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New in vitro multiple cardiac ion channel screening system for preclinical Torsades de Pointes risk prediction under the Comprehensive in vitro Proarrhythmia Assay concepta

  • Jin Ryeol An;Seo-Yeong Mun;In Kyo Jung;Kwan Soo Kim;Chan Hyeok Kwon;Sun Ok Choi;Won Sun Park
    • The Korean Journal of Physiology and Pharmacology
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    • v.27 no.3
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    • pp.267-275
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    • 2023
  • Cardiotoxicity, particularly drug-induced Torsades de Pointes (TdP), is a concern in drug safety assessment. The recent establishment of human induced pluripotent stem cell-derived cardiomyocytes (human iPSC-CMs) has become an attractive human-based platform for predicting cardiotoxicity. Moreover, electrophysiological assessment of multiple cardiac ion channel blocks is emerging as an important parameter to recapitulate proarrhythmic cardiotoxicity. Therefore, we aimed to establish a novel in vitro multiple cardiac ion channel screening-based method using human iPSC-CMs to predict the drug-induced arrhythmogenic risk. To explain the cellular mechanisms underlying the cardiotoxicity of three representative TdP high- (sotalol), intermediate- (chlorpromazine), and low-risk (mexiletine) drugs, and their effects on the cardiac action potential (AP) waveform and voltage-gated ion channels were explored using human iPSC-CMs. In a proof-of-principle experiment, we investigated the effects of cardioactive channel inhibitors on the electrophysiological profile of human iPSC-CMs before evaluating the cardiotoxicity of these drugs. In human iPSC-CMs, sotalol prolonged the AP duration and reduced the total amplitude (TA) via selective inhibition of IKr and INa currents, which are associated with an increased risk of ventricular tachycardia TdP. In contrast, chlorpromazine did not affect the TA; however, it slightly increased AP duration via balanced inhibition of IKr and ICa currents. Moreover, mexiletine did not affect the TA, yet slightly reduced the AP duration via dominant inhibition of ICa currents, which are associated with a decreased risk of ventricular tachycardia TdP. Based on these results, we suggest that human iPSC-CMs can be extended to other preclinical protocols and can supplement drug safety assessments.

AN OPTIMUM DESIGN STUDY OF INTERLACING NOZZLE BY ANALYZING FLUID FLOW INSIDE INTERLACING NOZZLES

  • Juraeva Makhsuda;Ryu Kyung Jin;Kim Sang Dug;Song Dong Joo
    • 한국전산유체공학회:학술대회논문집
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    • 2005.10a
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    • pp.93-97
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    • 2005
  • Air interlacing serves to protect the yarn against damage, strengthens inter-filament compactness or cohesion, and ensures fabric consistency. The air interlacing nozzle is used to introduce intermittent nips to a filament yarn so as to improve its performance in textile processing. This study investigates the effect of interlacing nozzle geometry on the interlacing process. The geometries of interlacing nozzles with multiple air inlets located across the width of a yarn channels are investigated. The basic interlacing nozzle is the yarn channel, with a perpendicular single air inlet in the middle. The yarn channel shapes are cross sections with semicircular or rectangular shapes. This paper presents three doubled sub air inlets with main air inlet and one of them is slightly inclined doubled sub air inlets with main air inlet. The compressed air coming out from the inlet hits the opposing wall of the yarn channel, divides into two branches, flows trough the top side of yarn channel, joins with the compressed air coming out from the sub air inlet and then creates two free jets at both ends of the yarn channel. The compressed air moves in the shape of two opposing directional vortices. The CFD-FASTRAN was used to perform steady simulations of impinging jet flow inside of the interlace nozzles. The vortical structure and the flow pattern such as pressure contour, particle traces, velocity vector plots inside of interlace nozzle geometry are discussed in this paper.

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Design of Advanced PCM Encoder Architecture for Efficient Channel Information Memory Management (효율적인 채널 정보 메모리 관리를 위한 PCM 엔코더 설계)

  • Ro, Yun-Hee;Kim, Geon-Hee;Kim, Dong-Young;Kim, Bok-Ki;Lee, Nam-Sik
    • Journal of Advanced Navigation Technology
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    • v.24 no.4
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    • pp.305-313
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    • 2020
  • Telemetry system is a system that transmits status information data acquired from the aircraft to the ground station. PCM encoder needs memory to store channel information in order to generate a frame format using the acquired data. Generally, telemetry systems in large aircraft require much larger memory for the increased acquisition channel information due to the increased sensors and subsystems. However, they have difficulty to store all channel information in limited memory. In this paper, we suggests and implements an advanced PCM encoder that can efficiently manage memory by minimizing duplicated channel information. This novel PCM encoder allocates duplicated channel information to memory only once. And, sub commutation channels having different information for each minor frame are allocated to the memory by multiples of sub commutation channels. Finally, the suggested PCM encoder was proved by simulation that composed channels of various measurement cycles.

