• Title/Summary/Keyword: surrogate

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Bioactivity-guided isolation of ginsenosides from Korean Red Ginseng with cytotoxic activity against human lung adenocarcinoma cells

  • Yu, Jae Sik;Roh, Hyun-Soo;Baek, Kwan-Hyuck;Lee, Seul;Kim, Sil;So, Hae Min;Moon, Eunjung;Pang, Changhyun;Jang, Tae Su;Kim, Ki Hyun
    • Journal of Ginseng Research
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    • v.42 no.4
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    • pp.562-570
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    • 2018
  • Background: Lung cancer is the leading cause of cancer-related death worldwide. In this study, we used a bioactivity-guided isolation technique to identify constituents of Korean Red Ginseng (KRG) with antiproliferative activity against human lung adenocarcinoma cells. Methods: Bioactivity-guided fractionation and preparative/semipreparative HPLC purification were used with LC/MS analysis to separate the bioactive constituents. Cell viability and apoptosis in human lung cancer cell lines (A549, H1264, H1299, and Calu-6) after treatment with KRG extract fractions and constituents thereof were assessed using the water-soluble tetrazolium salt (WST-1) assay and terminal deoxyribonucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining, respectively. Caspase activation was assessed by detecting its surrogate marker, cleaved poly adenosine diphosphate (ADP-ribose) polymerase, using an immunoblot assay. The expression and subcellular localization of apoptosis-inducing factor were assessed using immunoblotting and immunofluorescence, respectively. Results and conclusion: Bioactivity-guided fractionation of the KRG extract revealed that its ethyl acetate-soluble fraction exerts significant cytotoxic activity against all human lung cancer cell lines tested by inducing apoptosis. Chemical investigation of the ethyl acetatesoluble fraction led to the isolation of six ginsenosides, including ginsenoside Rb1 (1), ginsenoside Rb2 (2), ginsenoside Rc (3), ginsenoside Rd (4), ginsenoside Rg1 (5), and ginsenoside Rg3 (6). Among the isolated ginsenosides, ginsenoside Rg3 exhibited the most cytotoxic activity against all human lung cancer cell lines examined, with $IC_{50}$ values ranging from $161.1{\mu}M$ to $264.6{\mu}M$. The cytotoxicity of ginsenoside Rg3 was found to be mediated by induction of apoptosis in a caspase-independent manner. These findings provide experimental evidence for a novel biological activity of ginsenoside Rg3 against human lung cancer cells.

A Preliminary Survey of Attitude Towards IVF Surrogacy (체외수정을 통한 대리모 출산에 대한 인식 조사)

  • Park, Joon-Cheol;Kim, Jong-In;Rhee, Jeong-Ho
    • Clinical and Experimental Reproductive Medicine
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    • v.34 no.2
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    • pp.75-85
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    • 2007
  • Objectives: The aim of this study was to find out the attitude of Korean women towards IVF surrogacy which is not yet regulated by the law. Methods: We evaluated with a questionnaire, in how far IVF surrogacy was accepted in different groups of Korean women. Total 300 questionnaires were sent out to women who visited our infertility clinic, and to the nurses and office workers of our hospital. Among them, 246 questionnaires were returned, and 211 of them (85.7%) were complete and analyzed. The responders were 58 unmarried women and 153 married women including 60 infertile patients. Results: Only 17 (8.1%) women believed that IVF surrogacy was an acceptable treatment for infertile women without uterus (eg. MRKH or hysterectomized patients), and 125 (59.2%) women chose the adoption. There were no significant differences in response amongst different age group, marital status, or in relation to income level or educational level, or infertility status. A significantly higher level of acceptance was noted only in religious groups, especially in Christians. Most of responders (66.5%) chose unrelated and unknown women as a desirable host, and 28.4% of responders chose the sister or sister-in-law. Conclusions: Overall the different groups were critical towards IVF Surrogacy in Korea, irrespective of the infertile patient group. Despite the established clinical ability to have her own genetic child in women without uterus, this survey reveals that only minority supports the IVF surrogacy. So we need the survey with large, randomized population and then make a regulation about the IVF surrogacy in law.

