• 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.

• 전기전자학회논문지
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• 제12권3호
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• pp.176-183
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• 2008

본 논문에서는 DTMOS(Dynamic Threshold voltage MOSFET) 스위칭 소자를 사용한 고 효율 전원 제어 장치 (PMIC)를 제안하였다. 높은 출력 전류에서 고 전력 효율을 얻기 위하여 PWM(Pulse Width Modulation) 제어 방식을 사용하여 PMIC를 구현하였으며, 낮은 온 저항을 갖는 DTMOS를 설계하여 도통 손실을 감소시켰다. 벅 컨버터(Buck converter) 제어 회로는 PWM 제어회로로 되어 있으며, 삼각파 발생기(Saw-tooth generator), 밴드갭기준 전압 회로(Band-gap reference circuit), 오차 증폭기(Error amplifier), 비교기(Comparator circuit)가 하나의 블록으로 구성되어 있다. 삼각파 발생기는 그라운드부터 전원 전압(Vdd:3.3V)까지 출력 진폭 범위를 갖는 1.2MHz 발진 주파수를 가지며, 비교기는 2단 연산 증폭기로 설계되었다. 그리고 오차 증폭기는 70dB의 DC gain과 $64^{\circ}$ 위상 여유를 갖도록 설계하였다. Voltage-mode PWM 제어 회로와 낮은 온 저항을 스위칭 소자로 사용하여 구현한 DC-DC converter는 100mA 출력 전류에서 95%의 효율을 구현하였으며, 1mA이하의 대기모드에서도 높은 효율을 구현하기 위하여 LDO를 설계하였다.

• IMMUNE NETWORK
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• 제1권2호
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• pp.116-125
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• 2001

Background: Nitric oxide (NO) production has been described as a double-edged sword eliciting both pro- and anti-inflammatory effects in different immune reactions. This work was undertaken to investigate the immunoregulatory role of NO in experimental allergic encephalomyelitis (EAE) and experimental allergic uveitis (EAU). Method: We examined whether molsidomine (MSDM), a NO donor, administration to the myelin basic protein (MBP)- or interphotoreceptor retinoid binding protein (IRBP)-immunized rats could suppress EAE development by shifting toward the Th2 cytokine response. In the EAE experiments, the rats were treated orally with MSDM (10 mg/kg/day) at the early stage (-1~4 days) or throughout the experimental period (-1~15 days). Results: This resulted in significant amelioration of the disease and mild clinical symptoms, while MBP-immunization without MSDM administration showed severe EAE development. A marked reduction in inflammation was also observed in the spinal cord, indicating the crucial role of NO in the pathogenesis of EAE in in vivo. In the EAU experiments, a 24 h pre-treatment with MSDM prior to IRBP immunization resulted in significant inhibition of the disease. Furthermore, MSDM administration for 2 1 days completely reduced the incidence and severity of EAU. To investigate whether MSDM could modulate cytokine switching from Th 1 to Th2, culture supernatants of MBP- or IRBP-stimulated inguinal lymphocytes were analyzed. MSDM treatment enhanced IL-10 secretion but decreased IFN-${\gamma}$. IL-4 was undetectable in all groups. In contrast, the MBP-or IRBP-immunized rats without MSDM secreted high concentrations of IFN-${\gamma}$, but low concentrations of IL-10. Conclusion: In conclusion, NO administation suppresses EAE and EAU by modulating the Th1/Th2 balance during inflammatory immune responses. This work further suggests that NO may be useful in the therapeutic control of autoimmune disease.

• Asian Journal of Atmospheric Environment
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• 제5권3호
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• pp.146-151
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• 2011

