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Development and Validation of the Determination of Sorafenib in Human Plasma using Tandem Mass Spectrometry Coupled with Liquid Chromatography (고속액체크로마토그래피 텐덤질량분석기법을 이용한 사람 혈장 내 소라페닙 농도분석법의 개발 및 검정)

  • Park, Daejin;Lee, Sunggon;Kim, Woomi
    • Journal of Life Science
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    • v.22 no.11
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    • pp.1456-1462
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    • 2012
  • Sorafenib is a multikinase inhibitor and an oral anticancer drug approved for the treatment of patients with advanced renal cell carcinoma and those with unresectable hepatocellular carcinoma. The purpose of this study was to develop an efficient method of the determination of sorafenib in human plasma using tandem mass spectrometry coupled with liquid chromatography (LC/MS/MS) and validate the method by the guidelines of the Korean Food and Drug Administration (KFDA). Plasma samples ($100{\mu}l$) were added with chlorantraniliprole as an internal standard and then mixed with the 0.1% formic acid-containing extraction solution composed of isopropyl alcohol and ethyl acetate (1:4, v/v). After centrifugation, the supernatant was concentrated at $45^{\circ}C$ under negative pressure and centrifugal force. The residue was reconstituted with a mobile phase and injected into the HPLC instrument using a reverse phase Waters XTerra$^{TM}$ C18 column (particle size $3.5{\mu}m$). Liquid chromatography was carried out within the run time of 5 min using a mobile phase composed of buffer (0.1% formic acid and 10 mM ammonium formate), methanol, and acetonitrile (1:6:3, v/v/v). The analytes were monitored by tandem mass spectrometry in the multiple reaction monitoring method programmed to detect sorafenib at 'm/z 465.2 ${\rightarrow}$ 252.5' and chlorantraniliprole at 'm/z 484.4 ${\rightarrow}$ 286.2' with positive electrospray ionization mode ($ES^+$). The result showed the proper linearity ($r^2$ > 0.99) over the range of 2,000-5,000 ng/ml with good accuracy (90.7-103.9%) and precision (less than 10%). The newly developed method using LC/MS/MS was validated by the guideline of KFDA and identified as more sensitive compared to the previous methods.

Case Study on Economical Fabrication and Erection of Steel Structure and Reduction in Field Erection Time (경제적 철골제작$\cdot$설치 및 공기단축 사례분석연구)

  • Ahn Jae-Bong;Choi Yoon ki
    • Korean Journal of Construction Engineering and Management
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    • v.5 no.5 s.21
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    • pp.183-192
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    • 2004
  • Even in Korea the number of steel structure buildings that allow internal space and easy change of their layouts in accordance with the purpose of buildings and box-type steel bridges constructed with thick plates with thickness in a rage just from a few $\beta$AE to \$100\beta$AE is increasing these days and therefore, domestic fabrication and processing technology of members for steel structures is being improved at a pace faster than in the past to meet the growing requirements of consumers for high reliability on quality control on the related steel structures. However, most domestic fabricators os steel structures who are turning out their steel products in accordance with the designs prepared by engineering companies in their respective works for the sake of cost cut more than anything else, hesitating to introduce any advanced new technology into themselves. In the case of the steel structure design application for small and mid-size buildings in particular, it is quite meaningful not only for those who are involved in steel structure business, but also for the people working at construction work fields to review the result of the study on the connections of steel structure members deigned to obtain superb quality of steel structures within short period for steel fabrication and erection at fields in economical ways, as there is a glowing tendency seeking standardization of connection of steel structure members as well as whole structure together with the development on design of construction system of buildings including their exterior and interior decoration materials, manufacture of the related members and fabrication technique structure. This paper has been prepared with the aim to review the peculiar characteristics of buildings constructed with the main frames of steel structures and actual cases of the change made ing the connections between steel structure columns and between columns and girder members in order to reduce the work period necessary for fabrication and erection of steel structures at the maximum as well as the some examples of steel structures fabricated through automatic welding by robots for box-type columns in addition to the description of the problems found in the course of fabricating those steel structures, suggesting possible counter-measures to solve them.