Structural Characteristics of Expression Module of Unidentified Genes from Metagenome (메타게놈 유래 미규명 유전자의 발현에 관련된 특성분석)

  • Park, Seung-Hye;Jeong, Young-Su;Kim, Won-Ho;Kim, Geun-Joong;Hur, Byung-Ki
    • KSBB Journal
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    • v.21 no.2
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    • pp.144-150
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    • 2006
  • The exploitation of metagenome, the access to the natural extant of enormous potential resources, is the way for elucidating the functions of organism in environmental communities, for genomic analyses of uncultured microorganism, and also for the recovery of entirely novel natural products from microbial communities. The major breakthrough in metagenomics is opened by the construction of libraries with total DNAs directly isolated from environmental samples and screening of these libraries by activity and sequence-based approaches. Screening with activity-based approach is presumed as a plausible route for finding new catabolic genes under designed conditions without any prior sequence information. The main limitation of these approaches, however, is the very low positive hits in a single round of screening because transcription, translation and appropriate folding are not always possible in E. coli, a typical surrogate host. Thus, to obtain information about these obstacles, we studied the genetic organization of individual URF's(unidentified open reading frame from metagenome sequenced and deposited in GenBank), especially on the expression factors such as codon usage, promoter region and ribosome binding site(rbs), based on DNA sequence analyses using bioinformatics tools. And then we also investigated the above-mentioned properties for 4100 ORFs(Open Reading Frames) of E. coli K-12 generally used as a host cell for the screening of noble genes from metagenome. Finally, we analyzed the differences between the properties of URFs of metagenome and ORFs of E. coli. Information derived from these comparative metagenomic analyses can provide some specific features or environmental blueprint available to screen a novel biocatalyst efficiently.

Precipitation behaviors of Cs and Re(/Tc) by NaTPB and TPPCl from a simulated fission products-$(Na_2CO_3-NaHCO_3)-H_2O_2$ solution (모의 FP-$(Na_2CO_3-NaHCO_3)-H_2O_2$ 용액으로부터 NaTPB 및 TPPCl에 의한 Cs 및 Re(/Tc)의 침전 거동)

  • Lee, Eil-Hee;Lim, Jae-Gwan;Chung, Dong-Yong;Yang, Han-Beum;Kim, Kwang-Wook
    • Journal of Nuclear Fuel Cycle and Waste Technology(JNFCWT)
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    • v.8 no.2
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    • pp.115-122
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    • 2010
  • In this study, the removal of Cs and Tc from a simulated fission products (FP) solution which were co-dissolved with U during the oxidative-dissolution of spent fuel in a mixed carbonate solution of $(Na_2CO_3-NaHCO_3)-H_2O_2$ was investigated by using a selective precipitation method. As Cs and Tc might cause an unstable behavior due to the high decay heat emission of Cs as well as the fast migration of Tc when disposed of underground, it is one of the important issues to removal them in views of the increase of disposal safety. The precipitation of Cs and Re (as a surrogate for Tc) was examined by introducing sodium tetraphenylborate (NaTPB) and tetraphenylphosponium chloride (TPPCl), respectively. Precipitation of Cs by NaTPB and that of Re by TPPCl were completed within 5 minutes. Their precipitation rates were not influenced so much by the temperature and stirring speed even if they were increased by up to $50^{\circ}C$ and 1,000 rpm. However, the pH of the solution was found to have a great influence on the precipitation with NaTPB and TPPCl. Since Mo tends to co-precipitate with Re at a lower pH, especially, it was effective that a selective precipitation of Re by TPPCl was carried out at pH of above 9 without co-precipitation of Mo and Re. Over 99% of Cs was precipitated when the ratio of [NaTPB]/[Cs]>1 and more than 99% of Re, likewise, was precipitated when the ratio of [TPPCl]/[Re]>1.

Quantitative Analysis of Feline Calicivirus Inactivation using Real-time RT-PCR (Real-time RT-PCR을 이용한 Feline Calicivirus 불활성화의 정량적 분석)

  • Jeong, Hye Mi;Kim, Kwang Yup
    • Journal of Food Hygiene and Safety
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    • v.29 no.1
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    • pp.31-39
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    • 2014
  • Norovirus causes acute gastroenteritis in all age groups and its food poisoning outbreaks are rapidly increasing in Korea. Reverse transcription-polymerase chain reaction (RT-PCR) is most widely used for the rapid detection of foodborne viruses due to high sensitivity. However, the false positive results of RT-PCR obtained against already inactivated viruses could be a serious drawbacks in food safety area. In this study, we investigated a method to yield true positive RT-PCR results only with alive viruses. To decompose the RNA genes from dead viruses, the enzymatic treatments composed of proteinse K and Ribonuclease A were applied to the sanitized and inactivated virus particles. Another aim of this study was to quantify the efficiencies of several major sanitizing treatments using real-time RT-PCR. Feline calicivirus (FCV) that belongs to the same Caliciviridae family with norovirus was used as a surrogate model for norovirus. The initial level of virus in control suspension was approximately $10^4$ PFU/mL. Most of inactivated viruses treated with the enzymatic treatment for 30 min at $37^{\circ}C$ were not detected in RT-PCR, Quantification results to verify the inactivation efficiencies of sanitizing treatments using real-time RT-PCR showed no false positive in most cases. We could successfully develope a numerical quantification process for the inactivated viruses after major sanitizing treatments using real-time RT-PCR. The results obtained in this study could provide a novel basis of rapid virus quantification in food safety area.

