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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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Geometry Design of a Pitch Controlling Type Horizontal Axis Turbine and Comparison of Power Coefficients (피치각 제어형 수평축 조류 터빈의 형상설계 및 출력계수 비교)

  • Park, Hoon Cheol;Truong, Quang-Tri;Phan, Le-Quang;Ko, Jin Hwan;Lee, Kwang-Soo;Le, Tuyen Quang;Kang, Taesam
    • Journal of the Korean Society for Marine Environment & Energy
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    • v.17 no.3
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    • pp.167-173
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    • 2014
  • In this work, based on the blade element-momentum theory (BEMT), we proposed the geometry of a lab-scale horizontal axis tidal turbine with a diameter of 80cm, which can demonstrate the maximum power coefficient, and investigated the effect of blade pitch angle increase on the power coefficient. For validation of the computed power coefficients by the BEMT, we also computed the power coefficient using the computational fluid dynamics (CFD) for each case. For the CFD, 15 times of the turbine radius was used for the length and diameter of the computational domain, and the open boundary condition was prescribed at the boundary of the computational domain. The maximum power coefficients of the turbine acquired by the BEMT and CFD were about 48%, showing a good agreement. Both of the power coefficients computed by the BEMT and CFD tended to decrease when the blade pitch angle increases. The two power coefficients for a given tip-speed ratio were in good agreement. Through the present study, we have confirmed that we can trust the proposed geometry and the computed power coefficients based on the BEMT.

Feedback Phenomenon in Technology Art (예술 공학의 피드백)

  • Kim Hyung-Gi
    • Science of Emotion and Sensibility
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    • v.8 no.4
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    • pp.423-433
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    • 2005
  • The computer hardware development has provided many chances of emergence between art and technology. In many cases today's interactive artworks cannot be completed without audience's participation. The interactive production process with technical supplementation can be celled feedback. Mr. Nam Jun Paik showed 'Participant TV' that interacts with audience's response in real time. It means artwork changes with the constantly changing value from the data set from human visual perception. Dan Graham showed another feedback related work, which delays 5second playback in mirror that implies consequence of time. Today's media art has to sublimate coincidence, time ant audience into philosophical artwork through consonance that comes with video and sound as we can see from Bill Viola. Stelarc produced artworks. That use input data that is weak signals from brain, muscles. Through a terminal display with player, body expanded meaning of media. Jeffrey Shaw's 'Legible City' provided a fabrication of the reality with the interaction of bicycle's pedal speed and steering direction that is controlled by 4river. RE:MARK used microphone as input device as Edmond Couchot's 'Je same a la vent' and Nam Jun Paik's 'Participant TV' did. There is no communication without feedback between human being. The reality makes audience involved into artworks. That is the reason why feedback has to be natural. Through the feedback process, the originality of the idea is altered by audience. The feedback is not just part of flesh of artwork rather skeleton of it. Technological showoff cannot be art itself The perfection of technological application plan helps feedback that interacts with audience naturally in order that audience hoes not feel the feedback as artificial plan. Interactive media art has to be evolved into new media form with new integration feedback technology.

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Geostatistical Integration Analysis of Geophysical Survey and Borehole Data Applying Digital Map (수치지도를 활용한 탄성파탐사 자료와 시추조사 자료의 지구통계학적 통합 분석)

  • Kim, Hansaem;Kim, Jeongjun;Chung, Choongki
    • Journal of the Korean GEO-environmental Society
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    • v.15 no.3
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    • pp.65-74
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    • 2014
  • Borehole investigation which is mainly used to figure out geotechnical characterizations at construction work has the benefit that it provides a clear and convincing geotechnical information. But it has limitations to get the overall information of the construction site because it is performed at point location. In contrast, geophysical measurements like seismic survey has the advantage that the geological stratum information of a large area can be characterized in a continuous cross-section but the result from geophysics survey has wide range of values and is not suitable to determine the geotechnical design values directly. Therefore it is essential to combine borehole data and geophysics data complementally. Accordingly, in this study, a three-dimensional spatial interpolation of the cross-sectional distribution of seismic refraction was performed using digitizing and geostatistical method (krigring). In the process, digital map were used to increase the trustworthiness of method. Using this map, errors of ground height which are broken out in measurement from boring investigation and geophysical measurements can be revised. After that, average seismic velocity are derived by comparing borehole data with geophysical speed distribution data of each soil layer. During this process, outlier analysis is adapted. On the basis of the average seismic velocity, integrated analysis techniques to determine the three-dimensional geological stratum information is established. Finally, this analysis system is applied to dam construction field.