Determination and Survey of Fluoroquinolones Residue in Chicken Muscle by HPLC with Fluorescence Detector (액체크로마토그래피-형광검출기를 이용한 닭고기 중 플루오로퀴놀론계 항균물질 정량분석 및 잔류조사)

  • 박은정;임지흔;이성모
    • Journal of Food Hygiene and Safety
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    • v.19 no.1
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    • pp.12-18
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    • 2004
  • Ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin in chicken muscle were seperated by liquid extraction and determined with high performance liquid chromatography (HPLC) with fluorescence detector. Analysis was carried out using following conditions; Cl8 column (250${\times}$4.6 mm i.d. 5 ${\mu}{\textrm}{m}$ particle size), mobile phase composed of D.W. (containing 0.4% triethylamine and phospholic acid): methanol : acetonitrile (800:100:100, v/v/v), isocratic pump at a flow rate of 1.0 $m\ell$/min and 50 ${mu}ell$ of injection volume, fluorescence detector with EX278 nm/EM.456 nm. The calibration curves of four fluoroquinolones showed linearity (${\gamma}$$^2$$\geq$0.999) at concenration range of 0.025-0.6 $\mu\textrm{g}$/ml. The recoveries in fortified chicken muscle represented more than 80% with low coefficient of variation (〈10%) for concentration range of four fluoroquinolones. The detection limits for ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin were 23.5, 3.4, 3.0 and 2.5 ng/g in chicken muscle, respectively. We also monitored fluoroquinolones residue in muscle of chickens (broiler 1:227, Korean native chicken 219, laying chicken 77) using EEC-4-plate screening and HPLC conformation methods. Ten(broiler 5, Korean native chicken 5) out of the fifteen samples which were positively detected by EEC-plate screening method from 1,523 chicken meat were confirmed with ciprofloxacin and enrofloxacin by HPLC. The ranges of residual concentration were 0-0.12 ppm for ciprofloxacin and 0.01-6.79 ppm for enrofloxacin. In conclusion, our method could be applied effectively to determine four fluoroquinolones residues in chicken meat, and further survey for fluoroquinolones residue in chicken meat are needed for more effective control of fluoroquinolones used in livestock.

Purification and Characterization of Sulfated Polysaccharide Isolated from Hot Water Extract of Pachymeniopsis elliptica (Pachymeniopsis elliptica의 열수 추출물로부터 분리한 함황 다당류의 정제 및 특성)

  • Lee, Sun-Hee;Jun, Woo-Jin;Yu, Kwang-Won;Chun, Hyug;Shin, Dong-Hoon;Hong, Bum-Shik;Cho, Hong-Yon;Yang, Han-Chul
    • Korean Journal of Food Science and Technology
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    • v.32 no.5
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    • pp.1191-1197
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    • 2000
  • In the preliminary study, we investigated the anti-complementary activities of 62 extracts from Korean edible seaweeds. Of those, Pachymeniopsis elliptica showed the highest anti-complementary activity. Therefore, it was purified as follows; i) PE-1 by ethanol precipitation, ii) PE-1-C by ultrafiltration, iii) PE-1-CIV by DEAE-Toyopearl 650C, and iv) PE-1-CIV-ii by Sepharose CL-6B. The purified compound, PE-1-CIV-ii, was the complexed homogeneous polysaccharide (molecular mass: 780 kDa) with 82.9% of anti-complementary activity. Also, it contained a significant amount of sulfate group (30.5%), which indicated it as a sulfated algal polysaccharide. Its structural monosaccharides were galactose (44.3%), 3,6-anhydrogalactose (34.0%), glucose (8.2%), fucose (5.4%), xylose (5.2%) and rhamnose (2.9%). After the treatment of periodate on a sample, a significant decrease in anti-complementary activity was found, which was a characteristic of bioactive polysaccharides. And-tumor activity of PE-1-A, B and C was tested in the sarcoma-180 solid tumor model. The PE-1-C with the largest molecular mass (more than 300 kDa) showed 81% of inhibition on the solid tumors, suggesting that the anti-complementary activity was, at least in part, related to anti-tumor activity. Based upon these results, the purified polysacchardes could be an immunopotentiator in vivo.

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Estimation of TROPOMI-derived Ground-level SO2 Concentrations Using Machine Learning Over East Asia (기계학습을 활용한 동아시아 지역의 TROPOMI 기반 SO2 지상농도 추정)

  • Choi, Hyunyoung;Kang, Yoojin;Im, Jungho
    • Korean Journal of Remote Sensing
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    • v.37 no.2
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    • pp.275-290
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    • 2021
  • Sulfur dioxide (SO2) in the atmosphere is mainly generated from anthropogenic emission sources. It forms ultra-fine particulate matter through chemical reaction and has harmful effect on both the environment and human health. In particular, ground-level SO2 concentrations are closely related to human activities. Satellite observations such as TROPOMI (TROPOspheric Monitoring Instrument)-derived column density data can provide spatially continuous monitoring of ground-level SO2 concentrations. This study aims to propose a 2-step residual corrected model to estimate ground-level SO2 concentrations through the synergistic use of satellite data and numerical model output. Random forest machine learning was adopted in the 2-step residual corrected model. The proposed model was evaluated through three cross-validations (i.e., random, spatial and temporal). The results showed that the model produced slopes of 1.14-1.25, R values of 0.55-0.65, and relative root-mean-square-error of 58-63%, which were improved by 10% for slopes and 3% for R and rRMSE when compared to the model without residual correction. The model performance by country was slightly reduced in Japan, often resulting in overestimation, where the sample size was small, and the concentration level was relatively low. The spatial and temporal distributions of SO2 produced by the model agreed with those of the in-situ measurements, especially over Yangtze River Delta in China and Seoul Metropolitan Area in South Korea, which are highly dependent on the characteristics of anthropogenic emission sources. The model proposed in this study can be used for long-term monitoring of ground-level SO2 concentrations on both the spatial and temporal domains.

