• Toxicological Research
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• 제20권3호
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• pp.195-203
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• 2004

4-Tert-Octylphenol (OP) is a surfactant additive widely used in the manufacture of a variety of detergents and plastic products. OP can disrupt endocrine function in humans and animals. This study was carried out to obtain toxicokinetic parameters of OP in male Sprague-Dawley (SD) rats. Male rats were administered with OP by single oral application of 200 mg/kg body weight. Blood, urine and tissues samples were taken at several time intervals after administration. Analysis of samples for OP was performed by column-switching high performance liquid chromatography (HPLC). In addition, we exam-ined tissue distribution and accumulation of OP after single oral application of 50, 100, and 200 mg/kg, single intravenous injection of 1, 5 and 10 mg/kg or daily application of 50 mg/kg for 14 consecutive days. After single oral administration of 200 mg/kg, Cmax of 213 $\pm$ 123 ng/ml was reached within the first 1.3 hr (Tmax) in the plasma. AUC was calculated for 1,333$\pm$484 ngㆍhr/ml. The final elimination half-life of plasma was longer than that of urine, but urinary clearance was lower than oral. A very small fraction of OP (Fe < 0.0017%) was excreted in urine within 24 hr. These results indicated that the major excretion route of OP was not urine. The mean maximal tissue distribution of OP was obserbed at 6 hr after treatment and slowly decreased time-dependently. High OP concentrations were detected in fat at 24 hr. The OP in fat was slowly released with longer elimination half-life and lower clearance than that of other tissues. OP was not accumulated in the liver following single oral application but 14-day oral treatments resulted in two-fold accumulation. It was probably due to the saturation of detoxification pathways. On the other hand, the mRNA expression of cytochrome P450 isoforms except CYP2C11 was not affected by OP at any dose. The expression of CYP2C11 mRNA decreased in a dose-dependent manner. This result suggests that OP changes expression of the male-specific cytochrome P450 isoforms in rat liver, and these changes are closely related to the toxic and estrogenic effect of OP.

• Biomolecules & Therapeutics
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• 제9권4호
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• pp.291-297
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• 2001

The bioequivalence of two triflusal products was evaluated with 20 healthy volunteers following single oral dose according to the guidelines of Korea Food and Drug Administration (KFDA). Trisa $l^{R}$ capsule (Whanin Pharm. Corp., Korea) and Disgre $n^{R}$ capsule (Myung-In Pharm. Corp., Korea) were used as test product and reference product, respectively. Both products contain 300 mg of trifusal. One capsule of test product or reference product was orally administered to the volunteers, respectively, by randomized two period crossover study (2$\times$2 Latin square method). Blood samples were taken at predetermined time intervals for 4 hours and the determination of trifusal was accomplished using semi-microbore HPLC equipped with automated column switching system. The analytical method with HPLC was validated according to the Bioanalytic Method Validation guideline by F7A prior to determining the plasma samples. The pharmacokinetic parameters (AU $C_{0-4h}$ $C_{max}$ and $T_{max}$) were calculated and ANOVA test was utilized for statistical analysis of parameters. As a result of the assay validation, the limit of quantification of trifusal in human plasma by current assay procedure was 50 ng/ml using 500 $\mu$l of plasma. The accuracy of the assay was from 97.76% to 116.51% while the intra-day and inter-day coefficient of variation of the same concentration range was less than 15%. Average drug concentration at the designated time intervals and pharmacokinetic parameters calculated were not significantly different between two products (p>0.05). The difference of mean AU $C_{olongrightarrow4hr}$, $C_{max}$, and $T_{max}$ between the two products (2.92, 4.39, and -2.44%, respectively) were less than 20%. The power (1-$\beta$) and treatment difference ($\Delta$) for AU $C_{olongrightarrow4hr}$ and $C_{max}$ were more than 0.8 and less than 0.2, respectively. Although the power for $T_{max}$ was under 0.8, $T_{max}$ of the two products was not significantly different from each other (p>0.05). These results satisfied the criteria of KFDA guideline for bioequivalence, indicating the two products of triflusal were bioequivalent.quivalent.ent.ent.

• 한국환경보건학회지
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• 제34권4호
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• pp.271-278
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• 2008

