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      • 원자층 증착법을 이용한 그래핀 상에서의 high-k 증착 연구

        구예현 성균관대학교 일반대학원 2015 국내석사

        RANK : 247807

        우수한 열적, 물리적 특성과 high mobility의 장점을 가진 그래핀을 채널층으로 사용하는 field effect transistor 구현을 위해서는 atomic layer deposition (ALD)을 사용하여 그래핀 상에 균일한 고유전 게이트 유전체 (high-k gate dielectric)를 증착하는 것이 필수적이다. 그러나 그래핀은 표면에 ALD precursor와 화학적 결합 및 반응을 할 수 있는 dangling bond나 hydroxyl group 등이 존재하지 않아 균일한 박막의 증착이 매우 어려운 단점을 가지고 있다. 따라서 본 연구에서는 다양한 표면 개질법을 사용하여 그래핀 표면을 처리한 후, ALD high-k 증착 특성을 평가하여 최적의 표면 개질법을 찾고자 시도하였다. 우선 아무 처리 하지 않고 ALD를 이용해 그래핀 위에 일정한 두께의 HfO2와 Al2O3를 온도별로 증착하여 성장 mechanism을 비교하였다. 그래핀 표면과 화학적 결합을 하지 못한 precursor가 온도가 높아질수록 열에너지에 의해 desorption되는 경향이 두드러지면서 온도가 높아질수록 high-k 박막의 surface coverage가 떨어지는 경향을 보였다. 이러한 단점을 개선하고자 O3 표면 처리, two-step 증착, NMP (1-​Methyl-​2-​pyrrolidinone) 세정, 다양한 증착법을 통한 inorganic seed layer (sputtered ZnO, e-beam evaporated Hf) 도입 등의 다양한 그래핀의 표면 개질법들을 적용한 후 ALD-HfO2 박막을 증착한 결과, 그래핀의 물리적 damage 없이 HfO2 박막의 균일한 성장을 가장 효과적으로 도운 표면처리 방법은 e-beam evaporation 방법을 사용하여 ∼3 nm 두께의 Hf metal seed를 형성한 경우였다. E-beam evaporation을 통해 그래핀 위에 Hf이 균일하게 물리적으로 증착 될 경우, ex situ 공정과 ALD 공정에 의해 Hf-oxide로 변환되고 효과적인 seed 역할을 하여 그래핀 위 ALD-HfO2의 균일한 성장을 도운 것으로 판단된다.

      • High-throughput sequencing-based identification of airborne Aspergillus species and their triazole susceptibilities

        이승은 서울대학교 보건대학원 2015 국내박사

        RANK : 247807

        Aspergillus is a common fungus presenting everywhere in our environments. The genus Aspergillus currently includes 339 diverse species in 19 sections of Aspergillus, of which about 50 species are known as allergenic and/or pathogenic for human. The pathogenicity of this fungus mostly depends on species-specific characteristics. For instance, two most prevalent pathogenic Aspergillus species, A. fumigatus and A. terreus, produce the smallest conidia that can reach the terminal alveoli to cause pulmonary infection whereas the other pathogenic species producing larger conidia choose the larger routes of infection in our bodies, such as mouth and nose. Plus, the concentrations of airborne Aspergillus species have varied by season and by location. Therefore, from an environmental health point of view, to appropriately understand the properties and the compositions of airborne Aspergillus species is important in our environment with various conditions. Though, the difficulty in to differentiating the closely related species of Aspergillus from environmental specimens presents when high-throughput sequencing-based method is adapted to sensitively detect unculturable and low abundant fungal species together due to an insufficient variability of targeted marker and a potential inaccuracy of reference sequence databases used. In addition, to diagnose the antifungal susceptibility levels of airborne pathogenic Aspergillus species has been difficult owing to a current inconvenience of isolating tremendous amounts of environmental fungal colonies collected by culture plate-based air samplings. To this end, the goal of this study is to facilitate to identify and to measure the concentrations of airborne Aspergillus species and their levels of triazole susceptibilities. Thus the specific aims include to monitor the most powerful antifungal agent, triazole, susceptibilities in airborne Aspergillus species with triazole-containing selective sampling medium (Chapter II), to characterize the accuracy of high-throughput sequencing-based method to identify the species of Aspergillus when adopting alternative markers analysis and curated databases (Chapter III), and to apply this method to identify and to estimate the abundances of airborne Aspergillus species in our environment (Chapter IV). In Chapter II, I estimated the concentration of triazole resistant fungi and Aspergillus in outdoor air of Seoul Capital Area. Although emerging triazole resistant fungi are a concern with the increased use of environmental triazoles, little is known about the levels of triazole susceptibility in outdoor airborne fungi and Aspergillus making it difficult to assess the risks of inhalation exposure to airborne, antifungal-resistant pathogenic Aspergillus. To this end, the impactor air sampling with triazole-containing nutrient agar plates was performed to selectively screen for airborne fungal isolates based on their triazole susceptibilities. The study estimated that 0.17% of all the culturable fungi belong to the pathogenic thermotolerant taxa, among which each isolate of Aspergillus niger and Aspergillus tubingensis showed a minimum inhibitory concentration (MIC) of 2 μg/mL or greater for a clinical triazole, itraconazole, with another pathogenic fungal species, Paecilomyces variotii. The results confirmed the presence of airborne pathogenic species of Aspergillus with high MICs for itraconazole in ambient air. Though vigilance was still required to estimate the relative abundance of these and other pathogenic Aspergillus species in the air due to the limitation of detecting non-culturable and low abundant fungal communities with this culture-based method. In Chapter III, I characterized the accuracy of high-throughput amplicon sequencing to identify the species within the genus Aspergillus. Although high-throughput sequencing has been introduced for fungal ecology studies to sensitively detect target organisms from samples with low abundance such as clinical specimens or air filter samples without requiring culture process, the short amplicons typically used for high-throughput sequencing may result in inaccurate taxonomic assignments due to the limited information available for DNA markers. To maximize the advantage of using high-throughput sequencing to identify pathogenic Aspergillus species in environmental specimens with more accuracy, three DNA markers, the internal transcribed spacer 1 (ITS1), β-tubulin (BenA), and calmodulin (CaM), were sequenced in this study from eight reference Aspergillus strains with known identities using 300-bp sequencing on the Illumina MiSeq platform. The identifications with sequences longer than 250 bp were accurate at the section rank, with some ambiguities observed at the species rank mostly due to cross detection of sibling species. Additionally, in silico analysis was performed to predict the identification accuracy for all species in the genus Aspergillus, where 107, 210, and 187 species were predicted to be identifiable down to the species rank based on ITS1, BenA, and CaM, respectively. The genus-rank identification of Aspergillus was successful to classify more than 99% of Aspergillus species as the genus Aspergillus in silico. Except A. terreus having significant intra-specific variability, the identifiable Aspergillus species defined in silico had more than 96.1, 97.9 and 99.9% genus-rank accuracy; 95.4, 98.3 and 99.5% section-rank accuracy; 95.4, 97.7 and 99.4% species-rank accuracy in vitro with ITS1, BenA and CaM sequinning, individually. The results were reproducible across biological duplicates both at the species- and section-rank, but not strongly correlated between ITS1 and BenA, in air filter samples, suggesting the Aspergillus detection can be taxonomically biased depending on the selection of the DNA markers and/or primers. In Chapter IV, I used the high-throughput sequencing-based method to study seasonal abundances and compositions of airborne Aspergillus species in the Seoul Capital Area. The detections of Aspergillus species from air filter samples were found to be biased dependent on the selection of the DNA markers. For instance, some sections, such as Raperi, Versicolores, Restricti, Aspergillus, Circumdati, and Ochraceorosei were preferentially detected by ITS1 (ITS1/BenA >1); other sections, such as Fumigati, Falvi, Nidulantes, Candidi, Cremei, Sparsi, Cervini, Terrei, Clavati and Aenei were preferentially detected by BenA (ITS1/BenA <1) in 18 air filter samples. By combining ITS1 and BenA, however, a total of 16 pathogenic Aspergillus species were detected while 9 and 8 species were detected only by ITS1 and BenA, respectively, highlighting the complementarity of the two markers in detecting pathogenic Aspergillus species from ambient air. The study found A. fumigatus as the most abundant pathogenic species with 89.6% and 98.3% of relative abundances based on ITS1 and BenA, respectively. Additionally, the taxon-specific concentrations were determined by multiplying relative abundances of Aspergillus species based on the high-throughput sequencing and total fungal concentrations measured by quantitative PCR. The concentration of total pathogenic Aspergillus species was highest in June at the campus but in October at the farm. The concentrations were about 4 times higher at the farm (85 GCN m-3) than at the campus (21 GCN m-3) on average. The concentrations estimated in gene copy numbers (GCN m-3) are not comparable to the doses calculated in culture-based method (CFU m-3). However, as the measurement of the method combining the high-throughput sequencing-based method established in this study and qPCR was reproducible with the defined markers and primers with higher identification accuracy for the species of Aspergillus, the method further can be utilized to conveniently and accurately understand the communities of Aspergillus in a large environmental sample set collected in different locations and in different seasons. In conclusion, this study characterized seasonal compositions and concentrations of airborne pathogenic Aspergillus species and their triazole susceptibilities. The study detected the airborne pathogenic Aspergillus strains with high MICs of a medical triazole of itraconazole from outdoor air of the Seoul Capital Area in South Korea, implying risks of inhalation exposures to triazole-resistant fungal pathogens in general environments. Owing to the abundances of airborne Aspergillus species with high MICs of itraconazole being detected from ambient air, the study further explored the possibility of using the high-throughput sequencing to identify pathogenic species within the genus Aspergillus. In vitro and in silico analyses showed that the high-throughput sequencing was useful to identify Aspergillus species with the ITS1, BenA, and CaM sequences longer than 250 bp. By combining this high-throughput sequencing-based method established in this study that is reproducible with the defined markers/ primers with higher accuracy for the species identification of Aspergillus, and the conventional PCR-based quantification method, more pathogenic Aspergillus species were detectable and quantified with higher accuracy in air filter samples. As the airborne Aspergillus species concentrations estimated by location and season have had different patterns, the method established in this study is thought to be useful to conveniently and accurately understand the communities of Aspergillus in a large environmental sample set collected in different locations and in different seasons.