Phase Behavior of Simvastatin Drug in Mixtures of Dichloromethane and Supercritical Carbon Dioxide and Microparticle Formation of Simvastatin Drug Usins Supercritical Anti-Solvent Process (디클로로메탄과 초임계 이산화탄소의 혼합용매에서 Simvastatin 약물의 상거동과 초임계 역용매 공정을 이용한 Simvastatin 약물 미세입자의 제조)

  • Oh, Dong-Joon;Lee, Byung-Chul
    • Clean Technology
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    • v.13 no.1 s.36
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    • pp.34-45
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    • 2007
  • Phase behavior of the ternary systems of water-insoluble simvastatin drug, which is well known to be effective drugs for hypercholesterolemia therapy, in solvent mixtures of dichloromethane and supercritical carbon dioxide was investigated to present a guideline of establishing operating conditions in the particle formation of the drugs by a supercritical anti-solvent recrystallization process utilizing dichloromethane as a solvent and carbon dioxide as an anti-solvent. The solubilities of simvastatin in the mixtures of dichloromethane and carbon dioxide were determined as functions of temperature, pressure and solvent composition by measuring the cloud points of the ternary mixtures at various conditions using a high-pressure phase equilibrium apparatus equipped with a variable-volume view cell. The solubility of the drug increased as the dichloromethane composition in solution and the system pressure increases at a fixed temperature. A lower solubility of the drug was obtained at a higher temperature. The second half of this work is focused on the particle formation of the simvastatin drug by a supercritical anti-solvent recrystallization process in a cylindrical high-pressure vessel equipped with an impeller. Microparticles of the simvastatin drug were prepared as functions of pressure (8 MPa to 12 MPa), temperature (303.15 K, 313,15 K), feed flow rate of carbon dioxide, and stirring speed (up to 3000 rpm), in order to observe the effect of those process parameters on the size and shape of the drug microparticles recrystallized.

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Research about Imaginary Line Extension Application in Composition of TV News - With Special Quality of Imaginary Line in Focus - (TV News 영상구성에서 Imaginary Line 확대 적용에 관한 연구 - 이미지너리 라인의 특성을 중심으로 -)

  • Lim, Pyung-Jong;Kwak, Hoon-Sung
    • The Journal of the Korea Contents Association
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    • v.8 no.9
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    • pp.55-65
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    • 2008
  • At these information age when the importance of news is of particular emphasis, the field of image-production for the news are being made rapid progressive by high-tech like multi-media, multi-channel digital system. Even experts who have engaged in the work of broadcasting in th field for a long time are perplexed with rapid development in Broadcasting equipments and expression techniques. The field of TV is characterized by the speed of change and the desire of viewers for new and interesting video images. The image expression system applying image line has ever existed as one of conventional image expression methods. Obsolete and old image expressions are paling into significance for viewers who want to access more information in a short time. but The change of image expression systems due to the progressive stream of time has forced existing imaginary to be changed constantly to accommodate the changing interests and expectations of the viewers. Therefore, in this treatise, we need a broad interpretation about the direction of this imaginary line for TV news image in that existing systems of image producing haven’t also been changed and adapted to the stream of time. In these days, image is defined as not only video, but also audio. also We need to reduce the confusion concerning the imaginary line and contribute to a correct understanding images of TV news for not only customers but also producer by extending and applying the concept of imaginary line to image producing.

The Management of Fish Culture Industry and the Role of Fisheries Cooperatives in Japan;- Focused on Yellowtail Cultural industry - (일본에 있어서 어류양식업의 경영과 어협의 역할;(방어양식경영을 중심으로))

  • 최정윤
    • The Journal of Fisheries Business Administration
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    • v.25 no.2
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    • pp.1-46
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    • 1994
  • The Purpose of this research is to analyze and discuss the development of yellowtail aquaculture industry in Japan and its management structure. The research includes the following : (a) It confirms the industrial conditions of yellowtail aqaculture which has a national technical and mass production system that has been developed at great speed. (b) It analyzes yellowtail aqaculture development from a family - oriented management to a large scale production. (c) It examines how the fisheries cooperatives harmonized their role with the object of individual aqaculture management and aqaculture fishing ground management. The reasons for this study focusing on the yellowtail aqaculture industry of Japan are : (a) The yellowtail aqaculture is regared as a typical field in aqaculture because it reflects the general aqaculture history, quantity of fisheries aqaculture product, the number of fishermen involved in this industry, technology , and the live and fish market formation in Japan. (b) The aqaculture has the most powerful entrepreneurial in financial and management style. The aqaculture industry also has a most individual management style which includes planned production and shipping strategy. This research has attempted to study the industrial processes of fisheries aqaculture industry and its management development, and focused on the yellowtail aqaculture industry of Japan. This work also includes data about the aqaculture management of fisheries cooperatives and case by case analysis of aqaculture production. The following results were obtained from this study : First, even though ocean, weather conditions, and widespread propagation of places suitable for aqaculture in Japan were crucial factors in aqaculture development, it must be pointed out that fisheries policy in Japan changed from "catching" in the 1960s to "cultivating". Second, the widespread course of fisheries cultivating technology in Japan has had two characteristics. One is that early aqaculture technology spread to the southern part of Japan and the other is that the metal nets were widely used in the northern part in the 1970s. Japan's yellowtail aqaculture industry's overproduction was due to metal nets. However, the use of mwtal nets also contributed to the improvement of aqaculture and the strategic aspects of aqaculture management. In addition, it should be stressed that Kagoshima prefecture as the pioneer of metal nets contributed to fisheries aqaculture development in japan. Third, as aqaculture technology developed, entrepreneurial qualities of aqaculture management also developed this field into a large scale business. Even though it is not clear, large scale management of yellowtail aqaculture shows evidence of superiority over small andmedium - size management of yellowtail aqaculture. Fourth, yellowtail aqaculture management in Japan hascontributed to the production system and aqaculture strategy to meet consumers' needs and market demands from weather - oriented trational fisheries industry, which overcame their overproduction structure. Fifth, Japanese fisheries cooperative played very important roles in the prevention of fishing grounds production from destruction and in promoting suitable aqaculture facilities so that aqaculture could grow continually.ld grow continually.

