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Full validation of high-throughput bioanalytical method for the new drug in plasma by LC-MS/MS and its applicability to toxicokinetic analysis

  • Han, Sang-Beom
    • Proceedings of the Korean Society of Toxicology Conference
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    • 2006.11a
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    • pp.65-74
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    • 2006
  • Modem drug discovery requires rapid pharmacokinetic evaluation of chemically diverse compounds for early candidate selection. This demands the development of analytical methods that offer high-throughput of samples. Naturally, liquid chromatography / tandem mass spectrometry (LC-MS/MS) is choice of the analytical method because of its superior sensitivity and selectivity. As a result of the short analysis time(typically 3-5min) by LC-MS/MS, sample preparation has become the rate- determining step in the whole analytical cycle. Consequently tremendous efforts are being made to speed up and automate this step. In a typical automated 96-well SPE(solid-phase extraction) procedure, plasma samples are transferred to the 96-well SPE plate, internal standard and aqueous buffer solutions are added and then vacuum is applied using the robotic liquid handling system. It takes only 20-90 min to process 96 samples by automated SPE and the analyst is physically occupied for only approximately 10 min. Recently, the ultra-high flow rate liquid chromatography (turbulent-flow chromatography)has sparked a huge interest for rapid and direct quantitation of drugs in plasma. There is no sample preparation except for sample aliquotting, internal standard addition and centrifugation. This type of analysis is achieved by using a small diameter column with a large particle size(30-5O ${\mu}$m) and a high flow rate, typically between 3-5 ml/min. Silica-based monolithic HPLC columns contain a novel chromatographic support in which the traditional particulate packing has been replaced with a single, continuous network (monolith) of pcrous silica. The main advantage of such a network is decreased backpressure due to macropores (2 ${\mu}$m) throughout the network. This allows high flow rates, and hence fast analyses that are unattainable with traditional particulate columns. The reduction of particle diameter in HPLC results in increased column efficiency. use of small particles (<2 urn), however, requires p.essu.es beyond the traditional 6,000 psi of conventional pumping devices. Instrumental development in recent years has resulted in pumping devices capable of handling the requirements of columns packed with small particles. The staggered parallel HPLC system consists of four fully independent binary HPLC pumps, a modified auto sampler, and a series of switching and selector valves all controlled by a single computer program. The system improves sample throughput without sacrificing chromatographic separation or data quality. Sample throughput can be increased nearly four-fold without requiring significant changes in current analytical procedures. The process of Bioanalytical Method Validation is required by the FDA to assess and verify the performance of a chronlatographic method prior to its application in sample analysis. The validation should address the selectivity, linearity, accuracy, precision and stability of the method. This presentation will provide all overview of the work required to accomplish a full validation and show how a chromatographic method is suitable for toxirokinetic sample analysis. A liquid chromatography/tandem mass spectrometry (LC-MS/MS) method developed to quantitate drug levels in dog plasma will be used as an example of tile process.

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Automated Silhouette Extraction Method for Generating a Blueprint from 3D Scan Data of Cultural Asset (문화재의 3D 스캔 데이터로부터 도면을 생성하기 위한 자동화된 실루엣 추출 방법)

  • Jung, Jung-Il;Cho, Jin-Soo;WhangBo, Tae-Keun
    • The Journal of the Korea Contents Association
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    • v.8 no.12
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    • pp.10-19
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    • 2008
  • In this paper, we propose an automated silhouette extraction method that can effectively extract inner-patterns and silhouettes from 3D scan data of cultural asset. First of all, after creating the edge list of 3D vector data, we decide contour edge and crease edge according to viewpoint. In the next step, after extracting surface silhouette by investigating the vector variation of adjacent faces in crease edge, we finally extract the contour silhouette and surface silhouette for generating the blueprint of cultural asset. To evaluate the performance of the proposed silhouette extraction method, we performed experiments of silhouette extraction using a traditional tile model, a car model and a stone monument model. Comparing with the conventional threshold-based silhouette extraction method, the proposed method extracted more distinct and clear surface silhouettes and inner-patterns by effectively removing meaningless edges, such as noise.