      • Interfacial reaction between Cu substrate and Zn-5wt.%Al-xwt.%Mg (x=0.5, 1, 2, 3) high temperature solder

        백승문 성균관대학교 일반대학원 2017 국내석사

        RANK : 247807

        With the recent ultra-light weighted and highly-densed electronic parts, the step soldering process, in which soldering is done repeatedly going through several stages from high temperature to low temperature is increasing and the use of electronic parts in high temperature environment is also increasing. There have been much research reported on solder so far, but there are few studies on substrate and high-temperature solder that can be applied in high temperature environment. Currently, Pb-containing high temperature solder continues to be used, but Pb-containing high temperature solder has a problem from human health risk and environmental conservation aspects and thus it is now a desperate situation that needs to conduct a study on eco-friendly and economic high temperature solder to replace this. To replace the Pb-containing high temperature solder, various alloys such as Sn-Sb, Bi-Ag, Zn-Al, and Zn-Sn have been proposed, but this study selected Zn-Al-based solder with an excellent thermal and mechanical property and to improve internal resistance as well as mechanical and electrical properties, added Mg and found the correlation between microstructure and mechanical property depending on content of Mg ( X = 0.5, 1, 2, 3 ) in Zn-5wt.%Al-Xwt.%Mg alloy solder, and developed a new high temperature solder. Zn-5wt.%Al-Xwt.%Mg alloy solder depending on content of Mg was manufactured with parental alloy in an induction furnace at a relatively lower temperature than the general solder manufacturing process without using a high degree vacuum, mixed phase was formed on interfacial reaction layer at Zn-5wt.%Al-3wt.%Mg alloy through heat treatment at 420℃, and for analysing the formed mixed phase, additional experiment was conducted by differing the heat treatment time. Also, to evaluate the correlation between microstructure and mechanical property depending on composition of Mg, Scanning Electron Microscope (SEM) and Transmission Electron Microscope (TEM) were used for microstructure and chemical composition analysis, and the tendency of mechanical property between Zn-5wt.%Al-xwt.%Mg alloy solder and Cu substrate was analyzed through shear test. As a result, it was found that within the range of composition of Mg (0.5wt.%~2wt.%), as the content of Mg increased, the mechanical property after heat treatment increased. But in composition of Zn-5wt.%Al-3wt.%Mg, the mechanical property became worse. This could be because of mixed phase generated at composition of Zn-5wt.%Al-3wt.%Mg.