1-Nitropyrene (1-NP), 2-NP and 2-nitrofluoranthene (2-NFR) are useful markers for studying the atmospheric behaviors of polycyclic aromatic hydrocarbons (PAHs) and nitropolycyclic aromatic hydrocarbons (NPAHs). However, present methods for measuring trace levels of these compounds are lesssensitive and laborious. Here we describe several improvements to a previously reported high-performance liquid chromatography-chemiluminescence detection system that allows it to determine trace levels of 1-, 2-NPs and 2-NFR. The proposed system was equipped with a reducer column packed with Pt/Rh instead of zinc whose life-time was limited. The combination of Cosmosil MS-II (monomeric ODS) and AR-II (polymeric ODS) columns was used instead of polymeric ODS columns as the separator column to improve the separation. An ethanol mixture with acetate buffer (pH 5.5) was used in place of an acetonitrile mixture with the same buffer to activate the reducer column. The same ethanol mixture was used as the mobile phase for the clean-up column. The switching time of the column switching valve was optimized to concentrate the amino-derivatives of above NPAHs quantitatively on the concentrator column. The concentrations of bis(2,4,6-trichlorophenly) oxalate and hydrogen peroxide in the chemiluminescence reagent solution were optimized to 0.4 mM and 30 mM, respectively, to increase the sensitivity. Under the above conditions, the detection limits (S/N=3) of 1-, 2-NPs and 2-NFR were 1 fmol (0.25 pg), 10 fmol (2.5 pg) and 4 fmol (1 pg), respectively. The proposed system was effectively used to determine trace levels of 1-, 2-NPs and 2-NFR in airborne particulates collected at Noto Peninsula. The atmospheric concentrations of 1-, 2-NPs and 2-NFR were not more than sub pg $m^{-3}$ levels. They were higher in winter (January) than in summer (July). In both seasons, the concentrations were in decreasing order, [2-NFR]>[1-NP]>[2-NP].

• 한국임상약학회지
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• 제20권3호
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• pp.235-241
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• 2010

Bambuterol hydrochloride, dimethylcarbamic acid 5-[2-(1,1-dimethylethyl)amino-1-hydroxyethyl]-1,3-phenylene ester hydrochloride, is the prodrug of active ${\beta}_2$-adrenergic metabolite terbutaline. The purpose of the present study was to evaluate the bioequivalence of two bambuterol hydrochloride tablets, $Bambec^{(R)}$ tablet 10 mg (Yuhan Co., Ltd.) and Bambucol tablet 10 mg (Sam Chun Dang Pharm. Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). In vitro release of bambuterol from two bambuterol hydrochloride formulations was tested using KP VIII Apparatus II method with various dissolution media. Twenty eight healthy male Korean volunteers, $23.86{\pm}1.65$ years in age and $68.98{\pm}9.58$ kg in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After two tablets containing 10 mg as bambuterol hydrochloride were orally administered, blood samples were taken at predetermined time intervals, and the concentrations of bambuterol in serum were determined using column switching HPLC with UV detector. The dissolution profiles of two formulations were similar in all tested dissolution media. The pharmacokinetic parameters such as $AUC_t$, $C_{max}$ and $T_{max}$ were calculated, and ANOVA test with K-BE Test 2002 was utilized for the statistical analysis of the parameters using logarithmically transformed $AUC_t$, $C_{max}$ and untransformed $T_{max}$. The results showed that the differences between two formulations based on the reference drug, $Bambec^{(R)}$, were -8.10%, -3.82% and 12.65% for $AUC_t$, $C_{max}$ and $T_{max}$, respectively. There were no sequence effects between two formulations in these parameters. The 90% confidence intervals using logarithmically transformed data were within the acceptance range of log 0.8 to log 1.25 (i.e., log 0.8093~log 1.0302 and log 0.8564~log 1.1280 for $AUC_t$ and $C_{max}$, respectively). Thus, the criteria of the KFDA bioequivalence guideline were satisfied, indicating Bambucol tablet 10 mg was bioequivalent to $Bambec^{(R)}$ tablet 10 mg.

• 한국정보디스플레이학회:학술대회논문집
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• 한국정보디스플레이학회 2008년도 International Meeting on Information Display
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• pp.993-994
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• 2008