An Economic Approach to the Rational Development and Use of Marine Resources (II) (해양자원의 합리적 개발.이용에 관한 경제학적 연구(II))

  • 유동운
    • The Journal of Fisheries Business Administration
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    • v.14 no.1
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    • pp.19-43
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    • 1983
  • Mankind has made traditional use of various ocean resources in such several forms as fish, plants food, means of transportation, and military purpose, followed by the recent exploitation of offshore subsoil or sea-bed minerals, energies, and utilization of ocean space. These available ocean resources come from the marine natural environment which has a distinct feature in view of the relationship between human wants and their capacity to meet them. Though these socially basic resources however bring forth the so-called scarcity or differential rent, their communal nature of ownership dissipates free gifts of nature endowed to society as a whole. Thus to maximize these rents and social welfare thereof, rents should be secured and preserved through a well-defined arrangements of property-ownership as well as appropriate comparison of competing uses of marine resources, taking full cognizance of their irreversible adverse effects of a specific choice on the alternatives. Here I showed the sources of rent yielded from the multiple uses of navigation, fishery, mariculture, minerals, and recreation site, and also summarized the presently widely-known analytic tool to measure these rents with emphasis on due care of the telescopic faulty of the appraiser in charge, viewed from the communal point, Finally, as communal property is in strict sense owned by the public at large, notwithstanding the restricted communal ownership at government or local governments control, effectiveness of competition I expect should be kept while transferring claims of these resources from the legal owner to private enterprise as well as while extracting their rent by her. In particular, various national or social objectives look forward to tile maximization of social efficiency. Discretionary system in noncompetitive method thus, is exceptionally suggested because of probable suspicion from the public whether these resources are transferred as a give away or not in discretion. And these realized rent payments, I propose, should be wisely taken advantage of in advancement of scientific research in marine nature to bring an incremental rent therefrom successively.

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A Segmentation Method for Counting Microbial Cells in Microscopic Image

  • Kim, Hak-Kyeong;Lee, Sun-Hee;Lee, Myung-Suk;Kim, Sang-Bong
    • Transactions on Control, Automation and Systems Engineering
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    • v.4 no.3
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    • pp.224-230
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    • 2002
  • In this paper, a counting algorithm hybridized with an adaptive automatic thresholding method based on Otsu's method and the algorithm that elongates markers obtained by the well-known watershed algorithm is proposed to enhance the exactness of the microcell counting in microscopic images. The proposed counting algorithm can be stated as follows. The transformed full image captured by CCD camera set up at microscope is divided into cropped images of m$\times$n blocks with an appropriate size. The thresholding value of the cropped image is obtained by Otsu's method and the image is transformed into binary image. The microbial cell images below prespecified pixels are regarded as noise and are removed in tile binary image. The smoothing procedure is done by the area opening and the morphological filter. Watershed algorithm and the elongating marker algorithm are applied. By repeating the above stated procedure for m$\times$n blocks, the m$\times$n segmented images are obtained. A superposed image with the size of 640$\times$480 pixels as same as original image is obtained from the m$\times$n segmented block images. By labeling the superposed image, the counting result on the image of microbial cells is achieved. To prove the effectiveness of the proposed mettled in counting the microbial cell on the image, we used Acinetobacter sp., a kind of ammonia-oxidizing bacteria, and compared the proposed method with the global Otsu's method the traditional watershed algorithm based on global thresholding value and human visual method. The result counted by the proposed method shows more approximated result to the human visual counting method than the result counted by any other method.

Archaeometric Characteristics of Roof Tiles in Baekje Kingdom from the Danjiri Site of Gongju, Korea (공주 단지리유적 출토 백제 기와의 고고과학적 특성)

  • Jang, Sung-Yoon;Lee, Chan-Hee;Park, Dae-Sun
    • Journal of Conservation Science
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    • v.22
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    • pp.15-30
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    • 2008
  • The roof tiles from the tomb in Baekje Kingdom of the Danjiri site in Gongju, Korea were studied for the production techniques and raw material provenance based on archaeometric characteristics. The roof tiles had traditional shapes of Baekje Kingdom, which show flow texture on the surfaces and sections with the roof tiles of hard or soft-type. These roof tiles were locally produced, using refining soils according to mineralogical and geochemical characteristics. Also roof tiles were divided to 2 groups by firing temperature and physical properties. One of them had soft with porous texture and fired probably about 700 to $900^{\circ}C$. The other had hard with vitrified texture and probably fired about 940 to $1,020^{\circ}C$. Buried for long time and used as a tomb, roof tiles had experienced chemical alteration due to the enrichments of trace elements abundant in human tissues.