      • Accurate and Efficient High-Order Spatial Scheme for Rotorcraft Flow Analysis

        홍윤표 서울대학교 대학원 2023 국내박사

        RANK : 247807

        As a growing number of next-generation rotorcraft are being newly developed for urban air mobility these days, demands for accurate aerodynamic and aeroacoustic performance analysis of the new configurations are increasing. Higher-fidelity analyses require advanced numerical techniques, among which high-order accurate spatial discretization schemes are the most critical. Several concepts of spatial schemes previously presented have been applied for a relatively simple type of helicopter performance analysis and have produced satisfactory results when a large number of grids are involved. However, since the newly developed rotorcraft commonly adopt multiple propulsors which require a grid level several times higher than the grid level used for single helicopter analysis, the accuracy of the spatial discretization method must be enhanced. In addition, it is necessary to determine which numerical characteristics are essential to the accurate analysis of the rotorcraft flow field. The doctoral research was initiated in light of the aforementioned background, and the core results are as follows. First, an improved high-order accurate spatial discretization scheme, eMLP-VC, was developed based on the characteristics of the rotorcraft flow field, such as vortex-dominated, subsonic to supersonic flow speed, and highly unsteady. The accuracy, robustness, and efficiency were improved compared to the baseline scheme, eMLP. Through one- and two-dimensional benchmark tests, eMLP-VC was demonstrated to be superior, specifically in vortex-dominated and compressible flow fields. Moreover, eMLP-VC can maintain its robustness in the hypersonic flow dominated by strong shock waves. Second, a local-order-of-accuracy index (LAI) was suggested which allows quantitative comparison between the developed eMLP-VC and conventional high-order accurate spatial discretization schemes. High-order accurate spatial discretization schemes used in compressible flows usually produce reduced accuracies locally in the continuous flow because of the shock-sensing algorithm. As the local reduction in accuracy in the discretized domain reduces the fidelity of the flow solver, it is necessary to quantify the amount of accuracy reduction and investigate the numerical techniques that minimize the decrease in accuracy. The LAI newly suggested in this thesis can show the region where the order-of-accuracy decreases, and it can be applied to any type of spatial discretization method that uses explicit reconstruction. Several high-order accurate spatial discretization schemes, including the one presented in this thesis, were compared through the LAI analyses in the one- and two-dimensional benchmark tests. Two numerical characteristics essential for high-fidelity rotorcraft aerodynamic analysis could be identified: advanced shock-sensing algorithm and hybrid central-upwind characteristics. Third, eMLP-VC was applied to actual three-dimensional complicated flow field analysis of rotorcraft. Even with a coarse grid system, the unsteady vortex dynamics of PROWIM model and the HART-II rotor can be captured. In particular, the aeroacoustic noise generated by blade-vortex interaction in HART-II rotor could be predicted with high accuracy. Design exploration and optimization of co-rotating coaxial rotor, applicable to the urban air mobility aircraft, were also conducted using the high-fidelity solver with eMLP-VC. It has been demonstrated that eMLP-VC can be sufficiently useful for the development of a new type of next-generation rotorcraft. 도심항공교통을 위한 새로운 컨셉의 수직 이착륙기에 대한 연구가 증가하며, 새로운 형상에 대한 정확한 공력 및 공력 소음 성능 해석에 대한 수요가 증가하고 있다. 기존에 제시되었던 여러 컨셉의 고차 정확도 공간 차분법은 비교적 간단한 형태의 헬리콥터 성능 해석에 활용된 바 있으며, 많은 수의 격자가 동반될 때 만족할 만한 수준의 결과를 낸 바 있다. 그러나 다중 로터를 공통적으로 사용하는 새로운 컨셉의 수직 이착륙기는 기존에 헬리콥터 해석에 사용되던 격자 수준의 몇 배를 필요로 하기 때문에, 공간 차분법의 해석 정확도를 더욱 높게 개발할 필요가 있다. 본 연구에서는 기존의 고차 정확도 스킴인 eMLP를 수직 이착륙기 유동장 특징에 맞춰 개선하였다. 비정상적인 와류가 지배적이며, 아음속부터 초음속까지 전 마하수를 아우르는 유속의 존재 등을 고려하여 정확도와 강건성, 그리고 효율성을 개선한 eMLP-VC를 제시하였다. 일, 이차원의 벤치마크 테스트를 통해 새롭게 제시된 eMLP-VC의 우수성을 보였으며, 특히 로터 유동장 뿐만 아니라 극초음속의 충각파가 지배적인 유동에서도 강건함을 유지하는 것을 보였다. 개발된 eMLP-VC와 타 고차 정확도 스킴의 정량적인 비교를 위해 새로운 국부 공간 정확도 지수인 local-order-of-accuracy index (LAI)를 제시하였다. 압축성 유동에서 사용되는 고차 정확도 스킴들이 아음속의 연속성을 갖는 유동에서 정확도가 감소되기 때문에, 스킴의 정확도 차이가 생긴다. 차분된 공간에서 국부적으로 감소되는 정확도가 결과적으로 유동 해석 충실도를 감소시키기 때문에, 이를 분석하여 정확도 감소를 최소화할 필요가 있다. 본 연구에서 새롭게 제시된 LAI은 외재적으로 보간하는 모든 공간 차분 방법에 대해 적용할 수 있으며, 이를 통해 유동장의 어떤 부분에서 정확도 감소가 일어나는 지 확인할 수 있다. 일, 이차원 벤치마크 테스트를 통해, 본 연구에서 제시한 스킴을 포함한 여러 고차 정확도 스킴들을 비교하였고, 결과적으로 수직 이착륙기 고정확도 해석에 있어 반드시 필요한 수치적 특성을 밝혀낼 수 있었다. 우선, 적은 격자 수준에서 와류가 충격파와 비슷한 수치적 특성을 보이기 때문에, 이를 충격파로 잘못 인지하여 수치 소산을 가하지 않아야 한다. 즉, 이를 위해 충격파 센싱 기법이 고도화되어야 할 필요가 있다. 두번째로, 아음속 영역에서 중앙 차분을 이용함으로써 풍상 차분법의 낮은 정확도를 보완할 필요가 있다. 초음속 영역에서는 강건한 풍상 차분법을 유지하고, 아음속 영역에서는 정확도가 높은 중앙 차분을 혼합하여 이용함으로써, 해석자의 정확도와 강건성을 모두 보장할 수 있다. 마지막으로 세 가지 수직 이착륙기 유동장에 eMLP-VC를 이용하여 해석을 진행하고, 최적 설계를 고정밀도 해석자를 이용하여 진행함으로써, 새로운 형상의 수직 이착륙기 개발에 본 연구에서 제시된 스킴이 충분히 활용될 수 있음을 보였다. PROWIM 모델과 HART-II 로터에서 적은 격자를 가지고도 충분히 와류를 보존하고 와류의 비정상적인 거동을 포착할 수 있음을 보였다. 특히, HART-II 로터에서 발생하는 공력 소음까지도 정확한 수준으로 예측할 수 있음을 보였다. 실제 도심항공교통 수직 이착륙기에 적용 가능한 적층 로터 형상 최적 설계에도 활용하였다. 최적 설계된 형상에 대해 초정밀 해석을 진행하고, 이를 통해 최적 설계가 제대로 이루어졌음을 확인하였다. 결과적으로 개발된 스킴, eMLP-VC가 성공적으로 수직 이착륙기 개발에 사용될 수 있음을 확인하였다.