Electrochromic (EC) devices are capable of reversibly changing their optical properties upon charge injection and extraction induced by the external voltage. The characteristics of the EC device, such as low power consumption, high coloration efficiency, and memory effects under open circuit status, make them suitable for use in a variety of applications including smart windows and electronic papers. Coloration due to reduction or oxidation of redox chromophores can be used for EC devices (e-paper), but the switching time is slow (second level). Recently, with increasing demand for the low cost, lightweight flat panel display with paper-like readability (electronic paper), an EC display technology based on dye-modified $TiO_2$ nanoparticle electrode was developed. A well known organic dye molecule, viologen, was adsorbed on the surface of a mesoporous $TiO_2$ nanoparticle film to form the EC electrode. On the other hand, ZnO is a wide bandgap II-VI semiconductor which has been applied in many fields such as UV lasers, field effect transistors and transparent conductors. The bandgap of the bulk ZnO is about 3.37 eV, which is close to that of the $TiO_2$ (3.4 eV). As a traditional transparent conductor, ZnO has excellent electron transport properties, even in ZnO nanoparticle films. In the past few years, one-dimension (1D) nanostructures of ZnO have attracted extensive research interest. In particular, 1D ZnO nanowires renders much better electron transportation capability by providing a direct conduction path for electron transport and greatly reducing the number of grain boundaries. These unique advantages make ZnO nanowires a promising matrix electrode for EC dye molecule loading. ZnO nanowires grow vertically from the substrate and form a dense array (Fig. 1). The ZnO nanowires show regular hexagonal cross section and the average diameter of the ZnO nanowires is about 100 nm. The cross-section image of the ZnO nanowires array (Fig. 1) indicates that the length of the ZnO nanowires is about $6\;{\mu}m$. From one on/off cycle of the ZnO EC cell (Fig. 2). We can see that, the switching time of a ZnO nanowire electrode EC cell with an active area of $1\;{\times}\;1\;cm^2$ is 170 ms and 142 ms for coloration and bleaching, respectively. The coloration and bleaching time is faster compared to the $TiO_2$ mesoporous EC devices with both coloration and bleaching time of about 250 ms for a device with an active area of $2.5\;cm^2$. With further optimization, it is possible that the response time can reach ten(s) of millisecond, i.e. capable of displaying video. Fig. 3 shows a prototype with two different transmittance states. It can be seen that good contrast was obtained. The retention was at least a few hours for these prototypes. Being an oxide, ZnO is oxidation resistant, i.e. it is more durable for field emission cathode. ZnO nanotetropods were also applied to realize the first prototype triode field emission device, making use of scattered surface-conduction electrons for field emission (Fig. 4). The device has a high efficiency (field emitted electron to total electron ratio) of about 60%. With this high efficiency, we were able to fabricate some prototype displays (Fig. 5 showing some alphanumerical symbols). ZnO tetrapods have four legs, which guarantees that there is one leg always pointing upward, even using screen printing method to fabricate the cathode.

• 대한전자공학회논문지SD
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• 제49권1호
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• pp.15-24
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• 2012

본 논문에서는 Switched-Capacitor 지연 기법의 새로운 고해상도 DPWM 발생기를 사용한 Dynamic-Response-Free SMPS를 제안한다. 제안된 회로는 Switched-Capacitor 지연 기법을 이용한 DPWM 발생기의 내부 커패시터 전압 기울기를 제어하는 방식으로 DPWM의 duty ratio를 결정한다. 제안된 회로는 컨버터의 피드백 전압과 기준전압을 비교하여 DPWM 발생기의 내부 캐패시터에 충방전되는 전류량을 제어하는 방식으로 출력전압 tracking이 가능하다. 따라서 제안된 회로는 기존 closed loop 제어 방식의 SMPS들에서 문제점이 되고 있는 동적 응답특성을 고려할 필요가 없으며, 출력 전압에 overshoot/undershoot로 인한 ringing 현상이 발생하지 않는다는 큰 장점을 가진다. 제안된 회로는 1MHz~10MHz까지 스위칭주파수를 사용자가 선택할 수 있으며, 100MHz의 내부 제어 동작 주파수로 10MHz 최대 스위칭 주파수(DPWM) 발생이 가능하다. 100MHz의 내부 제어 동작 주파수를 사용하여 10MHz 스위칭 주파수 발생시 소모되는 내부 회로의 최대 전류는 2.7mA이며, 출력 버퍼를 포함한 전체 시스템의 전류 소모는 15mA이다. 제안된 회로는 0.125%의 DPWM duty ratio 해상도를 가지고 부하에 최대 1A까지 전류공급이 가능하며, 최대 리플 전압은 8mV이다. 동부하이텍 BCD $0.35{\mu}m$ 공정 파라미터를 이용해 시뮬레이션을 수행하여 제안된 회로의 동작을 검증하였다.

