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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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Reflective Bistable Chiral Splay Nematic Liquid Crystal Display (반사형 쌍안정 카이랄 스플레이 네마틱 액정표시소자)

  • Kim, Tae-Hyung;Lee, Joong-Ha;Shen, Zheng-Guo;Jang, Ji-Hyang;Kim, Jeong-Soo;Jhun, Chul-Gyu;Kwon, Soon-Bum;Yoon, Tae-Hoon;Kim, Jae-Chang
    • Korean Journal of Optics and Photonics
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    • v.22 no.1
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    • pp.23-29
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    • 2011
  • Bistable chiral splay nematic liquid crystal display (BCSN LCD) is a memory type liquid crystal display using splay and $-\pi$ twist states as two stable states. When the cell thickness to pitch (d/p) ratio is 0.25, splay and $-\pi$ twist states have permanent memory time. However, when the transition from $-\pi$ twist state to splay state is caused by a fringe field, pixel regions show that the splay state is not perfect, but rather includes a contribution from the $-\pi$ twist state. In this paper, we propose a reflective BCSN LCD using $-\pi$ twist state in which the two stable states do not coexist. The fabricated reflective BCSN LC cell shows a high contrast ratio of over 30:1 and response times of 950 ms and 450 ms in vertical and fringe field switching, respectively. The proposed cell also shows wide viewing angle characteristics of $180^{\circ}$ in left- and right directions.

Ferroelectric Properties of Pb[(Zr,Sn)Ti]N$bO_3$ Thin Films by Annealing (열처리에 따른 Pb[(Zr,Sn)Ti]N$bO_3$ 박막의 강유전 특성)

  • Choe, U-Chang;Choe, Hyeok-Hwan;Lee, Myeong-Gyo;Gwon, Tae-Ha
    • Journal of the Institute of Electronics Engineers of Korea SD
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    • v.38 no.7
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    • pp.473-478
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    • 2001
  • Ferroelectric P $b_{0.99}$[(Z $r_{0}$ 6S $n_{0.4}$)/0.9/ $Ti_{0.1}$]0.98/N $b_{0.02}$ $O_3$(PNZST) thin films were deposited by a RF magnetron sputtering on L $a_{0.5}$S $r_{0.5}$Co $O_3$(LSCO)/Pt/Ti/ $SiO_2$/Si substrate using a PNZST target with excess PbO of 10 mole%. The crystallinity and electrical properties of the thin films annealed at various temperature and time were investigated. The thin films deposited at the substrate temperature of 500 $^{\circ}C$ and the power of 80 W were crystallized to a perovskite phase after rapid thermal annealing(RTA). The thin films annealed at 650 $^{\circ}C$ for 10 seconds in air exhibited the good crystal structures. The remanent polarization and coercive field of the PNZST capacitor were about 20 $\mu$C/$\textrm{cm}^2$ and 50 kV/cm, respectively. The reduction of the polarization after 2.2$\times$10$^{9}$ switching cycles was less than 10 %..10 %......

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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.

The Inplementation of Fault-Tolerant Dual System Using the Hot-Standby Sparing Technique (핫 스탠바이 스페어링 기법을 이용한 고장 감내 이중화 시스템 설계)

  • Shin Jin wook;Park Dong sun
    • The Journal of Korean Institute of Communications and Information Sciences
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    • v.29 no.10A
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    • pp.1113-1122
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    • 2004
  • This paper is basically to achieve the high-availability and high-reliability of the control system from the implementation of the fault-tolerant system using the hot-standby sparing technique. To meet the objective, we design and implement a board with fault tolerance I/O bus to detect the fault. Warm-standby sparing technique is the fault tolerance technique usually used for switching control system in present. This technique can be easily implemented, but can not detect the fault quickly and can malfunction because of the hardware fault. The hot-standby sparing fault tolerant technique implemented in this paper is consists of dual processor modules and a I/O processor using fault tolerant I/O bus. The proposed method can find the faults as soon as possible, so it can prevent from wrong operation. Also it is possible to normal re-service due to the short recovering time. To implement the fault-tolerant dual system with fault detection be, two daughter, called FTMA and FTIA, boards designed and implemented are applied to the system. And we also simulated the proposed method to verify the high-availability and high-reliability of the control system using Markov process.

Suggestion of a Hybrid Method for Estimating Photovoltaic Power Generation (전력 IT 시스템에서 복합방식의 태양광 발전량 예측 방법 제안)

  • Ju, Woo-Sun;Jang, Min-Seok;Lee, Yon-Sik;Bae, Seok-Chan;Kim, Weon-Goo
    • Proceedings of the Korean Institute of Information and Commucation Sciences Conference
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    • 2011.10a
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    • pp.782-785
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    • 2011
  • Needs for MG(Microgrid) development are increasing all over the world as a solution to the problems including the depletion problem of energy resources, the growing demand for electric power and the climatic and environmental change. Especially Photovoltaic power is one of the most general renewable energy resources. However there is a problem of the uniformity of power quality because the power generated from solar light is very sensitive to climate fluctuation (variation of insolation and duration of sunshine, etc). As a solution to the above problem, ESS(Energy Storage System) is considered generally, but it has some limitations. To solve this problem this paper suggests a hybrid estimation method of photovoltaic power generation according to two climatic factors, i.e. insolation and sunshine. This result seems to help design the appropriate capacity of ESS and estimate the proper switching time between DC and AC power in the premises power system and thus maintain the uniformity of power quality.