      • Effect of Hemin on High-fat Diet-induced Insulin Resistance

        주태진 영남대학교 대학원 2013 국내석사

        RANK : 247807

        Heme oxigenase-1 (HO-1) is a stress-responsive protein induced by various oxidative agents, and plays a important role against the oxidative process. Hemin is known to alleviate oxidative stress by inducing HO-1. In the present study, we examined the effect of hemin on high-fat diet induced insulin resistance in C57BL/6 mice using hyperinsulinemic-euglycemic clamp. Mice were divided into Chow diet (CD), CD+Hemin (CDH), High-fat diet (HFD) and HFD+hemin (HFDH). High-fat diet was fed for 4 weeks and hemin solved in dimethylsulfoxide (DMSO) was injected intraperitoneally (50 μmol/kg) every day during high-fat feeding. High-fat diet increased food intake in both HFD and HFDH compared with CD and there was no different between HFD and HFDH. High-fat diet increased body weight and fat mass in HFD compared with CD. However, body weight and fat mass in HFDH were not increased by high-fat diet. High-fat diet significantly increased the plasma levels of free fatty acids (FFA) and triglyceride in HFD compared with CD. HFDH significantly decreased the plasma levels of FFA and triglyceride compared with HFD. High-fat diet decreased glucose infusion rate (GIR) and whole body glucose uptake in HFD, whereas it did not decrease GIR and whole body glucose uptake in HFDH compared with CD. Basal hepatic glucose production was similar among the groups. High-fat diet significantly increased clmap hepatic glucose production in HFD and HFDH and there was no difference between the two groups. High-fat diet decreased skeletal muscle glucose uptake in HFD compared with CD. However, skeletal muscle glucose uptake in HFDH was not decreased compared with CD and it was significantly higher compared with HFD. High-fat diet significantly increased skeletal muscle triglyceride in HFD compared with CD. HFDH significantly decreased skeletal muscle triglyceride compared with HFD. HO-1 protein level was increased in skeletal muscle of CDH, HFD and HFDH compared with CD. HO-1 level in HFDH was significantly higher than that of HFD. High-fat diet decreased phosphorylated AMP-activated protein kinase (pAMPK) protein level in skeletal muscle of HFD compared with CD. HFDH significantly increased pAMPK protein level compared with HFD. High-fat diet significantly increased gene expression of sterol regulatory element-binding protein 1 (SREBP1), fatty acid synthase (FAS) and acetyl CoA carboxylase (ACC) in skeletal muscle of HFD and HFDH compared with CD. HFDH significantly decreased gene expression of SREBP1, FAS and ACC compared with HFD. High-fat diet increased gene expression of cluster of differentiation 36 (CD36) and scavenger receptor A1 (SRA1) in skeletal muscle of HFD compared with CD. HFDH decreased gene expression of SRA1 compared with HFD. High-fat diet decreased gene expression of peroxisome proliferator-activated receptor α (PPARα) and acetyl CoA oxidase (ACO) in skeletal muscle of HFD compared with CD. HFDH increased gene expression of PPARα and ACO compared with HFD. High-fat diet increased gene expression of tumor necorosis factor-α (TNF-α), interlukine-6 (IL-6), interlukine-1β (IL-1β) and inducible nitric oxide synthase (iNOS) in skeletal muscle of HFD compared with CD. HFDH decreased gene expression of TNF-α, IL-6, IL-1β and iNOS compared with HFD. High-fat diet decreased gene expression of superoxide dismutase (SOD) and glutathione peroxidase1 (GPX1) in skeletal muscle of HFD compared with CD. HFDH increased gene expression of SOD and GPX1 compared with HFD. High-fat diet significantly increased nitrotyrosine protein level in skeletal muscle of HFD compared with CD. Hemin treatment significantly decreased nitrotyrosine protein level compared with HFD. High-fat diet significantly increased the level of triglyceride in liver of HFD and HFDH compared with CD, and there was no difference between the two groups. HFDH significantly increased HO-1 protein level compared with CD. Phosphorylated AMPK protein levels were similar among the groups in liver. High-fat diet significantly increased gene expression of SREBP1, FAS and ACC in liver. HFDH had no effect on gene expression of SREBP1, FAS and ACC. High-fat diet increased gene expression of CD36 and SRA1 in liver of HFD and HFDH compared with CD. HFDH did not decrease gene expression of CD36 and SRA1 compared with HFD. High-fat diet decreased gene expression of PPARα and ACO in liver of HFD and HFDH compared with CD. HFDH did not increase gene expression of PPARα and ACO compared with HFD. High-fat diet increased gene expression of TNF-α, IL-6, IL-1β and iNOS in liver of HFD and HFDH compared with CD. Hemin treatment did not decrease gene expression of TNF-α, IL-6, IL-1β and iNOS compared with HFD. High-fat diet decreased gene expression of SOD and GPX1 in liver of HFD and HFDH compared with CD. Hemin treatment did not increase gene expression of SOD and GPX1 compared with HFD. These results suggest that hemin has a protective effect on high-fat diet induced insulin resistance by suppression of inflammation, oxidative stress and fat accumulation in skeletal muscle of high-fat fed mice. However, Hemin did not improve insulin resistance in liver of high-fat fed mice.

      • Insights into High-Pathogenicity Avian Influenza in South Korea : Evolution, Epidemiology, and Pathobiology