Effect of ECAP on Microstructure of SiCw/6061Al Composites Produced by Powder Metallurgy (분말야금공정으로 제조한 SiCw/6061Al 복합재료의 미세조직에 미치는 ECAP가공의 영향)

  • Chang, Si-Young
    • Journal of Powder Materials
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    • v.9 no.1
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    • pp.11-18
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    • 2002
  • The 6061 Al alloy based composites reinforced with 10 vol% SiC whiskers were prepared by powder metallurgy with the powders having the different sizes, i.e. < $30{\mu}m$ and > $30{\mu}m$ The composites were subjected to equal channel angular pressing (ECAP) at various conditions and the microstructural changes during ECAP were examined In the composites SiC whiskers were clustered and randomly aligned. The clusters were relatively well distributed in the composite with the smaller initial powder size. After ECAP, the clusters were aligned parallel to flow direction and became smaller. In addition, the shape of clusters was changed from irregular to round. The microstructure of the ECAPed samples were compared with those of the conventionally hot-extruded composites. The uniform microstructure and enhanced microhardness could be obtained by using the powders having the smaller size, decreasing ECAP temperature and repeating ECAP.

Mechanism of Relaxation of Rat Aorta by Scopoletin; an Active Constituent of Artemisia Capillaris

  • Kwon Eui Kwang;Jin Sang Sik;oChoi Min H;Hwang Kyung Taek;Shim Jin Chan;Hwang Il Taek;Han Jong Hyun
    • Journal of Physiology & Pathology in Korean Medicine
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    • v.16 no.2
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    • pp.389-396
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    • 2002
  • In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.

Design Consideration of Bulk FinFETs with Locally-Separated-Channel Structures for Sub-50 nm DRAM Cell Transistors

  • Jung, Han-A-Reum;Park, Ki-Heung;Lee, Jong-Ho
    • JSTS:Journal of Semiconductor Technology and Science
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    • v.8 no.2
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    • pp.156-163
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    • 2008
  • We proposed a new $p^+/n^+$ gate locally-separated-channel (LSC) bulk FinFET which has vertically formed oxide region in the center of fin body, and device characteristics were optimized and compared with that of normal channel (NC) FinFET. Key device characteristics were investigated by changing length of $n^+$ poly-Si gate ($L_s$), the material filling the trench, and the width and length of the trench at a given gate length ($L_g$). Using 3-dimensional simulations, we confirmed that short-channel effects were properly suppressed although the fin width was the same as that of NC device. The LSC device having the trench non-overlapped with the source/drain diffusion region showed excellent $I_{off}$ suitable for sub-50 nm DRAM cell transistors. Design of the LSC devices were performed to get reasonable $L_s/L_g$ and channel fin width ($W_{cfin}$) at given $L_gs$ of 30 nm, 40 nm, and 50 nm.

Paper-based Electrochemical Sensor Using a Self-operated Paper Pump (자발 구동형 종이 펌프를 이용한 종이 전기화학 센서)

  • Si Hiep Hua;Chikwan Kim;Duc Cuong Nguyen;Yong Shin Kim
    • Journal of Sensor Science and Technology
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    • v.33 no.3
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    • pp.158-164
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    • 2024
  • We developed a self-operated paper pump that can maintain a nearly constant flow rate of an aqueous solution along a paper strip channel in paper-based analytical devices (PADs). The quasi-stationary flow rate was controlled by increasing the crosssectional channel area (capillary force) using a fan-shaped absorption pad coupled with a paper strip channel. The flow rate is regulated by varying the fan angle of the circular absorbing pad. Furthermore, the flow rate can be increased by furnishing a hollow cavity at the center of a conventional paper strip channel. The rate was regulated by varying the length of the hollow paper channel in the flow rate range of 5.1-26.4 mm/min. As a preliminary work, a paper-pump-coupled PAD was fabricated, and its CV detection capability was evaluated for the redox reaction of Fe(CN)6+4/+3. The combination of a paper pump with a PAD resulted in an ideal CV curve with a higher limiting current and faster response time. These results are interpreted well by the Levich equation, which suggests that the paper pump is a very useful component in paper-based sensors.