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A New Mode Changable Asymmetric Full Bridge DC/DC Converter having 0 ~ 100 % Duty Ratio (0 ~ 100 % 시비율을 갖는 새로운 모드 가변형 비대칭 풀 브리지 DC/DC 컨버터)

  • Shin, Yong-Saeng;Roh, Chung-Wook;Hong, Sung-Soo;Han, Sang-Kyoo
    • The Transactions of the Korean Institute of Power Electronics
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    • v.15 no.2
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    • pp.103-110
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    • 2010
  • In this paper, a new mode changeable asymmetric full bridge dc/dc converter is proposed to solve the freewheeling current problem of the conventional zero voltage switching(ZVS) phase shift full bridge(PSFB) dc/dc converter of low output voltage and high output current applications. The proposed converter is operated as an asymmetric full bridge converter when the duty cycle is less than 50% and active clamp full bridge converter when the duty cycle is greater than 50%. As a result, since its freewheeling current is eliminated, the conduction loss is lower than that of the conventional ZVS PSFB dc/dc converter. Moreover, ZVS of all power switches can be ensured along a wide load ranges and output current ripple is very small. Therefore, high efficiency of the proposed converter can be achieved. Especially since its operation mode is changed to the active clamp full bridge converter during hold up time and can be operated with 50~100% duty ratio, it can produce the stable output voltage along wide input voltage range. The operational principles, theoretical analysis and design considerations are presented. To confirm the operation, validity and features of the proposed converter, experimental results from a 1.2kW($400V_{dc}/12V_{dc}$) prototype are presented.

Review of Safety Measures through Analysis of Accidents on the Vehicle-mounted MEWP(mobile elevated work platforms) (차량 탑재형 고소작업대의 사고분석을 통한 안전대책 고찰)

  • Lee, Junho
    • Journal of the Korea Institute of Construction Safety
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    • v.1 no.1
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    • pp.47-56
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    • 2018
  • In this paper, we analyze various cases of accidents caused by vehicle-mounted MEWPs(mobile elevated work platforms) which are most widely used for the high position level works, review the safety improvement measures for each of them, and propose basic data for the revision of related laws. The accidents by MEWPs were caused by the high level of works, which lead to fatal personnel accidents, so the measures for safety must be thoroughly carried out and the obligatory regulations by the related laws must be strictly observed. In this paper, we classify the cases of accidents at the workshop as 4 representative types and propose measures and remedies for them. According to the current regulations, it is possible to prepare for the accidents such as the wire rope breakage by switching to the all-chain drive method which does not have a daily use time limit instead of the wire rope drive method which is widely used at present. Also, it is suggested to add the daily use timetable to the nameplate attachment duty item according to the driving class.

Performance Verification of WAVE Communication Technology for Railway Application (차량용 무선통신기술(WAVE)의 철도 적용을 위한 성능검증)

  • Kim, Keum-Bee;Ryu, Sang-Hwan;Choi, Kyu-Hyoung
    • Journal of the Korean Society for Railway
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    • v.19 no.4
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    • pp.456-467
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    • 2016
  • Wireless Access in Vehicular Environments (WAVE) communication technology, which provides vehicleto-vehicle and vehicle-to-infrastructure communication and offers safe and convenient service, has been developed for application to an Intelligent Transport System (ITS). This paper provides field test results on a study of the feasibility of WAVE technology application to railway communication systems. A test railway communication system based on WAVE technology has been built along the Daebul line and a newly developed EMU. Field tests have been carried out according to the communication function requirements for LTE - R. The test results show that the railway communication system based on WAVE technology meets the functional requirements: maximum transmission length is 730m, maximum transfer delay is 5.69ms, and maximum interruption time is 1.36s; other tests including throughput test, video data transmission test, VoIP data test, and channel switching test also produced results that meets the functional requirements. These results suggest that WAVE technology can be applied to the railway communication system, enabling Vehicle-to-Wayside communication.

N-Acyl-Homoserine Lactone Quorum Sensing Switch from Acidogenesis to Solventogenesis during the Fermentation Process in Serratia marcescens MG1

  • Jin, Wensong;Lin, Hui;Gao, Huifang;Guo, Zewang;Li, Jiahuan;Xu, Quanming;Sun, Shujing;Hu, Kaihui;Lee, Jung-Kul;Zhang, Liaoyuan
    • Journal of Microbiology and Biotechnology
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    • v.29 no.4
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    • pp.596-606
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    • 2019
  • N-acyl-homoserine lactone quorum sensing (AHL-QS) has been shown to regulate many physiological behaviors in Serratia marcescens MG1. In the current study, the effects of AHL-QS on the biosynthesis of acid and neutral products by S. marcescens MG1 and its isogenic ${\Delta}swrI$ with or without supplementing exogenous N-hexanoyl-L-homoserine lactone ($C_6-HSL$) were systematically investigated. The results showed that swrI disruption resulted in rapid pH drops from 7.0 to 4.8, which could be restored to wild type by supplementing $C_6-HSL$. Furthermore, fermentation product analysis indicated that ${\Delta}swrI$ could lead to obvious accumulation for acidogenesis products such as lactic acid and succinic acid, especially excess acetic acid (2.27 g/l) produced at the early stage of fermentation, whereas solventogenesis products by ${\Delta}swrI$ appeared to noticeably decrease by an approximate 30% for acetoin during 32-48 h and by an approximate 20% for 2,3-butanediol during 24-40 h, when compared to those by wild type. Interestingly, the excess acetic acid produced could be removed in an AHL-QS-independent manner. Subsequently, quantitative real-time PCR was used to determine the mRNA expression levels of genes responsible for acidogenesis and solventogenesis and showed consistent results with those of product synthesis. Finally, by close examination of promoter regions of the analyzed genes, four putative luxI box-like motifs were found upstream of genes encoding acetyl-CoA synthase, lactate dehydrogenase, ${\alpha}$-acetolactate decarboxylase, and Lys-like regulator. The information from this study provides a novel insight into the roles played by AHL-QS in switching from acidogenesis to solventogenesis in S. marcescens MG1.