A Numerical Study on the Extinguishing Effects of CO2 in Counterflow Diffusion Flames with the Concept of Local Application System (국소방출방식 개념의 대향류 확산화염에서 CO2 소화효과에 관한 수치해석 연구)

  • Mun, Sun-Yeo;Park, Chung-Hwa;Hwang, Cheol-Hong;Oh, Chang-Bo
    • Fire Science and Engineering
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    • v.26 no.4
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    • pp.55-62
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    • 2012
  • The suppression mechanisms of carbon dioxide ($CO_2$) as a representative fire suppression agent were revisited using a counterflow diffusion flame which could be applied the concept of a local application system. To end this, the low strain rate $CH_4$/air counterflow diffusions with $CO_2$ addition in either fuel or oxidizer stream were examined numerically using detailed-kinetic chemistry. Radiative heat loss due to radiating gas species including $CO_2$ added was considered by the optically thin model (OTM). As a result, the critical $CO_2$ volume fractions in the oxidizer stream required to extinguish the flame were in good agreement with the experimental data reported in the literature, while somewhat under-prediction was observed with $CO_2$ added in the fuel stream. The surrogate agents were adopted to estimate the quantitative contribution with changing in global strain rate ($a_g$) on the flame extinguishment among pure dilution effect, thermal effects including radiation heat loss and chemical effect due to the $CO_2$ fire suppression agent.

Health and Economic Burden Attributable to Particulate Matter in South Korea: Considering Spatial Variation in Relative Risk (지역간 상대위험도 변동을 고려한 미세먼지 기인 질병부담 및 사회경제적 비용 추정 연구)

  • Byun, Garam;Choi, Yongsoo;Gil, Junsu;Cha, Junil;Lee, Meehye;Lee, Jong-Tae
    • Journal of Environmental Health Sciences
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    • v.47 no.5
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    • pp.486-495
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    • 2021
  • Background: Particulate matter (PM) is one of the leading causes of premature death worldwide. Previous studies in South Korea have applied a relative risk calculated from Western populations when estimating the disease burden attributable to PM. However, the relative risk of PM on health outcomes may not be the same across different countries or regions. Objectives: This study aimed to estimate the premature deaths and socioeconomic costs attributable to long-term exposure to PM in South Korea. We considered not only the difference in PM concentration between regions, but also the difference in relative risk. Methods: National monitoring data of PM concentrations was obtained, and missing values were imputed using the AERMOD model and linear regression model. As a surrogate for relative risk, hazard ratios (HRs) of PM for cardiovascular and respiratory mortality were estimated using the National Health Insurance Service-National Sample Cohort. The nation was divided into five areas (metropolitan, central, southern, south-eastern, and Gangwon-do Province regions). The number of PM attributable deaths in 2018 was calculated at the district level. The socioeconomic cost was derived by multiplying the number of deaths and the statistical value of life. Results: The average PM10 concentration for 2014~2018 was 45.2 ㎍/m3. The association between long-term exposure to PM10 and mortality was heterogeneous between areas. When applying area-specific HRs, 23,811 premature deaths from cardiovascular and respiratory disease in 2018 were attributable to PM10 (reference level 20 ㎍/m3). The corresponding socioeconomic cost was about 31 trillion won. These estimated values were higher than that when applying nationwide HRs. Conclusions: This study is the first research to estimate the premature mortality caused by long-term exposure to PM using relative risks derived from the national population. This study will help precisely identify the national and regional health burden attributed to PM and establish the priorities of air quality policy.

Effect of input variable characteristics on the performance of an ensemble machine learning model for algal bloom prediction (앙상블 머신러닝 모형을 이용한 하천 녹조발생 예측모형의 입력변수 특성에 따른 성능 영향)

