심층 신경망을 활용한 자동 영상 잡음 제거 기법

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 협동과정 계산과학전공, 2020. 8. 강명주.Noise removal in digital image data is a fundamental and important task in the field of image processing. The goal of the task is to remove noises from the given degraded images while maintaining essential details such as edges, curves, textures, etc. There have been various attempts on image denoising: mainly model-based methods such as filtering methods, total variation based methods, non-local mean based approaches. Deep learning have been attracting significant research interest as they have shown better results than the classical methods in almost all fields. Deep learning-based methods use a large amount of data to train a network for its own objective; in the image denoising case, in order to map the corrupted image to a desired clean image. In this thesis we proposed a new network architecture focusing on white Gaussian noise and real noise cancellation. Our model is a deep and wide network designed by constructing a basic block consisting of a mixture of various types of dilated convolutions and repeatedly stacking them. We did not use a batch normal layer to maintain the original own color information of each input data. Also skip connection was utilized so as not to lose the existing information. Through several experiments and comparisons, it was proved that the proposed network has better performance compared to the traditional and latest methods in image denoising.디지털 영상 데이터 내의 잡음 제거 및 감소는 열화된 영상의 노이즈를 제거하면서 모서리, 곡선, 질감 등과 같은 필수 세부 정보를 유지하는 것이 목적인 영상 처리 분야의 기본적이고 필수적인 작업이다. 딥러닝 기반의 영상 잡음 제거 방법들은 열화된 영상을 원하는 품질의 영상으로 매핑하도록 대용량의 데이터를 이용하여 네트워크를 지도학습하며 고전적인 방법들보다 뛰어난 결과를 보여주고 있다. 본 논문에서는 이미지 디노이징에 대한 여러 방법들을 조사했을 뿐만 아니라, 특히 백색 가우시안 잡음과 실제 잡음 제거 문제에 집중하면서 네트워크 아키텍처를 설계하고 실험하였다. 여러 형태의 딜레이티드 콘볼루션들을 혼합하여 기본 블록을 구성하고 이를 반복하여 쌓아서 설계한 네트워크를 제안하였고, 각각 본연의 색상을 유지할 수 있도록 여러 입력 영상을 하나로 묶어 구성하는 배치를 평준화하는 배치노멀 레이어는 사용하지 않았다. 그리고 블록이 여러 층 진행되는 동안 기존의 정보를 손실하지 않도록 스킵 커넥션을 사용하였다. 여러 실험과 기존에 제안된 방법과 최신 벤치 마크와의 비교를 통하여 제안한 네트워크가 노이즈 감소 및 제거 작업에서 기존의 방법들과 비교하여 우수한 성능을 가지고 있음을 입증하였다. 하지만 제안한 아키텍처방법의 한계점도 몇 가지 존재한다. 