlux methods (GPPOri) and (2) machine-learning based method (GPPANN). GPPANN showed higher correlation with NIRvP at half-hourly time scale, but there was no difference at daily time scale. The NIRvP-GPP correlation was lower under clear sky conditions due to co-limitation of GPP by other environmental conditions such as air temperature, vapor pressure deficit and soil moisture. However, under cloudy conditions when photosynthesis is mainly limited by radiation, the use of NIRvP was more promising to test the credibility of NEE partitioning methods. Despite the necessity of further analyses, the results suggest that NIRvP can be used as the proxy of GPP at high temporal-scale. However, for the VIs-based GPP estimation with high temporal resolution to be meaningful, complex systems-based analysis methods (related to systems thinking and self-organization that goes beyond the empirical VIs-GPP relationship) should be developed.

Rough Set Analysis for Stock Market Timing (러프집합분석을 이용한 매매시점 결정)

  • Huh, Jin-Nyung;Kim, Kyoung-Jae;Han, In-Goo
    • Journal of Intelligence and Information Systems
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    • v.16 no.3
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    • pp.77-97
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    • 2010
  • Market timing is an investment strategy which is used for obtaining excessive return from financial market. In general, detection of market timing means determining when to buy and sell to get excess return from trading. In many market timing systems, trading rules have been used as an engine to generate signals for trade. On the other hand, some researchers proposed the rough set analysis as a proper tool for market timing because it does not generate a signal for trade when the pattern of the market is uncertain by using the control function. The data for the rough set analysis should be discretized of numeric value because the rough set only accepts categorical data for analysis. Discretization searches for proper "cuts" for numeric data that determine intervals. All values that lie within each interval are transformed into same value. In general, there are four methods for data discretization in rough set analysis including equal frequency scaling, expert's knowledge-based discretization, minimum entropy scaling, and na$\ddot{i}$ve and Boolean reasoning-based discretization. Equal frequency scaling fixes a number of intervals and examines the histogram of each variable, then determines cuts so that approximately the same number of samples fall into each of the intervals. Expert's knowledge-based discretization determines cuts according to knowledge of domain experts through literature review or interview with experts. Minimum entropy scaling implements the algorithm based on recursively partitioning the value set of each variable so that a local measure of entropy is optimized. Na$\ddot{i}$ve and Booleanreasoning-based discretization searches categorical values by using Na$\ddot{i}$ve scaling the data, then finds the optimized dicretization thresholds through Boolean reasoning. Although the rough set analysis is promising for market timing, there is little research on the impact of the various data discretization methods on performance from trading using the rough set analysis. In this study, we compare stock market timing models using rough set analysis with various data discretization methods. The research data used in this study are the KOSPI 200 from May 1996 to October 1998. KOSPI 200 is the underlying index of the KOSPI 200 futures which is the first derivative instrument in the Korean stock market. The KOSPI 200 is a market value weighted index which consists of 200 stocks selected by criteria on liquidity and their status in corresponding industry including manufacturing, construction, communication, electricity and gas, distribution and services, and financing. The total number of samples is 660 trading days. In addition, this study uses popular technical indicators as independent variables. The experimental results show that the most profitable method for the training sample is the na$\ddot{i}$ve and Boolean reasoning but the expert's knowledge-based discretization is the most profitable method for the validation sample. In addition, the expert's knowledge-based discretization produced robust performance for both of training and validation sample. We also compared rough set analysis and decision tree. This study experimented C4.5 for the comparison purpose. The results show that rough set analysis with expert's knowledge-based discretization produced more profitable rules than C4.5.