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A Study on the Architectural of Jae-sil in Jeonalbukdo (전라북도 재실 건축에 관한 연구)

  • Lee, Sang-Sun;Shin, Woong-Ju
    • Journal of the Korean Institute of Rural Architecture
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    • v.15 no.4
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    • pp.35-42
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    • 2013
  • The study aims to investigate general characteristics of Jae-sil from an architectural perspective by grasping location, deployment, structure, and plan composition based on existing inhabited conditions in Jeollabukdo. Results derived from the study are as follows. First, the location of Jae-sil is classified into mountainous and village types, and the two types showed a similar distribution. The village type showed the most distribution in the foot of a mountain in the rear of village, while the mountainous type is close to graveyard. The Jae-sil were mostly exposed to south, southeast, and southeast, which was not significantly different from residence. For deployment of the Jae-sil, a "二" shaped house, where main quarter and gated building are parallel located, can be common, indicating that additional attached building is less required. Second, for the platform out of structural components, coursed masonry was conducted by using natural rocks, and placed were a prop on the platform, first line on processed foot stone, and others on natural foot stone. For pillar, front line round columns, while others square columns. The binding type of the upper part of pillar is dominated by jangyeosujang and sorosujang. For wooden frame structure, 5ryangs were the most distributed, and out of these, 1goju 5ryang was the most generally used. For a roof part, it was composed with gambrel roof with single eave, and the roof was constructed by placing traditional Korean tile roof on the top. Third, for a size of Jae-sil out of plan composition, although the facade and the side of it were presented in a diverse manner, 4 facade rooms and 1.5 side rooms were the most frequently presented, and all Jae-sil were equipped with front ceremonial space. For spatial composition of Jae-sil, main floored hall is placed at the center, and each room is placed on the left and right side to secure space for ancestral rite for participants of it, and for a house with 5 rooms or more, it shows that main floored hall and rooms are weighted from side to side.

House Type and Household Structures of South Kyongsang Province in the Enlightenment Period (『가호안』 분석을 통해 본 개화기 경상남도의 가옥형태와 구조)

  • 최영준
    • Journal of the Korean Geographical Society
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    • v.39 no.3
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    • pp.297-320
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    • 2004
  • Household Register of South Kyongsang Province compiled by the Korean government in 1904 keeps complete details on local houses of eleven out of a total of thirty-one counties in the district. This study examines, band on e analysis of the primary source materials, e specifics of traditional housing of South Kyongsang Province with special reference to the magnitude of housing lots, size of dwellings, land and house ownership, and distribution of thatch and tile roof houses by dong, myon and county. Findings from the survey of the household register suggest that approximately 20 percent of households were established on the private or rented public lands, that 90 percent resided in undersized housing with just one or two rooms besides a kitchen, and that the regional average of dwelling size was no bigger than 2.75 rooms. The fact clarifies that the three-room thatch houses prevailed in South Kyongsang Province about a century ago. The miserable living conditions were tranalated into a constricted personal space of 2 to 4 square meters and a small-size household of less than 4 family members.

The Quality Characteristics of Imported and Korean Chicken Breast Meats in Korean Market (국내시장에 유통중인 수입산 및 한국산 닭고기 가슴육의 품질 특성)

  • 김일석;민중석;이상옥;박광순;김중완;김방현;최일신;이무하
    • Food Science of Animal Resources
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    • v.21 no.4
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    • pp.300-306
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    • 2001
  • This study was carried out to compare the quality of imported chicken breast meats with domestic esse. In the proximate analysis. Thai chicken breast meats showed the highest content of tile crude protein(P<0.001), and the lowest contents of the crude fat and moisture. KAB(breast meat purchased at Korean traditional market) were higher. In total plate counts and in E. coli than other (P<0.001). and showed the highest TBARS value. In the descriptive analysis for the fresh meats. Thai chicken showed the highest acceptability score. In the results of cooked meat. KAB showed the highest acceptability score.