        이선학 건국대학교 대학원 2024 국내박사

        RANK : 247807

        고병원성 조류 인플루엔자(High Pathogenicity Avian Influenza: HPAI)는 가금류 산업과 공중 보건 모두에 치명적인 영향을 미쳤다. 1996년 중국 광동에서 거위로부터 고병원성 조류 인플루엔자 바이러스 (High Patho-genicity Avian Influenza Virus: HPAI HPAIV) A(H5N1)가 처음 발견된 이후, 그 후손은 헤마글루티닌(HA) 유전자 특이적 계통군(clade 0-7)과 하위 계통군으로 진화하여 대륙간 감염을 유발했다. 수십 년에 걸쳐 H5 HPAIV는 저병원성 조류 인플루엔자 바이러스(Low Pathogenicity Avian Influenza Virus: LPAIV)와의 재조합에 의해 생성된 여러 하위 아형(subtype) 및 유전자형(genotype)으로 진화했으며, 이로 인해 2013~2014년 중국 동부에서 clade 2.3.4.4 H5Nx HPAIV가 출현했다. 2016년 중반, 유라시아 LPAIV의 내부 유전자를 포함하는 재조합 H5N8 계통군 2.3.4.4b HPAIV가 러시아의 Uvs-Nuur 호수와 중국의 Qinghai 호수의 야생 조류에서 발견되었다. 이 바이러스는 2016~2017년에 유럽에서 대규모 발병을 일으켰다. 그 후, 다양한 신규 재배열 H5N8 HPAIV 균주가 유라시아에서 검출되었다. 2020년 후반에 새로운 재조합 clade 2.3.4.4b H5N1 HPAIV가 검출되어 유럽의 가금류와 야생 조류에서 우세해졌다. 최근 2.3.4.4 H5Nx 바이러스의 광범위한 진화는 야생조류 감염과 장거리 이주가 기여하였으며, 바이러스의 유전적 다양화와 광범위한 전파를 가능하게 했다. 국내 가금류 산업은 2000년대 초반부터 새로운 HPAI 균주의 유입으로 해마다 어려움을 겪어왔다. 대부분의 HPAI 발생의 경우, 다른 국가에서 야생 물새의 이주가 국내 가금류 농장에 새로운 HPAI 도입의 주요 원인으로 의심되어 왔다. 본 연구에서는 한국의 야생 조류에서 분리된 clade 2.3.4.4b HPAIV의 유전적 특성을 염기서열 분석을 통해 조사했다. 그 후 병원성과 전파력을 세 종의 야생조류와 국내 가금류에서 검사했으며, 특히 대한민국 가금류에서 엔데믹화 된 H9N2 LPAIV에 대한 전국적인 백신을 고려하였다. 이 연구의 목적은 대한민국에서 HPAIV의 역학과 병원성을 이해하는 것이다. 이 지식은 효과적인 질병 통제 및 가금류의 질병 발병을 최소화하기 위한 과학적 기초를 개발하는 데 중요하다. 1장에서는 한국의 야생조류와 가금류 모두에서 보고된 HPAIV에 대한 연구를 종합적으로 요약한다. 한국에서는 모두 Gs/GD 계열 바이러스의 후손인 다양한 재배열체를 운반하는 세 가지 다양한 H5Nx 하위 유형(H5N1, H5N6, H5N8)이 반복적으로 침입하는 것을 확인했다. 2003년 국내에 도입된 이후 뚜렷한 재조합을 갖는 주요 H5Nx 아형(H5N1, H5N6, H5N8)의 반복적인 침입이 발생했다. 2014~2016년에 계통군 2.3.4.4 H5N8 HPAIV로 인한 한국 최대 규모의 조류 인플루엔자 전염병을 포함하여 주목할만한 발병으로 인해 상당한 경제적 손실이 발생했다. 2016~2017년과 2017~2018년에 새로운 재배열체 계통군 2.3.4.4 H5N6 바이러스를 특징으로 하는 후속 발병으로 인해 440개 농장에서 10억 마리의 새가 손실되어 국가 최대의 경제적 손실을 기록했다. 2018년 4월부터 2020년 9월까지 HPAI 바이러스가 없었던 후, 새롭게 등장한 H5N8 계통군 2.3.4.4b 유럽 계통과 밀접하게 관련된 HPAI 바이러스가 야생 조류에서 검출되어 가금류 농장 발병을 촉발했다. 최근 동일한 계통의 H5N1 HPAI 바이러스가 계절적으로 도입되면서 21/22년과 22/23년 겨울에 두 차례의 후속 발병이 발생했다. 2장에서는 역학적 특성을 알아보기 위해 20/21년 겨울철에 분리된 HPAIV의 유전자 분석을 실시하였다. 2020~2021년 동안 H5N8 HPAIV가 한국의 숙주 종 수준에서 어떻게 확산되는지 더 잘 이해하기 위해 Bayesian 계통발생 분석을 사용하여 조상 상태 재구성과 다양한 종의 야생 조류 및 가금류 간의 숙주 전이 역학 추정을 수행했다. 결과는 H5N8 HPAIV가 야생 오리나 야생조류에서 국내 가금류로의 전염될 가능성이 가장 높다는 것을 뒷받침하며, 이는 야생 오리가 한국에서 가금류 및 기타 종의 유지 관리, 유입에 중심적인 역할을 한다는 것을 시사한다. 또한, 야생조류에서 검출된 바이러스와 같은 유전형을 갖는 바이러스를 이용하여 원앙(Aix galericulata), 청둥오리(Anas platyrhynchos), 홍머리오리 (Mareca penelope) 3종의 야생조류에 대한 HPAIV의 병원성을 조사하였다. H5N8 바이러스를 실험적으로 접종한 야생조류들 중 임상 증상이나 폐사는 나타나지 않았다. 인후두와 총배설강에서 배출된 고농도의 바이러스로 인해 원앙 한 마리를 제외한 합사시킨 야생조류에서 감염이 확인됐다. 감염된 야생조류에서 여러 장기에서 바이러스 항원이 검출돼 HPAI 바이러스 감염의 특징인 전신감염을 나타냈다. 이 발견은 세 야생조류 종에 무증상 감염으로 야생조류간 clade 2.3.4.4b H5N8 HPAIV 전파에 영향을 미쳐 장거리 전파를 가능하게 함을 시사한다. 3장에서는 엔데믹한 H9N2 감염과 백신을 재현하는 각기 다른 면역 상태에서 clade 2.3.4.4b H5N1 HPAIV의 병원성을 검사했다. 세 그룹의 닭에 고농도(108.0EID50), 중농도(106.0EID50), 저농도(104.0EID50)의 바이러스를 비강 내 접종한 후 임상증상과 인후두와 총배설강에서 배출된 바이러스 농도를 검사했다. 한 그룹(G1)은 대조군 닭으로 구성되었고, G2 그룹은 Y280-lineage H9N2 LPAIV에 감염시켰으며, G3 그룹은 Y439-lineage H9N2 LPAIV의 백신 접종하였다. 고용량의 바이러스를 비강 내 접종하면 모든 그룹에서 100% 폐사가 나타났지만 G1, G2, G3에서는 평균 사망 시간(MDT)이 각각 2.6일, 4일, 6.7일로 달랐다. 고농도 접종군의 생존 곡선은 그룹 간에 유의미한 차이가 있었지만(p<0.01) 중농도와 저농도의 생존 곡선은 유의미한 차이가 없었다. 자연감염이나 백신에 노출되지 않은 G1에서 공격접종 바이러스의 BLD50은 105.0EID50이었다. 감염된 각 닭의 인후두 및 배설강 경로의 바이러스 역가는 사망 직전에 가장 높았다. 바이러스 역가는 폐사 하루 전에 가장 높았으며, 평균 바이러스 역가는 인후두에서 104.7EID50이었고, 총배설강에서 104.2EID50이었다. 바이러스 역가 평균을 기반으로, G2 및 G3 그룹에서 바이러스 역가가 G1에 비해 더 높았다. 한국의 자연감염 및 백신을 실험적으로 재현한 닭에서 H9N2 LPAI 바이러스의 감염 또는 백신 접종은 2021-22년 유행 HPAIV 접종에 대한 보호를 제공하지 못했지만 생존 기간을 연장하고 질병 발병을 지연시킬 수 있었다. 결론적으로, 이들 연구는 한국에서 발생한 고병원성 조류인플루엔자 바이러스의 포괄적인 발생에 대한 유전적 개요를 제공했으며, 특히 2020~21년 겨울 동안 개별 균주의 유전적 기여를 확인했다. 또한, 바이러스가 확산 및 역학에 미치는 영향을 조사하기 위해 야생 조류와 가금류를 모두 사용한 병리생물학적 분석을 수행했다. 바이러스 생태를 더 잘 이해하기 위해 이러한 바이러스의 확산을 모니터링하려면 HPAIV에 대한 향상된 능동 감시가 필요하다. 주제어: 고병원성 조류인플루엔자, clade 2.3.4.4b, H5N8, H5N1, 가금류, 야생조류, 병원성, 계통수 분석 Insights into High-Pathogenicity Avian Influenza in South Korea: Evolution, Epidemiology, and Pathobiology Sun-Hak Lee Department of Veterinary Medicine Graduate School of Konkuk University High Pathogenicity Avian Influenza (HPAI) strains have had devastating impacts on both poultry industry and public health. Since the first detection of High Pathogenicity Avian Influenza virus (HPAIV) A(H5N1) from a goose in 1996 in Guangdong, China, its descendants have evolved into multiple hemagglutinin (HA) gene-specific clades (clade 0-7) and subclades causing intercontinental epizootics. Over several decades, H5 HPAIVs have diversified into multiple subtypes and genotypes generated by reassortment with low pathogenicity avian influenza viruses (LPAIVs). This led to emergence of clade 2.3.4.4 H5Nx HPAIVs in eastern China during 2013–2014. In mid- 2016, reassortant H5N8 clade 2.3.4.4b HPAIVs that contained internal genes of LPAIVs from Eurasia were detected in wild birds at Uvs-Nuur Lake in Russia and Qinghai Lake in China; the viruses caused large outbreaks in Europe during 2016– 2017. Subsequently, various novel reassortant H5N8 HPAIVs were detected in Eurasia. In late 2020, novel reassortant clade 2.3.4.4b H5N1 HPAIVs were detected and became predominant in Europe in poultry and wild birds. The recent extensive evolution of the 2.3.4.4 H5Nx viruses is attributed to wild birds infection and their long-distance migration, which facilitates widespread dissemination and genetic diversification of the virus. The poultry industry in South Korea has faced significant challenges since the early 2000s due to the introduction of novel HPAI strains. For the most HPAI outbreaks, migration of wild waterfowl from other countries has been suspected as a major