제안한 네트워크는 다운샘플링을 사용하지 않음으로써 정보 손실을 최소화하였지만 최신 벤치마크에 비하여 더 많은 추론 시간이 필요하여 실시간 작업에는 적용하기가 쉽지 않다. 실제 영상에는 단순한 잡음보다는 영상 획득, 저장 등과 같은 프로세스를 거치면서 여러 요인들로 인한 다양한 잡음, 블러와 같은 열화가 혼재 되어 있다. 실제 잡음에 대한 다양한 각도에서의 분석과 여러 모델링 실험, 그리고 영상 잡음 및 블러, 압축과 같은 복합 모델링이 필요하다. 향후에는 이러한 점들을 보완함으로써 성능을 향상시키고 네트워크의 조정을 통해 실시간으로 적용될 수 있음을 기대한다.1 Introduction 1 2 Review on Image Denoising Methods 4 2.1 Image Noise Models 4 2.2 Traditional Denoising Methods 8 2.2.1 TV-based regularization 9 2.2.2 Non-local regularization 9 2.2.3 Sparse representation 10 2.2.4 Low-rank minimization 10 2.3 CNN-based Denoising Methods 11 2.3.1 DnCNN 11 2.3.2 FFDNet 12 2.3.3 WDnCNN 12 2.3.4 DHDN 13 3 Proposed models 15 3.1 Related Works 15 3.1.1 Residual learning 15 3.1.2 Dilated convolution 16 3.2 Proposed Network Architecture 17 4 Experiments 21 4.1 Training Details 21 4.2 Synthetic Noise Reduction 23 4.2.1 Set12 denoising 24 4.2.2 Kodak24 and BSD68 denoising 30 4.3 Real Noise Reduction 34 4.3.1 DnD test results 35 4.3.2 NTIRE 2020 real image denoising challenge 42 5 Conclusion and Future Works 46 Abstract (in Korean) 54Docto

한국 대도시 소방관들의 유해물질 직접, 간접 노출과 질병유병률

학위논문 (박사) -- 서울대학교 대학원 : 보건대학원 보건학과(보건학전공), 2021. 2. 성주헌.서론 : 세계보건기구 산하 국제암연구소에서는 소방관의 직업적 노출을 인체발암가능인자인 그룹2B로 생체리듬 교란인자인 교대근무를 발암추정인자인 그룹2A로 규정하고 있다. 이외에도 소방관은 재난 등 소방활동현장에서 노출되는 위험물질에 의해서도 발암물질에 추가적으로 노출될 수 있다. 소방관의 직업환경은 출동현장, 출동경로, 사무공간으로 분류된다. 특히, 출동현장 중 하나인 화재현장에서 발생하는 일산화탄소, 시안화수소, 포름알데히드 등 10여종의 각종 독성물질은 인체 건강영향을 주는 강력한 위험인자 중 하나인 것으로 잘 알려져 있다. 소방관들은 재난현장에서 발생하는 위험요인에 지속적으로 노출됨으로써 질병부담을 증가시킨다. 따라서, 소방관의 근무환경과 재난현장 직업환경에 대한 위험요인에 대한 정보가 있다면, 예측가능한 건강영향을 예방할 수 있을 것이다. 본 연구의 목적은 대도시에 근무하는 소방관들의 출동현장과 사무공간에 대한 직업환경을 측정하고 방화복 사용, 세척, 관리에 대한 보건학적 인식을 평가한다. 더불어 대도시 소방관 전수코호트를 대상으로 특수건강진단결과를 이용하여 일반인구집단과 만성병과 직업관련성 질환의 표준화 유병률(비)를 비교 평가함으로써 건강수준을 평가한다. 방법 : 첫 번째 연구는, 서울시에 근무하는 화재진압과 인명구조 업무를 수행하는 소방관 1,097명을 대상으로 21일간 설문조사를 실시하여 40.3%의 응답률을 보였다. 이 조사에서 소방관들이 사용하는 개인보호장비 중 하나인 방화복의 사용, 세탁, 관리정도와 보건학적 인식간에 연관성을 평가하였다. 또한, 소방관들의 직업환경 중 하나인 재난현장 활동단계를 평가하였다. 국내에서 가장 많은 발생을 보이는 주택화재 발생을 직업환경으로 화재현장에서 1차적으로 발생하는 오염과 2차적으로 발생하는 방화복 교차오염에 대하여 오염물질의 종류와 양에 대하여 실험을 하였다. 교차오염 평가는 방화복을 직업환경의 위험정도에 따라 4개 그룹으로 나누어 측정하였다. 이때 1차오염과 2차오염에서의 공기포집을 통해 12개 항목을 분석하였다. 