Comparison of Natural Flow Estimates for the Han River Basin Using TANK and SWAT Models (TANK 모형과 SWAT 모형을 이용한 한강유역의 자연유출량 산정 비교)

  • Kim, Chul-Gyum;Kim, Nam-Won
    • Journal of Korea Water Resources Association
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    • v.45 no.3
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    • pp.301-316
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    • 2012
  • Two models, TANK and SWAT (Soil and Water Assessment Tool) were compared for simulating natural flows in the Paldang Dam upstream areas of the Han River basin in order to understand the limitations of TANK and to review the applicability and capability of SWAT. For comparison, simulation results from the previous research work were used. In the results for the calibrated watersheds (Chungju Dam and Soyanggang Dam), two models provided promising results for forecasting of daily flows with the Nash-Sutcliffe model efficiency of around 0.8. TANK simulated observations during some peak flood seasons better than SWAT, while it showed poor results during dry seasons, especially its simulations did not fall down under a certain value. It can be explained that TANK was calibrated for relatively larger flows than smaller ones. SWAT results showed a relatively good agreement with observed flows except some flood flows, and simulated inflows at the Paldang Dam considering discharges from upper dams coincided with observations with the model efficiency of around 0.9. This accounts for SWAT applicability with higher accuracy in predicting natural flows without dam operation or artificial water uses, and in assessing flow variations before and after dam development. Also, two model results were compared for other watersheds such as Pyeongchang-A, Dalcheon-B, Seomgang-B, Inbuk-A, Hangang-D, and Hongcheon-A to which calibrated TANK parameters were applied. The results were similar to the case of calibrated watersheds, that TANK simulated poor smaller flows except some flood flows and had same problem of keeping on over a certain value in dry seasons. This indicates that TANK application may have fatal uncertainties in estimating low flows used as an important index in water resources planning and management. Therefore, in order to reflect actually complex and complicated physical characteristics of Korean watersheds, and to manage efficiently water resources according to the land use and water use changes with urbanization or climate change in the future, it is necessary to utilize a physically based watershed model like SWAT rather than an existing conceptual lumped model like TANK.

Effect of ω3-Fatty Acid Desaturase Gene Expression on Invasion and Tumorigenicity in Human Tongue Squamous Cell Carcinoma Cells (인체 혀의 편평세포암 세포에서 ω3-fatty acid desaturase 유전자 발현이 침윤 및 종양형성에 미치는 영향)

  • Hong, Tae-Hwa;Shin, Soyeon;Han, Seung-Hyeon;Hwang, Byung-Doo;Lim, Kyu
    • Journal of Life Science
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    • v.28 no.8
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    • pp.945-954
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    • 2018
  • Omega-3 polyunsaturated fatty acids (${\omega}3$-fatty acid) have been found to possess anticancer properties in a variety of cancer cell lines and animal models, but their effects in human tongue squamous cell carcinomas (SCCs) remain unclear. This study was designed to examine the effect of ${\omega}3$-fatty acid desaturase (fat-1) gene expression on invasion and tumorigenicity in human tongue SCC cells and the molecular mechanism of its action. Docosahexaenoic acid (DHA) treatment inhibited in vitro invasion in a dose-dependent manner. In zymography, matrix metalloproteinase-9 (MMP-9) and Matrix metallopeptidase-2 (MMP-2) activities were reduced, and MMP-9 and MMP-2 promoter activities were inhibited by the DHA treatment. In addition, cyclooxygenase-2 (COX-2) and vascular endothelial growth factor (VEGF) promoter reporter activities were inhibited in SCC-4 and SCC-9 cells after the DHA treatment. To investigate the effect of a high level of endogenous ${\omega}3$ fatty acids, a stable SCC-9 cell line expressing the ${\omega}3$-desaturase gene (fSCC-9sc) was generated. The growth rate and colony-forming capacity of fSCC-9sc were remarkably decreased as compared with those of fSCC-9cc. Likewise, the tumor size and volume of fSCC-9sc implanted into nude mice were significantly inhibited, with increases in the cell death index. Furthermore, a transwell chamber invasion assay showed a reduction in cell invasion of the fSCC-9sc lines when compared with that of the fSCC-9cc line. These findings suggested that fat-1 gene expression inhibited tumorigenicity, as well as invasion in human tongue SCC cells. Thus, utilization of ${\omega}3$ fatty acids may represent a promising therapeutic approach for chemoprevention and the treatment of human tongue SCCs.