source of novel HPAI introduction to domestic poultry farms. In this study, genetic characterization of clade 2.3.4.4b viruses isolated from wild birds in South Korea was conducted by phylogenetic analysis. Then, the pathogenicity and infectivity were tested in three different wild bird species and domestic poultry, specifically considering widespread immunization of Korean poultry against the endemic H9N2 low pathogenic avian influenza. The aim of these studies was to understand the epidemiology and pathogenicity of highly pathogenic avian influenza viruses (HPAIVs) in South Korea. This knowledge is crucial for developing scientific bases for effective disease control and minimizing outbreaks in poultry. In chapter I, a comprehensive summary of research on HPAIVs reported in both wild birds and poultry in South Korea. South Korea has seen recurring incursions of major three varying H5Nx subtypes (H5N1, H5N6, H5N8) carrying multiple distinct reassortants, all descendants of the Gs/GD-lineage viruses. Since its introduction to South Korea in 2003, recurring incursions of major H5Nx subtypes (H5N1, H5N6, H5N8) with distinct reassortants have occurred. Notable outbreaks, including the largest avian influenza epidemic in South Korea caused by clade 2.3.4.4 H5N8 HPAIV during 2014–2016, led to substantial economic losses. Subsequent outbreaks in 2016– 2017 and 2017–2018, featuring novel reassortant clade 2.3.4.4 H5N6 viruses, resulted in the loss of one billion birds in 440 farms, marking the country's largest economic losses. After an absence of HPAI virus from April 2018 to September 2020, newly emerging H5N8 clade 2.3.4.4b HPAI viruses closely related to European strains were detected in wild birds, triggering poultry farm outbreaks. Recent seasonal introductions of H5N1 HPAI viruses with the same clade led to two subsequent outbreaks in the 21/22 and 22/23 winter seasons. In chapter II, genetic analysis of HPAIV isolated in 20/21 winter season was conducted to investigate epidemiological characteristics. To better understand how H5N8 HPAIVs spread at host species level in Korea during 2020-2021, a Bayesian phylogenetic analysis was used for ancestral state reconstruction and estimation of the host transition dynamics among various species of wild birds and poultry. The results support that H5N8 HPAIV most likely transmitted from wild birds and wild ducks to domestic poultry, suggesting other wild birds and wild ducks play a central role in the maintenance, introduction to poultry and other species. Furthermore, for the investigation of the pathogenicity of this HPAIV, an H5N8 HPAIV possessing the same genotype detected in wild birds was tested in three species of wild birds: Mandarin Ducks (Aix galericulata), Mallards (Anas platyrhynchos), and Eurasian Wigeons (Mareca penelope). None of the birds experimentally inoculated with H5N8 viruses showed clinical signs or mortality. High titer of virus shedding via oropharynx and cloaca resulted in contact transmission to co-housed birds except for one mandarin duck. The presence of viral antigens in multiple internal organs of infected birds suggests a systemic infection, a characteristic feature of HPAI infection. These findings suggest that subclinical infections in all three wild bird species affected to the spread of the clade 2.3.4.4b H5N8 HPAI virus among wild birds, subsequently enabling its long- distance transmission. In chapter III, the pathogenicity of the clade 2.3.4.4b H5N1 HPAIV was examined under different immunological states simulating endemic H9N2 infection and vaccination. Clinical signs and viral loads from oropharyngeal and cloacal routes were examined following intranasal inoculation of the high (108.0EID50), medium (106.0EID50), and low (104.0EID50) doses of the virus in three groups of chickens. One group consisted of naïve chickens (G1), another group was infected with the Y280- lineage H9N2 LPAIV (G2), and another group was vaccinated with the Y439-lineage H9N2 LPAIV (G3). Intranasal inoculation with a high dose of the virus resulted in 100% morality in all groups but different mean death time (MDT) in G1, G2, and G3 for 2.6d, 4d, and 6.7d, respectively. The survival curves of high dose were significantly different among groups (p < 0.01) but not those of medium and low doses. The bird lethal does fifty percent (BLD50) of the challenge strain virus in G1 was 105.0EID50 and this index was not affected by pre-infection and vaccination. Viral titers peaked just one day before the death, with the average virus titer measured 104.7EID50 in the oropharyngeal swabs and 104.2EID50 in the cloacal swabs. On average, virus titers were higher in groups G2 and G3 compared to G1. In experimentally simulated chickens grown in South Korea, the prevalence of infection or vaccination of H9N2 LPAI viruses did not provide protection against the HPAIV inoculation but could result in prolonged survival time and delayed the onset of disease. In conclusion, these studies provided a genetic overview of the comprehensive outbreak of highly pathogenic avian influenza viruses in Korea, specifically confirming the genetic contributions of individual strains during the winter of 2020-21. Furthermore, pathobiological analysis using both wild birds and poultry to investigate the impact of the virus on its spread and epidemiology. Enhanced active surveillance for HPAIVs is needed to monitor the spread of these viruses to better understand the viral ecology. Keyword: High pathogenicity avian influenza, clade 2.3.4.4b, H5N8, H5N1, Poultry, Wild birds, pathogenicity, phylogenetic analysis