Dialkylated phthalates have been commonly used as plasticizers and a variety of applications. Phthalate diesters have been shown to be developmental and reproductive toxicants. It is very difficult to exactly estimate the dose of dialkylated phthalates taken up by the general population because of environmental contamination. Urinary metabolites of phthalates enabled to estimate internal exposure. The objective of this study was quantitative determination of phthalate metabolites by LC/MS/MS with on-line cleanup method to analyze phthalate metabolites in Korean children's urine. We employed LC/MS/MS with on-line enrichment and column-switching techniques for this biological monitoring. Metabolites determined were 4 primary metabolites; MEHP, MnBP, MiBP, MEP and 2 secondary metabolites of DEHP; 5-OH-MEHP), 5-oxo-MEHP. We analyzed children's urine from 30 boys and 30 girls. The method detection limit of phthalate metabolites were 0.03 ng/mL for MEP, 1.05 ng/mL for MBP, 0.22 ng/mL for MEHP, 0.15 ng/mL for 5-OHMEHP and 0.16 ng/mL for 5-oxo-MEHP, respectively. Switching Column LC/MS/MS was proven to be a useful tool to determine metabolites of phthalate diesters in human urine. The correlation among phthalate metabolites was very high and statistically significant, except MEP. The children's age (months) was negatively correlated to the concentration of phthalate metabolites. The geometric mean concentration of phthalate metabolites (mg/g creatinine) in children's urine were 25.5 for MEP, 130.3 for MnBP, 56.8 for MiBP, 19.5 for MEHP, 85.6 for 5-OH-MEHP and 83.1 for 5-oxo-MEHP, respectively. Levels of estimated daily intake of parent phthalate compounds (${\mu}g$/kg bw/day) were 0.8 for DEP, 5.0 for DnBP, 1.9 for DiBP and $8.9{\sim}14.2$ for DEHP, respectively. Estimated daily intake for DEP and DiBP were lower than those of other studies but the value for DEHP was higher than that of other study.

• 한국전산구조공학회논문집
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• 제22권4호
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• pp.307-314
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• 2009

본 논문은 기하학적 비선형성을 가진 보존적 단일 하중 매개변수의 탄성 상태 공간구조의 탄성 분기 좌굴해석을 위한 공간프레임의 정식화, 분기경로 추적을 위한 pin-pointing 및 분기경로 전환알고리즘을 기술하고 있다. 복잡한 좌굴 후 거동특성을 파악하기 위한 본 연구의 공간프레임요소는 오일러리안 좌표계에 의한 유한회전이론으로 강체변형을 계산하였고, 굽힘효과가 고려된 보-기둥식을 적용하여 적은 개수의 요소의 사용으로도 정해를 얻을 수 있도록 하였으며, 후좌굴해석과 같은 고도의 비선형해석을 수행하기 위해 기하강성행렬의 모멘트에 대한 영향을 고려하였다. 분기좌굴에 의한 좌굴후 평형상태인 주경로와 분기경로의 pin-pointing 알고리즘으로 특이점을 계산하였으며, 고유치 및 고유모드를 이용한 본 연구의 수치알고리즘에 의해 분기경로를 추적하였다. 분기좌굴 해석예제로 평면프레임, 평면아치 및 공간돔에 대한 분기좌굴 해석을 수행하여 본문에서 제시한 수치해석법의 정확성 및 적용성을 검증한다.

• 한국광학회지
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• 제16권3호
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• pp.287-294
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• 2005

본 논문에서는 크로스(CROSS) 포트에 광섬유 지연선로가 연결된 $2\times2$ 광 스위치들로 구성된 광섬유 지연선로 행렬과 다파장 광원을 이용한 2차원 위상 배열 안테나(Phased Array Antenna; PAA)용 광 실시간 지연선로(True Time-Delay ; TTD)의 구조를 제안하였고, 파장 의존형 광 TTD와 파장 비의존형 광 TTD를 결합하여 10-GHz 2차원 PAA용 2-비트$\times$4-비트 광 TTD를 제작하였다. 단위 시간 지연 차이가 각각 ${\Delta}T=12ps$와 $\Delta\tau=6ps$인 파장 의존형 광 TTD와 파장 비의존형 광 TTD의 모든 주사각에 대해서 시간지연을 측정하였다. 파장 의존형 광 TTD의 시간 지연 오차는 지터에 의해 최대 2.8 ps가 발생하였으며, 파장 비의존형 광 TTD의 경우에는 ${\pm}0.8ps$이하의 오차가 나타났다. 제안된 2차원 PAA용 광 TTD의 구조는 1차원 선형 PAA보다 높은 이득을 얻을 수 있고, 다파장 광원을 사용하므로 광 파워 및 파장의 안정성을 확보할 수 있으며, 전기적 스위치 제어기를 이용하여 $2\times2$ 광 스위치 행렬을 열(column) 단위로 절체하기 때문에 주사 빔 제어 속도가 빠르고 구동이 간단한 장점을 갖고 있다.