Characterization and annealing effect of tantalum oxide thin film by thermal chemical (열CVD방법으로 증착시킨 탄탈륨 산화박막의 특성평가와 열처리 효과)

  • Nam, Gap-Jin;Park, Sang-Gyu;Lee, Yeong-Baek;Hong, Jae-Hwa
    • Korean Journal of Materials Research
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    • v.5 no.1
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    • pp.42-54
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    • 1995
  • $Ta_2O_5$ thin film IS a promising material for the high dielectrics of ULSI DRAM. In this study, $Ta_2O_5$ thin film was grown on p-type( 100) Si wafer by thermal metal organic chemical vapo deposition ( MCCVD) method and the effect of operating varialbles including substrate temperature( $T_s$), bubbler temperature( $T_ \sigma$), reactor pressure( P ) was investigated in detail. $Ta_2O_5$ thin film were analyzed by SEM, XRD, XPS, FT-IR, AES, TEM and AFM. In addition, the effect of various anneal methods was examined and compared. Anneal methods were furnace annealing( FA) and rapid thermal annealing( RTA) in $N_{2}$ or $O_{2}$ ambients. Growth rate was evidently classified into two different regimes. : (1) surface reaction rate-limited reglme in the range of $T_s$=300 ~ $400 ^{\circ}C$ and (2: mass transport-limited regime in the range of $T_s$=400 ~ $450^{\circ}C$.It was found that the effective activation energies were 18.46kcal/mol and 1.9kcal/mol, respectively. As the bubbler temperature increases, the growth rate became maximum at $T_ \sigma$=$140^{\circ}C$. With increasing pressure, the growth rate became maximum at P=3torr but the refractive index which is close to the bulk value of 2.1 was obtained in the range of 0.1 ~ 1 torr. Good step coverage of 85. 71% was obtained at $T_s$=$400 ^{\circ}C$ and sticking coefficient was 0.06 by comparison with Monte Carlo simulation result. From the results of AES, FT-IR and E M , the degree of SiO, formation at the interface between Si and TazO, was larger in the order of FA-$O_{2}$ > RTA-$O_{2}$, FA-$N_{2}$ > RTA-$N_{2}$. However, the $N_{2}$ ambient annealing resulted in more severe Weficiency in the $Ta_2O_5$ thin film than the TEX>$O_{2}$ ambient.

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Evaluation of the Accuracy for Respiratory-gated RapidArc (RapidArc를 이용한 호흡연동 회전세기조절방사선치료 할 때 전달선량의 정확성 평가)

  • Sung, Jiwon;Yoon, Myonggeun;Chung, Weon Kuu;Bae, Sun Hyun;Shin, Dong Oh;Kim, Dong Wook
    • Progress in Medical Physics
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    • v.24 no.2
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    • pp.127-132
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    • 2013
  • The position of the internal organs can change continually and periodically inside the body due to the respiration. To reduce the respiration induced uncertainty of dose localization, one can use a respiratory gated radiotherapy where a radiation beam is exposed during the specific time of period. The main disadvantage of this method is that it usually requests a long treatment time, the massive effort during the treatment and the limitation of the patient selection. In this sense, the combination of the real-time position management (RPM) system and the volumetric intensity modulated radiotherapy (RapidArc) is promising since it provides a short treatment time compared with the conventional respiratory gated treatments. In this study, we evaluated the accuracy of the respiratory gated RapidArc treatment. Total sic patient cases were used for this study and each case was planned by RapidArc technique using varian ECLIPSE v8.6 planning machine. For the Quality Assurance (QA), a MatriXX detector and I'mRT software were used. The results show that more than 97% of area gives the gamma value less than one with 3% dose and 3 mm distance to agreement condition, which indicates the measured dose is well matched with the treatment plan's dose distribution for the gated RapidArc treatment cases.