또한, 방화복에 묻은 오염물질은 세탁물을 추출하여 24개 항목에 대하여 수질분석을 수행하였다. 설문조사와 실험연구를 통해 도출된 문제점에 대한 대책마련을 위하여 델파이 전문가 조사 방법으로 실행가능성과 효과성을 높일 수 있는 구체적인 정책을 제안하였다. 델파이 전문가 조사의 참여대상자는 소방현장과 방화복에 대한 선험적 실무경험과 연구경험이 많은 대학교수와 소방관을 7명을 대상으로 3라운드에 걸쳐 수행하였다. 두 번째 연구는, 소방관들의 직업환경 중 하나인 근무 중 대기공간인 소방청사 내에서의 근무환경을 평가하였다. 소방관들이 화재현장에서 철수하여 소방서로 복귀한 후 소방청사 내부와 소방차량에서 2차적으로 노출되는 화학적 유해물질의 실내공기질을 평가하였다. 서울시 소재 4개소방서를 무작위로 선정하였다. 2개소는 실험군으로 화재현장 소방활동이 종료되고 소방서로 귀소한 후에 측정하였다. 다른 2개소는 대조군으로 출동과 상관없이 평소 수준에서 실내공기질을 측정하였다. 소방안전지도 전산시스템을 이용하여 서울시에서 발생하는 모든 화재사고를 24시간 모니터링하였고, 중급규모 이상의 사고에서 실험군이 출동하게 되는 경우 귀소 후 바로 실내공기질을 측정하였다. 11개 유해물질항목(미세먼지, 포름알데히드, 휘발성유기화합물, PAH, VCM, 산류, 석면, CO, CO2, NO2, O3)은 공정시험법에 따라 측정하였다. 세 번째 연구는 위험직군 중 하나로 분류되어 있는 소방관은 예측 불가능한 유해물질에 지속적, 반복적으로 노출되고 있으나 건강관리는 개인적 의무로 간주되고 있다. 따라서 본 연구에서는 매년 실시하는 소방관 특수건강진단 결과자료를 이용하여 대도시 소방관들의 만성질환인 고혈압, 당뇨, 대사증후군, 비만과 직업성 질환인 폐 환기장애(제한성, 폐쇄성, 복합성)와 소음성난청(4분법, 6분법)에 대하여 일반인구집단의 국건영 검진결과를 이용, 비교하여 직접표준화 방법으로 소방관과 일반인구집단 1,000명당 성-연령 표준화유병률과 간접표준화 방법으로 성-연령 표준화 유병비를 각각 산출하였다. 또한, 소방관 특수건강진단결과에 대한 역학적 특성을 분석하였다. 결과 : 첫 번째 연구에서, 소방관들은 재난현장에서 발암물질 발생가능성 인지도는 94.4%로 높았다. 이러한 보건학적 사고가 소방관 스스로의 안전을 지켜주는 방화복의 사용, 세탁, 관리에 대한 행동에는 영향을 주지 않는 것으로 확인되었다. 다만, 방화복의 사용에서, 화재현장에서 소방활동 종료 후 방화복을 실제 벗어야 하는 위치에 대한 생각과 보건학적 사고간에는 연관성이 있었다 (AOR=1.92, CI 1.01-3.68). 화재현장과 방화복 오염도 평가결과, 화재현장에서는 급성 피부독성을 유발하는 시안화수소가 불완전연소(훈소화재)와 완전연소(화염화재) 모두에서 검출되었다. 시안화수소는 방화복 포집공기에서도 검출되어 화재현장에서의 방화복 착용이 매우 중요함을 확인하였다. 포름알데히드는 완전연소(화염화재)에서 노출기준 TWA 0.3을 초과하여 방화복에서 검출되었다. 이 외에도 시안화수소, 니켈은 신규 배정받은 방화복에서도 검출되었으나 위험수준을 초과하지는 않았다. 시안화수소는 방화복 모든 실험그룹에서 검출되었고, 납, 산화철, 알루미늄, 카드뮴과 같은 중금속 물질도 공기포집에서 검출되었다. 방화복 교차오염 수질분석 결과에서는 구리, 니켈, 아연 등의 중금속이 발견되었다. 아크릴로니트릴은 화재에 한 번 노출된 경우보다 연속으로 노출된 경우 그 양이 2.1배 더 높은 양-반응관계를 보였다. 1급 발암물질인 나프탈렌은 훈소화재와 화염화재 모두 검출되었으나 훈소화재에서 더 높게 검출되었다. 구리와 그 화합물, 안티몬, 아크릴로니트릴, 디에틸헥실프탈레이트 4개 항목이 물환경보존법 기준 특정수질유해물질 폐수배출시설 적용기준을 초과하여 검출되었다. 이로써 화재현장에서의 방화복 오염이 심각함을 확인하였고 수질오염 가능성을 시사하였다. 또한, 상기 4개 항목이 폐수기준치를 초과하여 검출됨으로써 중재가능성 또는 정책적 조치가 필요함을 확인하였다. 설문조사와 실험연구에서 도출된 문제의 대안마련을 위하여 델파이조사를 수행한 결과, 설문조사와 화재현장과 방화복 오염도 실험결과를 중요도 부문에서는 소관분야 예산확보와 재난현장 오염물질 건강영향 위험성에 대한 교육실시가 가장 시급한 과제로 평가되었다. 