  • Kang, Byeong-Koo;Park, Jungsu
    • Journal of Korean Society of Water and Wastewater
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    • v.35 no.6
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    • pp.417-424
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    • 2021
  • Algal bloom is an ongoing issue in the management of freshwater systems for drinking water supply, and the chlorophyll-a concentration is commonly used to represent the status of algal bloom. Thus, the prediction of chlorophyll-a concentration is essential for the proper management of water quality. However, the chlorophyll-a concentration is affected by various water quality and environmental factors, so the prediction of its concentration is not an easy task. In recent years, many advanced machine learning algorithms have increasingly been used for the development of surrogate models to prediction the chlorophyll-a concentration in freshwater systems such as rivers or reservoirs. This study used a light gradient boosting machine(LightGBM), a gradient boosting decision tree algorithm, to develop an ensemble machine learning model to predict chlorophyll-a concentration. The field water quality data observed at Daecheong Lake, obtained from the real-time water information system in Korea, were used for the development of the model. The data include temperature, pH, electric conductivity, dissolved oxygen, total organic carbon, total nitrogen, total phosphorus, and chlorophyll-a. First, a LightGBM model was developed to predict the chlorophyll-a concentration by using the other seven items as independent input variables. Second, the time-lagged values of all the input variables were added as input variables to understand the effect of time lag of input variables on model performance. The time lag (i) ranges from 1 to 50 days. The model performance was evaluated using three indices, root mean squared error-observation standard deviation ration (RSR), Nash-Sutcliffe coefficient of efficiency (NSE) and mean absolute error (MAE). The model showed the best performance by adding a dataset with a one-day time lag (i=1) where RSR, NSE, and MAE were 0.359, 0.871 and 1.510, respectively. The improvement of model performance was observed when a dataset with a time lag up of about 15 days (i=15) was added.

Factors Affecting Basilar Artery Pulsatility Index on Transcranial Doppler (뇌혈류 초음파 검사에서 기저동맥 박동지수에 영향을 미치는 인자)

  • Jeong, Ho Tae;Kim, Dae Sik;Kang, Kun Woo;Nam, Yun Teak;Oh, Ji Eun;Cho, Eun Kyung
    • Korean Journal of Clinical Laboratory Science
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    • v.50 no.4
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    • pp.477-483
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    • 2018
  • Transcranial doppler is a non-invasive method that measures the blood flow velocity and the direction of cerebral blood vessels through the doppler principle. The pulsatility index is an index for measuring the transcranial doppler that reflects the distal vascular resistance and is used as an index for the presence and diffusion of cerebral small vessel diseases. The purpose of this study was to evaluate the risk factors affecting the basilar artery pulsatility index in ischemic stroke patients. From January 2014 to May 2015, 422 patients were selected by measuring the transcranial doppler pulsatility index, considering their basilar artery pulsatility index. Univariate analysis was performed using the basilar artery pulsatility index as a dependent variable. Multiple regression analysis was performed considering the factors affecting the pulsatility index as variables. Univariate analysis revealed age, presence of hypertension, presence of diabetes mellitus, presence of hyperlipidemia, and hematocrit (P<0.1) as factors. Multiple regression analysis showed statistically significant results with age (P<0.001), presence of diabetes (P=0.004), and presence of hyperlipidemia (P=0.041). The risk factors affecting the basilar artery pulsatility index of transcranial doppler were age, diabetes, and hyperlipidemia. Further research will be needed to increase the cerebral pulsatility index as a surrogate marker of the elderly, diabetes, and hyperlipidemia.

Extra-phase Image Generation for Its Potential Use in Dose Evaluation for a Broad Range of Respiratory Motion

  • Lee, Hyun Su;Choi, Chansoo;Kim, Chan Hyeong;Han, Min Cheol;Yeom, Yeon Soo;Nguyen, Thang Tat;Kim, Seonghoon;Choi, Sang Hyoun;Lee, Soon Sung;Kim, Jina;Hwang, JinHo;Kang, Youngnam
    • Journal of Radiation Protection and Research
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    • v.44 no.3
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    • pp.103-109
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    • 2019
  • Background: Four-dimensional computed tomographic (4DCT) images are increasingly used in clinic with the growing need to account for the respiratory motion of the patient during radiation treatment. One of the reason s that makes the dose evaluation using 4DCT inaccurate is a change of the patient respiration during the treatment session, i.e., intrafractional uncertainty. Especially, when the amplitude of the patient respiration is greater than the respiration range during the 4DCT acquisition, such an organ motion from the larger respiration is difficult to be represented with the 4DCT. In this paper, the method to generate images expecting the organ motion from a respiration with extended amplitude was proposed and examined. Materials and Methods: We propose a method to generate extra-phase images from a given set of the 4DCT images using deformable image registration (DIR) and linear extrapolation. Deformation vector fields (DVF) are calculated from the given set of images, then extrapolated according to respiratory surrogate. The extra-phase images are generated by applying the extrapolated DVFs to the existing 4DCT images. The proposed method was tested with the 4DCT of a physical 4D phantom. Results and Discussion: The tumor position in the generated extra-phase image was in a good agreement with that in the gold-standard image which is separately acquired, using the same 4DCT machine, with a larger range of respiration. It was also found that we can generate the best quality extra-phase image by using the maximum inhalation phase (T0) and maximum exhalation phase (T50) images for extrapolation. Conclusion: In the present study, a method to construct extra-phase images that represent expanded respiratory motion of the patient has been proposed and tested. The movement of organs from a larger respiration amplitude can be predicted by the proposed method. We believe the method may be utilized for realistic simulation of radiation therapy.