LC-MS/MS analysis and anti-inflammatory effects of crude extract from Coptidis Rhizoma (황련 추출물의 LC-MS/MS 분석 및 항염증 효과)

  • Min-Jung, Kim;Ye-Jin, Yang;Kwang-Youn, Kim;Hun Hwan, Kim;Jae Dong, Son;Ju-Hye, Yang;Dong bin, Lee;Woo Hyun, Kim;Hu-Jang, Lee;Seon Been, Bak;Kwang-Il, Park
    • Herbal Formula Science
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    • v.31 no.1
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    • pp.1-10
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    • 2023
  • Objectives : The main aim of this study was to examine the LC-MS/MS used to identify phenolic compounds of CRE(Coptidis Rhizoma 70% EtOH Extract). Also, we investigated antioxidative activities and Anti-inflammatory activities. Methods : LC-MS/MS Analysis HPLC and LC-MS/MS were performed on a 1260 series HPLC system (Agilent Technologies, Inc., California, USA) and 3200 QTrap tandem mass system (Sciex LLC) operated in positive ion mode (spray voltage set at -4.5 kV). The solvent used was DW and Acetonitrile containing 0.1% formic acid, a gradient system was used at a flow rate of 0.5 mL/min for analysis, and a Prontosil C18 column (length, 250 mm; inner diameter, 4.6 mm; particle size, 5 ㎛; Phenomenex Co., Ltd., California, USA, Biochoff Chromatography) was used. The solvent conditions used in the mobile phases were 0-10 min at 10-15% B, 10-20 min at 20% B, 20-30 min at 25%, 30-40 min at 40%, 40-50 min at 70%, 50-60 min at 95%, and 60-70 min at 95%. The analysis was performed at a wavelength of 284 nm and a temperature of 35℃. The cell viability was measured using a 3-(4,5-dimethyethiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity. We examined the effects of CRE on the lipopolysaccharide (LPS)-induced production of nitric oxide (NO) in a RAW 264.7 cells Results : The chemical analysis CRE by Liquid chromatography-tandem mass spectrometry (LC-MS/MS) confirmed that Rosmarinic acid, Ferrulic acid, 3-O-feruloylquinic acid, and 5-O-feruloylquinic acid as phenolic components. DPPH radical scavenging activity was the inhibitory activity of CRE showed at 200 ㎍/mL a statistically significant level. MTT assay demonstrated that the CRE did not have a cytotoxic effect in RAW 264.7 and LPS-induced RAW264.7 cells. Also, CRE reduced NO production in RAW 264.7 cells stimulated with LPS. Conclusions : Based on these findings, The chemical analysis 4 major components CRE such as Rosmarinic acid, Ferrulic acid, 3-O-feruloylquinic acid, and 5-O-feruloylquinic acid. Moreover, we confirmed that CRE has effects antioxidant and anti-inflammatory. The results demonstrate that CRE can be used as an antioxidant and a powerful chemopreventive ingredient against inflammatory diseases.

A study on the field tests and development of quantitative two-dimensional numerical analysis method for evaluation of effects of umbrella arch method (UAM 효과 평가를 위한 현장실험 및 정량적 2차원 수치해석기법 개발에 관한 연구)

  • Kim, Dae-Young;Lee, Hong-Sung;Chun, Byung-Sik;Jung, Jong-Ju
    • Journal of Korean Tunnelling and Underground Space Association
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    • v.11 no.1
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    • pp.57-70
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    • 2009
  • Considerable advance has been made on research on effect of steel pipe Umbrella Arch Method (UAM) and mechanical reinforcement mechanism through numerical analyses and experiments. Due to long analysis time of three-dimensional analysis and its complexity, un-quantitative two-dimensional analysis is dominantly used in the design and application, where equivalent material properties of UAM reinforced area and ground are used, For this reason, development of reasonable, theoretical, quantitative and easy to use design and analysis method is required. In this study, both field UAM tests and laboratory tests were performed in the residual soil to highly weathered rock; field tests to observe the range of reinforcement, and laboratory tests to investigate the change of material properties between prior to and after UAM reinforcement. It has been observed that the increase in material property of neighboring ground is negligible, and that only stiffness of steel pipe and cement column formed inside the steel pipe and the gap between steel pipe and borehole contributes to ground reinforcement. Based on these results and concept of Convergence Confinement Method (CCM), two dimensional axisymmetric analyses have been performed to obtain the longitudinal displacement profile (LDP) corresponding to arching effect of tunnel face, UAM effect and effect of supports. In addition, modified load distribution method in two dimensional plane-strain analysis has been suggested, in which effect of UAM is transformed to internal pressure and modified load distribution ratios are suggested. Comparison between the modified method and conventional method shows that larger displacement occur in the conventional method than that in the modified method although it may be different depending on ground condition, depth and size of tunnel, types of steel pipe and initial stress state. Consequently, it can be concluded that the effect of UAM as a beam in a longitudinal direction is not considered properly in the conventional method.