• 한국정보통신학회논문지
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• 제10권3호
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• pp.486-495
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• 2006

본 논문에서 는 플래쉬 셀을 사용하여 수동형 UHF RFID 태그 칩에 사용되는 저전력 1Kb 동기식 EEPROM을 설계하였다. 저전력 EEPROM을 구현하기 위한 방법으로 다음과 같은 4가지 방법을 제안하였다. 첫째, VDD(=1.5V)와 VDDP(=2.5V)의 이중 전원 공급전압 방식을 사용하였고, 둘째, 동기식 회로 설계에서 클럭(clock) 신호가 계속 클럭킹(clocking)으로 인한 스위칭 전류(switching current)가 흐르는 것을 막기 위해 CKE(Clock Enable) 신호를 사용하였다. 셋째, 읽기 사이클에서 전류 센싱(current sensing) 방식 대신 저전력 소모를 갖는 clocked inverter를 사용한 센싱 방식을 사용하였으며, 넷째, 쓰기 모드시 Voltage-up 변환기(converter) 회로를 사용하여 기준전압 발생기(Reference Voltage Generator)에는 저전압인 VDD를 사용할 수 있도록 하여 전력 소모를 줄일 수가 있었다. $0.25{\mu}m$ EEPROM 공정을 이용하여 칩을 제작하였으며, 1Kb EEPROM을 설계한 결과 읽기 모드와 쓰기 모드 시에 소모되는 전력은 각각 $4.25{\mu}W$와 $25{\mu}W$이고, 레이아웃 면적(layout area)은 $646.3\times657.68{\mu}m^2$이다.

• 전자공학회논문지
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• 제50권11호
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• pp.70-77
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• 2013

본 논문에서는 새로운 기법의 PWM 발생기를 이용한 저면적, 고효율 SMPS를 제안한다. 제안된 회로에서 PWM의 duty ratio는 pseudo relaxation-oscillation technique를 이용한 PWM 발생기의 내부 커패시터 전압 기울기를 제어하는 방식으로 결정된다. 기존의 SMPS들에 비해, 제안된 제어 방식은 loop bandwidth 보상을 위해 기존의 아날로그 제어방식의 SMPS에서 요구되는 필터회로나 디지털 제어방식의 SMPS에서 요구되는 디지털 compensator가 필요 없기 때문에 단순한 구조로 구성된다. 또한, 제안된 회로는 PWM 발생기의 내부 캐패시터 용량 변화를 통해 1MHz~10MHz까지 스위칭 주파수를 사용자가 선택할 수 있다. 시뮬레이션 수행결과 제안된 SMPS는 10MHz 스위칭 주파수를 선택했을 때 내부회로에서 소모되는 전류는 최대 2.7mA, 파워 Trail을 제외한 전체 시스템의 전류 소모는 15mA였다. 또한, 제안된 SMPS는 시뮬레이션으로 3.3V출력에서 9mV의 최대 리플 전압이 발생하였다. 본 논문에서는 동부하이텍 BCD $0.35{\mu}m$ 공정 파라미터를 이용한 시뮬레이션 및 칩 테스트를 통해 제안된 회로를 검증하였다.

• 전자공학회논문지
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• 제54권6호
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• pp.65-71
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• 2017

디지털 이미지나 비디오는 저장, 전송을 하는 과정에서 여러 가지 종류의 잡음이 발생하게 된다. 이러한 잡음 중 Salt & Pepper 잡음은 원본 데이터를 훼손하여 압축 효율을 저하시키고 영상 처리 방법으로 이용하는 Edge Detection이나 Segmentation에서의 성능저하를 일으키는 요인이 된다. 이 잡음을 완화하기 위한 방법으로 Median Filter, Weighted Median Filter, Center Weighted Median Filter, Switching Weighted Median Filter, Adaptive Median Filter 등이 있다. 하지만 이러한 방법들은 높은 잡음의 밀도에서 성능이 다소 미흡하다. 따라서 본 논문에서는 Salt & Pepper 잡음이 발생하는 무선 통신 환경에서 잡음 완화를 위한 새로운 형태의 필터를 제안한다. 제안한 필터는 Salt & Pepper 잡음 감지를 통해 훼손된 픽셀의 위치를 확인하고 일정 영역의 훼손되지 않은 인접 픽셀 값들을 이용하여 잡음을 완화한다. 제안하는 필터 중 $3{\times}3$ 크기의 에러 마스크를 이용하는 필터의 성능을 기존의 방법들과 비교하여 PSNR을 통해 평가하였을 때, 이미지에서 잡음의 밀도가 95%일 때, MF와 비교하여 13.24 dB, AMF와 비교하여 13.09 dB의 성능을 향상시키는 것을 확인하였다.