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A study on the Chronological Recordings and construction method of Wooden Pagoda Sites of Baekjae (백제(百濟) 목탑지(木塔地) 편년(編年)과 축기부(軸基部) 축조기법(築造技法)에 관한 연구(硏究))

  • Cho, Weon-Chang
    • Journal of architectural history
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    • v.17 no.4
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    • pp.65-82
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    • 2008
  • The wooden pagoda sites which have been confirmed in Baekjae's former territory so far have flattened surface of the earth or foundation pert made by digging up the earth. In particular, the latter is found more often in the pagoda sites of Baekjae, which is essential and absolutely necessary because of the characteristics of pagoda structure. The wooden pagoda sites with foundation part made by digging up the earth under the stylobate are found at Yongjeongli ruined temple site of Woongjin area, and at Neung-sa temple site, Wangheung-sa temple site, Geumgang-sa temple site, and Mireuk-sa temple site of Sabi period. They are also observed at Hwanglyong-sa nine-storied wooden pagoda of Shilla and at Biin five-storied stone pagoda of early Goryeo. They are important data improving that the construction technologies of Baekjae continued to be applied to build stone or wooden pagodas, transcending time and space. Recently, the site assumed as a wood pagoda site of Hanseong area was examined in Gyeongdang sect ion of Pungnap mud fortification. If this is proved to be a real wooden pagoda site, this digging-up construction technology of foundation part ann be concluded to be a traditional engineering technology of Baekjae which was frequently used from Hanseong period to Sabi period. On the other hand, this digging-up construction technology of foundation part has been found only at pagoda sites and main building sites of temple ruins, and it helps examine their symbolism.

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THE TASTE COMPOUNDS OF BROILED DRIED SEA MUSSELS (배건담치의 정미성분에 관한 연구)

  • RYU Byeong-Ho;LEE Eung-Ho
    • Korean Journal of Fisheries and Aquatic Sciences
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    • v.11 no.2
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    • pp.65-83
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    • 1978
  • This study was attempted to evaluate the taste of broiled-dried sea mussel which is a traditional dried Sea food in Korea. The contents of such compounds as free amino acids, nucleotides and their related compounds, TMAO, betaine, and nonvolatile organic acids were analysed. From the results of analysis of nucleotides, the contents of AMP and ADP in broiled-dried Mytilus coruscus and Mytilus edulis appeared higher than other nucleotides and tended to increase slightly after cooking, drying, and storage which might be due to both their stability and the addition of degradation of nucleic acids during cooking. In the free amino acid composition of fresh samples abundant amino were taurine, glycine, serine, glutamic acid, alanine, arginine, threonine, tyrosine, lysine and valine in order. Such amino acids as histidine, leucine, methionine and isoleucine were poor and both proline and phenylalanine were merely trace. The free amino acid composition in the extract of Mytilus corucus and Mytilus edulis after broil-drying was not changed. These amino acids, taurine, glycine, feline, glutamic acid, alanine and arginine were abundant in dried samples as well as in the fresh. The total free amino acid was greatly reduced after cooking and drying ranging from $76.3\%$ to $79.7\%$ loss to that of tile fresh. The content of betaine shelved the same tendency as in total free amino acid while TMA slightly increased relating to TMAO decrease during broil-frying. Such nonvolatile organic acids as succinic, lactic, malic and fumaric acid were abundant in both fresh and broiled-dried samples whereas oxalic and pyruvic acid were poor. It is found that the taste compounds of broiled-dried Mytilus coruscus and Mytilus edulis were composed of amino acids as glycine, serine, alanine, glutamic acid, arginine, and betaine, TMAO, ADP, AMP, and organic acids such as succinic acid, lactic acid, malic acid and fumaric acid. No significant differences in the taste compounds between male and female as well as between Mytilus coruscus and Mytilus edulis was not observed.

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