Design and Implementation of MongoDB-based Unstructured Log Processing System over Cloud Computing Environment (클라우드 환경에서 MongoDB 기반의 비정형 로그 처리 시스템 설계 및 구현)

  • Kim, Myoungjin;Han, Seungho;Cui, Yun;Lee, Hanku
    • Journal of Internet Computing and Services
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    • v.14 no.6
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    • pp.71-84
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    • 2013
  • Log data, which record the multitude of information created when operating computer systems, are utilized in many processes, from carrying out computer system inspection and process optimization to providing customized user optimization. In this paper, we propose a MongoDB-based unstructured log processing system in a cloud environment for processing the massive amount of log data of banks. Most of the log data generated during banking operations come from handling a client's business. Therefore, in order to gather, store, categorize, and analyze the log data generated while processing the client's business, a separate log data processing system needs to be established. However, the realization of flexible storage expansion functions for processing a massive amount of unstructured log data and executing a considerable number of functions to categorize and analyze the stored unstructured log data is difficult in existing computer environments. Thus, in this study, we use cloud computing technology to realize a cloud-based log data processing system for processing unstructured log data that are difficult to process using the existing computing infrastructure's analysis tools and management system. The proposed system uses the IaaS (Infrastructure as a Service) cloud environment to provide a flexible expansion of computing resources and includes the ability to flexibly expand resources such as storage space and memory under conditions such as extended storage or rapid increase in log data. Moreover, to overcome the processing limits of the existing analysis tool when a real-time analysis of the aggregated unstructured log data is required, the proposed system includes a Hadoop-based analysis module for quick and reliable parallel-distributed processing of the massive amount of log data. Furthermore, because the HDFS (Hadoop Distributed File System) stores data by generating copies of the block units of the aggregated log data, the proposed system offers automatic restore functions for the system to continually operate after it recovers from a malfunction. Finally, by establishing a distributed database using the NoSQL-based Mongo DB, the proposed system provides methods of effectively processing unstructured log data. Relational databases such as the MySQL databases have complex schemas that are inappropriate for processing unstructured log data. Further, strict schemas like those of relational databases cannot expand nodes in the case wherein the stored data are distributed to various nodes when the amount of data rapidly increases. NoSQL does not provide the complex computations that relational databases may provide but can easily expand the database through node dispersion when the amount of data increases rapidly; it is a non-relational database with an appropriate structure for processing unstructured data. The data models of the NoSQL are usually classified as Key-Value, column-oriented, and document-oriented types. Of these, the representative document-oriented data model, MongoDB, which has a free schema structure, is used in the proposed system. MongoDB is introduced to the proposed system because it makes it easy to process unstructured log data through a flexible schema structure, facilitates flexible node expansion when the amount of data is rapidly increasing, and provides an Auto-Sharding function that automatically expands storage. The proposed system is composed of a log collector module, a log graph generator module, a MongoDB module, a Hadoop-based analysis module, and a MySQL module. When the log data generated over the entire client business process of each bank are sent to the cloud server, the log collector module collects and classifies data according to the type of log data and distributes it to the MongoDB module and the MySQL module. The log graph generator module generates the results of the log analysis of the MongoDB module, Hadoop-based analysis module, and the MySQL module per analysis time and type of the aggregated log data, and provides them to the user through a web interface. Log data that require a real-time log data analysis are stored in the MySQL module and provided real-time by the log graph generator module. The aggregated log data per unit time are stored in the MongoDB module and plotted in a graph according to the user's various analysis conditions. The aggregated log data in the MongoDB module are parallel-distributed and processed by the Hadoop-based analysis module. A comparative evaluation is carried out against a log data processing system that uses only MySQL for inserting log data and estimating query performance; this evaluation proves the proposed system's superiority. Moreover, an optimal chunk size is confirmed through the log data insert performance evaluation of MongoDB for various chunk sizes.