• 한국정보통신학회논문지
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• 제15권4호
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• pp.913-920
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• 2011

본 논문에서는 수동형 900MHz RFID 태그 칩용 로직 공정 기반 저면적.저전력 1Kb EEPROM를 설계하였다. 1Kb 셀 배열 (cell array)은 1 워드 (word)의 EEPROM 팬텀 셀 (phantom cell)을 2차원 배열 형태인 (16행 ${\times}$ 16열) ${\times}$ 4블록으로 구성하였으며, 4개의 메모리 블록이 CG (Control Gate)와 TG (Tunnel Gate) 구동회로를 공유하므로 저면적 IP 설계를 하였다. TG 구동회로를 공유하기 위해 소자간의 전압을 신뢰성이 보장되는 5.5V 이내로 유지하면서 동작 모드별 TG 바이어스 전압을 스위칭해 주는 TG 스위치 회로를 제안하였다. 그리고 4 메모리 블록 중 하나의 블록만 활성화하는 partial activation 방식을 사용하므로 읽기 모드에서 전력소모를 줄였다. 그리고 하나의 열 (column)당 연결되는 셀의 수를 줄이므로 읽기 모드에서 BL (Bit-Line)의 스위칭 시간을 빠르게 하여 액세스 시간 (access time)을 줄였다. Tower $0.18{\mu}m$ CMOS 공정을 이용하여 (32행 ${\times}$ 16열) ${\times}$ 2블록과 (16행 ${\times}$ 16열) ${\times}$ 4블록의 2가지 배열 형태의 1Kb EEPROM IP를 설계하였으며, (16행 ${\times}$ 16열) ${\times}$ 4블록의 IP가 (32행 ${\times}$ 16열) ${\times}$ 2블록의 IP에 비해 레이아웃 면적은 11.9% 줄였으며, 읽기 모드 시 전력소모는 51% 줄였다.

• 한국독성학회:학술대회논문집
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• 한국독성학회 2006년도 추계학술대회
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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.

• Food Science and Biotechnology
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• 제17권2호
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• pp.262-266
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• 2008

This study was conducted to provide a vitamin $B_{12}$ database for the representative Korean food items and to assess the dietary intake assessment of vitamin $B_{12}$ for Koreans. The vitamin $B_{12}$ content of 106 foods had been determined by high performance liquid chromatography (HPLC) using column switching method. Rich sources of vitamin $B_{12}$ were meats, milk, and egg ($0.3-3.4\;{\mu}g/100g$). Vegetables and fruits contained vitamin $B_{12}$ below limit of detection (LOD). The major food sources for vitamin $B_{12}$ intake were milk (72.0%), meats (22.3%), egg (3.6%), and fishes & shellfishes (2.1%). Mean vitamin $B_{12}$ intake of Koreans was $3.16\;{\mu}g$/person/day. The proportion of population with intake below estimate average requirement (EAR) and above recommended intake (RI) of vitamin $B_{12}$ was 60.7 and 36.5%, respectively. The vitamin $B_{12}$ intake level of young children with 1-2 years which was 834.6% of RI while the intake level of the older adults 50 years and older was only 70.0% of RI. Also, there were regional differences between urban and rural area. The population with intake below RI was larger than that with intake above RI in Korea.

• JSTS:Journal of Semiconductor Technology and Science
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• 제8권2호
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• pp.128-133
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• 2008

Phase-change random access memory (PRAM) chip cell phase of amorphous state is rapidly changed to crystal state above 160 Celsius degree within several seconds during Infrared (IR) reflow. Thus, on-board programming method is considered for PRAM chip programming. We demonstrated the functional 512Mb PRAM with 90nm technology using several novel core circuits, such as metal-2 line based global row decoding scheme, PN-diode cells based BL discharge (BLDIS) scheme, and PMOS switch based column decoding scheme. The reverse-state standby current of each PRAM cell is near 10 pA range. The total leak current of 512Mb PRAM chip in standby mode on discharging state can be more than 5 mA. Thus in the proposed BLDIS control, all bitlines (BLs) are in floating state in standby mode, then in active mode, the activated BLs are discharged to low level in the early timing of the active period by the short pulse BLDIS control timing operation. In the conventional sense amplifier, the simultaneous switching activation timing operation invokes the large coupling noise between the VSAREF node and the inner amplification nodes of the sense amplifiers. The coupling noise at VSAREF degrades the sensing voltage margin of the conventional sense amplifier. The merit of the proposed sense amplifier is almost removing the coupling noise at VSAREF from sharing with other sense amplifiers.

• 화약ㆍ발파
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• 제28권1호
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• pp.19-26
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• 2010

이 논문은 필리핀 석회석 광산에 적용한 연구 결과로서 이 광산에서는 파쇄석 입도분포가 좋지 않고 벽면의 유지나 파쇄석 더미의 분산이 불량하였다. 기폭패턴을 대각선 방식에서 V 타입으로 바꾸고 전색장을 조정하여 저항과 가스압의 유지기간을 향상시켰다. 이를 통하여 발파결과가 향상되었다. 특히 공당발파영역이 넓어진 것으로써 그 성과를 확인할 수 있다. 공당발파영역은 기존의 $8.96m^2$에서 $12m^2$로 넓어졌다. 화약계수는 증가하였고 대괴의 수는 감소하였으며, 전방적재기의 행정시간이 감소하였다. 또 공전 시간이 줄었으며 적재높이가 향상되었다.