      • 고해상도 모바일 디스플레이를 위한 인터페이스 및 구동 기법 : Interface and Driving Methodologies for High-Resolution Mobile Displays

        김진호 한양대학교 대학원 2008 국내박사

        RANK : 247807

        High-speed signaling techniques ensuring signal integrity have been one of the key technologies in flat panel displays to handle a variety of multimedia contents and to transfer or process the large amount of data. In addition, the display devices should provide the contents with high-quality images. This work investigates the design techniques of high-speed link and its I/O circuits for high-resolution mobile displays to increase signaling rate, simplicity in configuration, and robustness of such links with low power consumption. This work also proposes an image quality enhancement driving method for high-resolution and high-grayscale displays and shows its performance by quantitative analysis and experimental demonstration. To achieve the system simplicity and low cost of display devices as well as their interface system, a single-pair serial link with clock-embedding scheme is proposed. The proposed interface typically transmits and recovers 800Mbps data through single-pair. If it is used in mobile displays, it can support VGA or WVGA format. Compared with MDDI, the proposed serial link has advantages in number of interconnection lines and power consumption. Simulation results show that, for 800Mbps data transfer, the proposed interface needs just two lines and consumes about 8.5mW including input buffer while MDDI needs six transmission lines and consumes about 9.5mW including input buffer. This work also proposes a new receiver circuit for the proposed single-pair serial link. Even in using display interface standards such as LVDS, DVI, HDMI, mini-LVDS, MDDI, MIPI, etc., customization of individual circuit design is inevitable to meet each specification of the different kinds of interface standards. Therefore, a general purpose receiver circuit is proposed to reduce time and efforts put into designing those interface circuits. The negative feedback loop in the proposed receiver that makes self-reset function possible achieves wide bandwidth and low power consumption, and it reduces data-dependent jitter. An experimental receiver prototype has been fabricated in a 0.18μm CMOS technology. Experimental results show that the proposed receiver circuit has data-dependent jitter less than 15% of bit-time. The power consumption of the proposed receiver at 1.6Gbps data recovery is less than 4mW. Compared with the previous LVDS receiver circuits, the proposed receiver can save more than 40% of power. Another major challenge in display driving technologies is to provide high-quality images with high-resolution and high color depth. This work proposes a new driving method to enhance image quality by diffusing errors among adjacent channels, so that the standard deviation between errors can be reduced. Instead of circuit techniques to compensate for or cancel the offsets in the output buffer circuits, the proposed driving method and circuits can be an attractive alternative for image quality enhancement. Quantitative analysis of the proposed driving method shows that it acts like a spatial low-pass filter. With many output channels shared, we can get better performance in reducing channel-to-channel output non-uniformity errors because high frequency noises are filtered out. But, when designing a display driver LSI, the recommended number of sharing channels is determined to be three considering critical flicker frequency and circuit complexity. The prototype of the proposed driving method has been applied to an AMOLED driver IC in a 0.18μm CMOS technology. In driving an AMOLED panel with the proposed driving method, line shaped noises resulting from channel-to-channel output non-uniformity of current driving IC become almost invisible by the image quality enhancement driving method. 정보 기술이 발달함에 따라 디스플레이 장치는 단순한 출력 장치의 기능을 넘어 다양한 멀티미디어 컨텐츠 정보를 고품질의 영상 정보로 변환하여 사용자에게 전달하는 매개체 역할을 하고 있다. 멀티미디어 컨텐츠 종류의 증가 및 다양화로 인해 표현해야 하는 정보량이 증가하고 이러한 정보를 효율적으로 표현하기 위하여 대면적, 고해상도, 고계조 디스플레이 장치가 요구됨에 따라 디스플레이 시스템 내부에서 처리해야 하는 정보량 또한 증가하고 있다. 따라서 디스플레이 시스템 내에서 신호의 무결성을 보장하면서 고속으로 신호를 전송하는 고속 인터페이스 기술이 평판 디스플레이 구동회로 분야에 있어 매우 중요한 기술 중 하나가 되었다. 디스플레이 장치는 안정적이면서도 고속으로 영상 신호를 전달하고 처리하는 것뿐만 아니라, 이렇게 전달 받은 영상 신호를 좋은 화질의 영상으로써 표현할 수 있어야 한다. 본 논문에서는 고해상도, 고계조 모바일 디스플레이를 대상으로 소비 전력을 줄이면서도 디스플레이 시스템 내의 데이터 전송 속도를 증가시키고 시스템 구성을 간단하게 하여 가격 경쟁력을 갖춘 새로운 고속 인터페이스 방식 및 입출력 회로를 제안한다. 또한 고해상도, 고계조 영상 표현을 위하여 화질을 개선시킬 수 있는 구동 방법을 제안하고, 제안한 구동 방법에 대한 정량적인 분석과 실험을 통해 그 성능을 검증한다. 본 논문에서는 디스플레이 인터페이스 시스템 구성을 간단하게 하고 제조 단가를 절감시키기 위하여 클록 신호 정보를 데이터 신호 내에 포함시켜 한 쌍의 차동 전송선만을 가지고 모든 데이터 및 클록을 전송할 수 있는 새로운 인터페이스 방식을 제안하였다. 제안한 인터페이스 방식은 일반적으로 800Mbps의 전송율을 갖는 직렬 데이터를 전송 및 복원할 수 있으며, 만약 제안한 인터페이스를 휴대용 디스플레이 장치에 적용시킨다면, VGA 또는 WVGA의 해상도를 갖는 디스플레이를 지원할 수 있다. 현재 상용화된 기술 중 하나인 MDDI와 비교하였을 때, 동일한 대역폭을 갖는 신호를 전송한다고 가정하면 제안한 인터페이스 방식이 전송선의 개수 및 소비전력 면에서 장점을 갖는다. 시뮬레이션 결과, 800Mbps의 대역폭을 갖는 데이터를 전송할 때 제안한 인터페이스 방식의 경우 한 쌍의 전송선이 필요하고 8.5mW의 소비전력 특성을 갖는 반면, MDDI는 세 쌍의 전송전이 필요하고 9.5mW의 소비전력 특성을 보인다. 또한, 제안한 인터페이스 방식에 적용하기 위한 수신단 회로를 제안하였다. LVDS, DVI, HDMI, mini-LVDS, MDDI, MIPI 같은 이미 상용화 되거나 표준화된 디스플레이 인터페이스 회로를 설계 하더라도, 각 인터페이스 표준이 정하는 규격을 만족시키기 위해서는 설계가 모두 제각각 이루어져야 한다. 따라서 본 논문에서는 인터페이스 회로를 설계하는데 드는 시간 및 노력을 줄이기 위하여 대부분의 인터페이스 방식에 모두 적용할 수 있는 범용 인터페이스 수신단 회로를 제안한다. 제안한 수신단 회로는 내부에 셀프-리셋 기능을 하는 부궤환 루프를 포함하고 있는데, 이 부궤환 루프에 의해 데이터에 따른 지터 성분의 감소, 주파수 대역폭의 증가 및 소비전력의 감소 효과를 얻을 수 있다. 제안한 범용 인터페이스 수신단 회로는 0.18μm CMOS 공정을 이용하여 제작 및 측정하였다. 측정 결과, 29-1 PRBS 입력 신호에 대한 출력 신호의 지터 성분이 단위 비트 시간의 15% 이하로 나타났으며, 1.6Gbps의 신호를 복원하는데 4mW의 전력을 소비함으로써 기존의 인터페이스 수신단 회로와 비교하여 40% 이상의 소비전력 절감 효율을 보인다. 디스플레이 구동에 있어 또 다른 도전 과제 중 하나는 고해상도, 고계조 영상을 왜곡 없이 디스플레이 할 수 있는 구동 기술의 개발이다. 평판 디스플레이 구동 드라이버 IC의 경우 구조적으로 각 채널마다 출력 버퍼를 가지고 있는데, 이 출력 버퍼가 가지고 있는 오프셋 성분으로 인해 화질이 저하된다. 이와 같은 오프셋을 보상 또는 제거하기 위한 다양한 회로 기술들이 제안되었지만, 기존의 회로 기술만으로는 화질의 열화를 방지하는데 한계가 있다. 따라서, 본 논문에서는 각 채널의 출력 버퍼가 가지고 있는 오프셋 성분을 평균함으로써 채널간 오프셋 편차를 줄이는 구동 방법 및 구동 회로를 제안한다. 이러한 시스템적인 접근은 기존의 회로 기술을 대체하거나 또는 회로 기술과 함께 사용할 수 있는 새로운 대안이 될 것으로 기대된다. 제안한 구동 방법에 대하여 정량적인 분석을 하였고, 그 결과 제안한 구동 방식을 적용할 경우 공간적인 저대역 통과 필터 특성을 보이는 것을 확인하였다. 또한, 다수의 출력 채널을 공유하여 평균할수록 채널간 편차가 줄어드는 효과가 증대되기는 하지만 플리커가 발생하기 시작하는 경우와 회로의 복잡도를 고려하면 각 출력 채널당 해당 채널 및 양 옆 컬럼의 채널을 공유하는데 3개의 채널을 공유하는 것이 적당하다는 결론을 도출하였다. 제안한 구동 방법은 AMOLED 구동 IC에 적용되었고, 0.18μm CMOS 공정을 이용하여 설계되었다. 제작된 IC를 AMOLED 패널에 장착하여 실험한 결과, 채널간 출력 편차로 인해 화면에 보여지던 줄무늬 잡음 성분이 제안한 구동 방식에 의해 구동되는 동안에는 사라지는 것을 확인하였다.

      • Characteristics of La-incorporated TiN and Ru-based metal gates on Hf-based gate dielectrics for CMOSFETs