Performance Analysis of MC DS-CDMA System using Turbo Code in Multipath Rayleigh Fading Channel (다중경로 레일리 페이딩 채널에서 Turbo 부호를 적용한 MC DS-CDMA 시스템의 성능 분석)

  • 박기식
    • Journal of the Korea Institute of Information and Communication Engineering
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    • v.5 no.5
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    • pp.902-907
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    • 2001
  • In this paper, we analyzed BER performance of the MC DS-CDMA system and evaluated the degree of performance improvement of the system caused by adopting turbo code recently receiving much attention due to its powerful coding capability. As a result of analysis, it was found that the MC DS-CDMA system without any powerful coding scheme can not serve voice quality $(BER : 10^{-3}$ regardless of the number of users and the value of $(BER : 10^{-3)$ in Rayleigh fading channel. On the other hand, it was found that the MC DS-CDMA system adopting turbo code for performance improvement, shows improved BER performance and can serve voice quality without regard to the number of users and the value of $(BER : 10^{-3)$ in the same channel. For example, when $(BER : 10^{-3)$ is l0dB and the number of users was 10, the MC DS-CDMA system adopting turbo code showed improved BER performance about $5\times10^{-3}$.

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Open channel block of Kv1.4 potassium channels by aripiprazole

  • Park, Jeaneun;Cho, Kwang-Hyun;Lee, Hong Joon;Choi, Jin-Sung;Rhie, Duck-Joo
    • The Korean Journal of Physiology and Pharmacology
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    • v.24 no.6
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    • pp.545-553
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    • 2020
  • Aripiprazole is a quinolinone derivative approved as an atypical antipsychotic drug for the treatment of schizophrenia and bipolar disorder. It acts as with partial agonist activities at the dopamine D2 receptors. Although it is known to be relatively safe for patients with cardiac ailments, less is known about the effect of aripiprazole on voltage-gated ion channels such as transient A-type K+ channels, which are important for the repolarization of cardiac and neuronal action potentials. Here, we investigated the effects of aripiprazole on Kv1.4 currents expressed in HEK293 cells using a whole-cell patch-clamp technique. Aripiprazole blocked Kv1.4 channels in a concentration-dependent manner with an IC50 value of 4.4 μM and a Hill coefficient of 2.5. Aripiprazole also accelerated the activation (time-to-peak) and inactivation kinetics. Aripiprazole induced a voltage-dependent (δ = 0.17) inhibition, which was use-dependent with successive pulses on Kv1.4 currents without altering the time course of recovery from inactivation. Dehydroaripiprazole, an active metabolite of aripiprazole, inhibited Kv1.4 with an IC50 value of 6.3 μM (p < 0.05 compared with aripiprazole) with a Hill coefficient of 2.0. Furthermore, aripiprazole inhibited Kv4.3 currents to a similar extent in a concentration-dependent manner with an IC50 value of 4.9 μM and a Hill coefficient of 2.3. Thus, our results indicate that aripiprazole blocked Kv1.4 by preferentially binding to the open state of the channels.

Optical power splitters and optical intensity modulators utilizing Strain-Optic Waveguides of LiNbO3 (LiNbO3의 스트레인광학형 광도파로를 이용한 세기 광 변조기와 광 파워 분배기)

  • 정홍식
    • Korean Journal of Optics and Photonics
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    • v.14 no.1
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    • pp.38-43
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    • 2003
  • Fabrication process of strain-induced channel waveguides in $LiNbO_3$ was developed using strain-optic effect and compressional strain due to ~1.4 $\mu\textrm{m}$ surface Mo/Pt metal film. Characterization of the channel waveguides revealed a single transverse and depth mode in both TE and TM polarizations. Measurements showed total insertion loss of 6.2 and 7.7 ㏈/cm for TM and TE polarizations. respectively. Electro-optic intensity modulators with 11 mm long electrode length and 21 $\mu\textrm{m}$ electrode gap at $\lambda$ = 1.15 ${\mu}{\textrm}{m}$have been produced in $LiNbO_3$ substrates using strain-induced channel waveguides. Modulation depth of 100% at $\pi$-radian voltage of 16.1V has been demonstrated. Also, 1$\times$2 on/off power splitters at $\lambda$ = 0.63 $\mu\textrm{m}$ have been produced using strain-induced channel waveguides. On/off voltage of $\pm$ 25V has been demonstrated.