Kang Mi Kyung;Ahn Mee Ryung;Chung Hye Joo;Choi Sun Ok;Choi Hong Serk;Yang Ji Sun;Lee Yong Bok;Yoo Tae Moo;Sohn Soo Jung
Toxicological Research
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v.20
no.3
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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.
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.
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.
Journal of the Computational Structural Engineering Institute of Korea
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v.22
no.4
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pp.307-314
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2009
The present paper briefly describes the space frame element and the fundamental strategies in computational elastic bifurcation theory of geometrically nonlinear, single load parameter conservative elastic spatial structures. A method for large deformation(rotation) analysis of space frame is based on an eulerian formulation, which takes into consideration the effects of large joint translations and rotations with finite deformation(rotation). The local member force-deformation relationships are based on the beam-column approach, and the change in member chord lengths caused by axial strain and flexural bowing are taken into account. and the derived geometric stiffness matrix is unsymmetric because of the fact that finite rotations are not commutative under addition. To detect the singular point such as bifurcation point, an iterative pin-pointing algorithm is proposed. And the path switching mode for bifurcation path is based on the non-negative eigen-value and it's corresponding eigen-vector. Some numerical examples for bifurcation analysis are carried out for a plane frame, plane circular arch and space dome structures are described.
In this paper, an optical true time-delay (TTD) for two-dimensional (2-D) phased array antennas (PAAs), composed of a multi-wavelength optical source and a fiber optic delay line matrix consisting of $2\times2$ optical switches with optical fiber connected between cross ports, has been proposed. A 2-bit $\times4-bit$ optical TTD for 10-GHz 2-D PAAs has been implemented by cascading a wavelength dependent TTD (WD-TTD) and a wavelength independent TTD (WI-TTD). The unit time delay for WD-TTD and WI-TTD have been chosen as ${\Delta}T=12ps$ and $\Delta\tau=6ps$, respectively. Time delay have been measured at all radiation angles. The maximum delay error for WD-TTD was measured to be 3 ps due to jitter incurred from gain switching. For the case of WI-TTD, error was within ${\pm}\;1\;ps$. The proposed optical TTD for a 2-D PAA has the following advantages: 1) higher gain compared to one-dimensional linear PAAs, 2) stabilization of optical power and wavelength by using a multi-wavelength optical source, and 3) fast beam scan and simple operation due to electronic control of the $2\times2$ optical switches matrix on a column-by-column basis.
Journal of the Korea Institute of Information and Communication Engineering
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v.15
no.4
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pp.913-920
/
2011
In this paper, a logic process based 1-kbit EEPROM IP for RFID tag chips of 900MHz is designed. The cell array of the designed 1-kbit EEPROM IP is arranged in a form of four blocks of 16 rows x 16 columns, that is in a two-dimensional arrangement of one-word EEPROM phantom cells. We can reduce the IP size by making four memory blocks share CG (control gate) and TG (tunnel gate) driver circuits. We propose a TG switch circuit to supply respective TG bias voltages according to operational modes and to keep voltages between devices within 5.5V in terms of reliability in order to share the TG driver circuit. Also, we can reduce the power consumption in the read mode by using a partial activation method to activate just one of four memory blocks. Furthermore, we can reduce the access time by making BL (bit line) switching times faster in the read mode from reduced number of cells connected to each column. We design and compare two 1-kbit EEPROM IPs, two blocks of 32 rows ${\times}$ 16 columns and four blocks of 16 rows ${\times}$ 16 columns, which use Tower's $0.18{\mu}m$ CMOS process. The four-block IP is smaller by 11.9% in the layout size and by 51% in the power consumption in the read mode than the two-block counterpart.
Proceedings of the Korean Society of Toxicology Conference
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2006.11a
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pp.65-74
/
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.
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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v.8
no.2
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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.
The paper presents a case study of a limestone quarry of the Philippines, where major problems in terms of improper fragmentation, poor wall control, and poor heave of the muck pile were witnessed. The paper highlights the significant role of switching over from diagonal firing pattern to V-type firing pattern, and also of making suitable adjustments in the stemming column length for improved confinement and gas retention. The study revealed that by making aforesaid design modifications in the blast round, marked improvement in blasting results was registered. Looking at the results, it was further contemplated to expand the mesh area in the subsequent blast rounds. The mesh area was incremented from the existing $8.96m^2$ to $12m^2$. The results were meticulously registered in the field, and clearly depicted definite improvements in the blast results in terms of increased P.F., reduced boulder count, reduced FEL cycle time, reduced dozing hours and improved heave.
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