        김효겸 서울대학교 융합과학기술대학원 2013 국내박사

        RANK : 247807

        The minimum feature size, including gate oxide thickness, of complementary metal oxide semiconductor field effect transistors (CMOSFETs) has decreased exponentially until now. However, with this method, scaling slows down at the 90 nm node as SiO2 runs out of atoms and further scaling is limited due to the increase of gate-leakage current. To continue the scaling of transistors, various high-k oxide materials have been studied intensively for the past few decades. The semiconductor industry has already converged on Hf-based oxides for the first generation CMOS products featuring high-k gate dielectrics and metal gate electrodes. However, even though various metal materials were already used on Hf-based oxides, there are still several crucial problems that need to be considered; an effective work function (EWF) modulation for adjusting the threshold voltage (Vt) of transistors and further scaling of equivalent oxide thickness (EOT), which was approximately 1.0 nm for the first generation high-k/metal gate device. Continued gate length (Lg) scaling for the 32 nm and beyond with a planer structure requires sub-nm EOT to suppress short-channel effects. Fully depleted device structures, such as FinFET or extremely thin SOI (ETSOI), improve short-channel control and thus relax the requirements for EOT scaling. However, the insertion point of such device architectures is expected to be the 22 nm and beyond and sub-nm EOT may be still required at those advanced technology nodes. To meet continued EOT scaling until the turning point in device architectures, mainly three possible EOT scaling approaches are studied in this work: (1) a high-k material with k-value greater than that of HfO2 (so-called “higher-k”), (2) the physical thickness reduction of interfacial layer (IL) (so-called “scavenging”), (3) suppression of low-k dielectric layer between metals and dielectrics (so-called “deadlayer effect”). Firstly, the relation between the permittivity and microstructures of atomic layer deposited Hf1-xSixOy (HfSiO) thin films with different Si concentrations as a function of post-deposition annealing (PDA) temperature was investigated. The PDA at high temperature results in the separation of crystallized HfO2 phase from the much higher Si-containing amorphous-like matrix. Tetragonal phase HfO2 formation with higher permittivity than the monoclinic HfO2 phase is induced with an appropriate Si concentration in the film (~10–20%). In the crystallized HfSiO film, the Si concentration in the phase-separated HfO2 (mainly consisting of HfO2) could be controlled by PDA temperature, which determines the degree of phase separation. The increased PDA temperature reduces the Si concentration in the phase-separated HfO2 which induced monoclinic phase formation. Therefore, the PDA temperature for maximized permittivity of the crystallized HfSiO films (maximized tetragonal phase portion in the film) depends on the Si concentration of the HfSiO film in the as-deposited state. However, considering the maturity of Hf-based high-κ gate dielectrics, scaling SiO2-based IL in conjunction with Hf-based oxides may be more practical in meeting the requirements for the 22 nm technology node and beyond. Secondly, lanthanum (La)-incorporated TiN metal gates, such as TiN/La/TiN (TLT) and TiLaN (TLN), on HfO2/Si substrates were investigated focusing on the flat band voltage (VFB) modulation for nMOS and IL scaling to almost zero. The maximum VFB modulation value of the TLT/HfO2/Si stack was −423 mV compared to the VFB of the TiN single metal case, which is superior to that of TLN (−247 mV). This is because the TiN barrier layer in the TLT metal stack prevents interfacial oxidation. Both TLT and TLN gate metals effectively shrink the IL thickness to values below 0.5 nm. In the case where the TLT metal gate was annealed at 600 oC for 30s, the IL thickness was almost zero and the equivalent oxide thickness (EOT) was decreased to 0.8 nm even though the maximum temperature was limited to 600oC. However, the La-incorporated TiN metal gates can not adopt for pMOS due to their low work function, and another method must be pursued to scale the EOT of p-type MOSFET. Thirdly, the influences of RuO2 metal gate on the dielectric performance of high-k HfO2 film on Si substrate were examined. Dielectric materials with a higher-k value also suffer from a dead-layer effect that the effective dielectric constant decreases with decreasing thickness, which becomes even more serious as the bulk k value increases. The EOT of HfO2 film can be scaled down by ~ 0.5 nm in the EOT range from 0.8 to 2.5 nm compared with the standard Pt gate case by using the electrically conducting RuO2 without sacrificing any other performance of the MOS capacitor. RuO2 is one of the rare materials, which contain polarizable ions, high electrical conductivity, and high work function (WF) which is necessary for the p-type MOSFET. This was attributed to the suppression of the dielectric dead-layer effect at the HfO2/RuO2 interface due to the possible ionic polarization of RuO2 within the screening length of the electrode. In addition, the estimated work function of RuO2 on HfO2 is ~ 5.0 eV suggesting the appropriateness of RuO2 for p-MOSFET. Finally, RuO2 metal gates were fabricated by a reactive sputtering method under the different O2 gas ratio. For the given sputtering power of 60 W, ~ 13 % O2 ratio was the critical level below or over which RuO2 film have hyperstoichiometric and stoichiometric compositions, which resulted in the effective work function difference by ~ 0.2 eV. The stoichiometric RuO2 film imposed almost no damaging effect to the underlying SiO2 and HfO2 gate dielectrics. RuO2 gate decreased the equivalent oxide thickness by ~ 0.5 nm and leakage current by ~ two orders of magnitude compared with the Pt-gated samples.

      • Direct tensile behavior of ultra-high-performance fiber-reinforced concrete subjected to impact loading

        Tran, Ngoc Thanh Sejong University 2016 국내박사

        RANK : 247807

        Ultra-high-performance fiber-reinforced concrete (UHPFRC) is much expected to enhance the resilience and sustainability of civil infrastructure under impacts or blasts owing to its outstanding tensile properties including high strength, ductility and energy absorption capacity at static rate; however, its tensile response at high strain rate is still not well understood. In order to fill the knowledge gap, the objective of this research is to develop better understanding of UHPFRC tensile response at high strain rates. The research is divided into three parts, as follows: In first part, the direct tensile stress versus strain response of UHPFRCs at high strain rates (5 to 24 /s) was investigated. UHPFRCs exhibited tensile strain hardening behavior even at high strain rates and especially their tensile behavior was found to be very sensitive to the applied strain rates. The tensile behavior of UHPFRCs at high strain rates was much influenced by the size of specimen and fiber type. Unlike at static rate, UHPFRCs with smooth fibers produce higher tensile properties than those with twisted fibers at high strain rates. In second part, the fracture energies including peak toughness and softening fracture energy of UHPFRCs at high strain rates (5–92 /s) was investigated and the UHPFRCs with 11.5% of fibers volume contents exhibited very high entire fracture energy (2871 kJ/m2) at high strain rates. The peak toughness was highly sensitive to strain rate whereas the softening fracture energy was not. In the investigation of UHPFRCs fracture energies, the un-notched specimens were more suitable than notched specimens. The effects of fiber type and fiber volume on the UHPFRCs fracture energies were found to be totally different between at static rate and at high strain rates. Finally, a method for enhancing the tensile resistance of UHPFRCs at high strain rates (16 – 37 /s) was proposed by blending long and short steel fibers. UHPFRCs blending small volume content of long and short steel fibers (total 1.5%) produced very high tensile resistance at high strain rates: post cracking strength up to 32.6 MPa, strain capacity up to 1.87%, peak toughness up to 412.6 kJ/m3 and softening fracture energy up to 31.3 kJ/m2. In particular, UHPFRCs with fibers blending, based on the synergistic performance, produced 86.4% higher strain capacity and 72.2% higher peak toughness than normal UHPFRCs with mono steel fibers. The strain rate sensitivity model in tension of UHPFRCs based on the best fit of experimental test results was proposed and the tensile resistance of UHPFRCs was predicted even at high strain rates.

      • HIGH-LEVEL FUNCTION AND DELAY TESTINGFOR DIGITAL CIRCUITS

        이준환 University of Michigan 2002 해외박사

        RANK : 247807

        Conventional low-level (gate-level) testing methods are not well suited to circuits with modules whose implementation details are unknown, such as systems-on-a-chip (SOCs). SOCs extensively reuse large pre-designed and verified intellectual property (IP) circuits, also known as cores, to shorten time-to-market. IP circuits are usually provided by third-party vendors, and their implementation details are often hidden from designers. Most existing SOC testing methods reuse pre-computed test sets for IP circuits, as well as design-for-test (DFT) techniques. However, for high-performance or high-density SOCs, the added area and performance overhead due to DFT circuits is not tolerable. On the other hand, high-level testing methods can generate tests from high-level (more abstract) descriptions of IP circuits, and apply the tests without the DFT circuits needed for test set reuse. In this dissertation, we propose a high-level testing approach for both function and delay faults to address SOC testing problems. Two new high-level fault models, the coupling fault (CF) model and the coupling delay fault (CDF) model, are introduced. The corresponding test sets are defined and related to other low- and high-level test sets. It is shown that (reduced) coupling test sets are smaller than the so-called universal test sets, but still achieve very high stuck-at fault coverage for a broad range of implementations. The coupling delay test set we propose is smaller than other existing high-level delay test sets, and detects all robust path delay faults in any realization of the target function. A high-level delay test generation method for modular circuits is developed to reduce test set size. Experimental results are presented which demonstrate that significant reduc-tion in test set size can be achieved by taking advantage of circuit hierarchy. A small but powerful high-level robust delay test set is derived from the coupling delay test set using dominance relationships. The application of robust coupling delay test sets to modular circuits provides better coverage of delay faults. Our experiments confirm that significant reduction in test set size can be achieved by using the new test set instead of the coupling delay test set.

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