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A 14b 100MS/s $3.4mm^2$ 145mW 0.18um CMOS Pipeline A/D Converter (14b 100MS/s $3.4mm^2$ 145mW 0.18un CMOS 파이프라인 A/D 변환기)

  • Kim Young-Ju;Park Yong-Hyun;Yoo Si-Wook;Kim Yong-Woo;Lee Seung-Hoon
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.43 no.5 s.347
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    • pp.54-63
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    • 2006
  • This work proposes a 14b 100MS/s 0.18um CMOS ADC with optimized resolution, conversion speed, die area, and power dissipation to obtain the performance required in the fourth-generation mobile communication systems. The 3-stage pipeline ADC, whose optimized architecture is analyzed and verified with behavioral model simulations, employs a wide-band low-noise SHA to achieve a 14b level ENOB at the Nyquist input frequency, 3-D fully symmetric layout techniques to minimize capacitor mismatch in two MDACs, and a back-end 6b flash ADC based on open-loop offset sampling and interpolation to obtain 6b accuracy and small chip area at 100MS/s. The prototype ADC implemented in a 0.18um CMOS process shows the measured DNL and INL of maximum 1.03LSB and 5.47LSB, respectively. The ADC demonstrates a maximum SNDR and SFDR of 59dB and 72dB, respectively, and a power consumption of 145mW at 100MS/s and 1.8V. The occupied active die area is $3.4mm^2$.

A 12b 100MS/s 1V 24mW 0.13um CMOS ADC for Low-Power Mobile Applications (저전력 모바일 응용을 위한 12비트 100MS/s 1V 24mW 0.13um CMOS A/D 변환기)

  • Park, Seung-Jae;Koo, Byeong-Woo;Lee, Seung-Hoon
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.47 no.8
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    • pp.56-63
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    • 2010
  • This work proposes a 12b 100MS/s 0.13um CMOS pipeline ADC for battery-powered mobile video applications such as DVB-Handheld (DVB-H), DVB-Terrestrial (DVB-T), Satellite DMB (SDMB), and Terrestrial DMB (TDMB) requiring high resolution, low power, and small size at high speed. The proposed ADC employs a three-step pipeline architecture to optimize power consumption and chip area at the target resolution and sampling rate. A single shared and switched op-amp for two MDACs removes a memory effect and a switching time delay, resulting in a fast signal settling. A two-step reference selection scheme for the last-stage 6b FLASH ADC reduces power consumption and chip area by 50%. The prototype ADC in a 0.13um 1P7M CMOS technology demonstrates a measured DNL and INL within 0.40LSB and 1.79LSB, respectively. The ADC shows a maximum SNDR of 60.0dB and a maximum SFDR of 72.4dB at 100MS/s, respectively. The ADC with an active die area of 0.92 $mm^2$ consumes 24mW at 1.0V and 100MS/s. The FOM, power/($f_s{\times}2^{ENOB}$), of 0.29pJ/conv. is the lowest of ever reported 12b 100MS/s ADCs.

A Real-Time Data Transfer Mechanism Considering Link Error Rates in Wireless Sensor Networks (무선 센서 네트워크에서 링크 에러율을 고려한 실시간 데이터 전달 기법)

  • Choi, Jae-Won;Lee, Kwang-Hui
    • Journal of the Institute of Electronics Engineers of Korea TC
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    • v.44 no.1
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    • pp.146-154
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    • 2007
  • In this paper, we have presented a real-time transfer mechanism for the delay-sensitive data in WSNs (Wireless Sensor Networks). The existing methods for real-time data transfer select a path whose latency is shortest or the number of hops is least. Although the approaches of these methods are acceptable, they do not always work as efficiently as they can because they had no consideration for the link error rates. In the case of transmission failures on links, they can not guarantee the end-to-end real-time transfer due to retransmissions. Therefore, we have proposed an algorithm to select a real-time transfer path in consideration of the link error rates. Our mechanism estimates the 1-hop delay based on the link error rate between two neighboring nodes, which in turn enables the calculation of the expected end-to-end delay. A source node comes to choose a path with the shortest end-to-end delay as a real-time route, and sends data along the path chosen. We performed various experiments changing the link error rates and discovered that this proposed mechanism improves the speed of event-to-sink data transfer and reduces delay jitter. We also found that this mechanism prevents additional energy consumption and prolongs network lifetime, resulting from the elative reduction of transmission failures and retransmissions.