실행가능성 부문에서는 재난현장 오염물질의 건강영향 위험성 교육실시, 개인보호장비 1차제염 교육실시, 방화복 등 개인보호장비 관리체계 개선과 체계적 운영을 위한 교육과정 개발이 가장 시급한 과제로 평가되었다. 두 번째 연구에서, 소방청사에서 측정한 유해물질 11종 중 3종이 국내•외 기준을 초과하였고, 1종은 국외기준에 육박하는 것으로 확인되었다. 특히 총휘발성유기화합물, 이산화탄소, 황산은 각 2.5배, 2.2배, 1.1배가 환경부와 고용노동부 기준보다 높았다. 또한, 포름알데히드와 황산의 경우, 실험군보다 대조군에서 더 높게 측정되었다. 세 번째 연구에서, 대도시 소방관 특수건강진단결과 전수자료를 이용하여 일반인구집단과 비교를 통해 직접표준화 방법으로 산출한 질병단계의 성-연령보정 표준화 유병률은 소방관에서 대사증후군 12.43% (남 16.91%, 여 7.76), 폐환기장애에서, 제한성은 16.87% (여 18.32%), 복합성은 2.07% (여 2.59%) 일반인구보다 높았다. 일반인구는 고혈압 17.93% (남 23.44%, 여 12.19%), 당뇨 5.30% (남 6.75%, 여 3.80%), 비만 34.29% (남 46.94%, 여 21.14%), 폐환기장애의 경우, 폐쇄성에서 4.39% (남 6.13%, 여 2.61%), 소음성 난청의 경우, 3분법에서 우측은 4.41% (남 5.51%, 여 3.29%), 좌측은 4.87% (남 6.41%, 여 3.29%) 이었고, 4분법에서 우측은 6.99% (남 8.66%, 여 5.28%), 좌측은 7.92% (남 10.06%, 여 5.71%) 소방관보다 높았다. 각 질환의 질병전단계 성-연령보정 표준화 유병률은 고혈압 37.26% (남 52.45%, 여 21.47%), 당뇨 23.17% (남 30.79%, 여 15.25%), 대사증후군 87.21% (남 83.09%, 여 91.49%), 비만 23.25% (남 33.08%, 여 13.03%)로 일반인구보다 소방관에서 모두 높았다. 또한, 간접표준화에 의한 표준화 유병비에서는, 질병단계의 경우, 일반인구보다 소방관에서 비만 1.12배 (1.08-1.16), 대사증후군 1.33배 (1.26-1.40) 높았고, 질병전단계의 경우, 소방관에서 비만 1.34배 (1.29-1.40), 고혈압 1.89배 (1.83-1.96), 당뇨 1.36배 (1.31-1.41), 대사증후군 1.85배 (1.81-1.90) 일반인구보다 높았다. 결론 : 방화복 설문조사를 통해 소방관의 보건학적 생각과 방화복의 사용, 세탁, 관리행동간에는 연관성이 없었으나, 보건학적 생각과 방화복의 올바른 사용에 대한 생각 사이에는 연관성통계적 유의성을 보여 생각에서 행동으로 옮길 수 있는 통로를 마련해주는 것이 필요하여 이에대한 대책마련이 필요하다. 주택화재에서 발생할 수 있는 화재현장과 방화복 오염물질 발생 실험을 통해 재난현장에서의 소방관 직업환경을 평가하였다. 우리는 본 연구결과를 통해 주택화재에서 발생할 수 있는 유해물질의 종류와 양을 추정할 수 있었다. 물론 제한된 공간에서 발생한 유해물질의 종류와 양으로 과소추정 가능성이 있으나, 이 연구결과를 토대로 일반적으로 주택화재 현장에서 발생하는 유해물질의 종류와 양에 대한 DB를 구축할 수 있을 것이며, 화재현장에서 개인보호장비의 정확하고 철저한 착용이 중요함을 재확인하였다. 더불어, 방화복 오염에 의한 수질오염의 가능성 확인을 통해 후속연구와 정책실행이 필요함을 확인하였다. 또한, 소방관의 근무년수와 출동횟수에 대한 정보가 있다면 토대로 주택화재현장에서 노출되었던 유해물질의 누적노출양을 산정할 수 있을 것이다. 이러한 자료들은 소방관에게 질병이 발생하였을 때 업무관련성 질환여부를 입증할 수 있는 근거자료로 활용할 수 있을 것이다. 또한, 화재현장에서 교차오염이 발생한 방화복에 대하여 현장 긴급제염에 대한 소방정책을 실행하기 위한 강력한 과학적 근거를 제공할 수 있을 것이다. 본 연구결과는 소방관 방화복 안전한 사용과 보건정책을 추진할 때 적극 활용할 수 있을 것이다. 소방청사 실내공기질 평가를 통해 소방관 대기근무환경에 대한 직업환경 측정을 수행하였고, 실내공간과 차고에서 기준을 초과하는 항목들이 검출되었다. 또한, 재난현장 출동 후 귀소와 상관없이 소방차량 배기가스와 평소 화학적 유해물질의 누적이 청사 내 실내공기질 뿐만 아니라 장•단기적으로 소방관의 건강영향에 문제를 줄 수 있는 가능성이 있어 소방청사의 체계적 실내공기질 관리가 필요함을 확인하였다. 본 연구결과는 향후 서울시 소방청사 내 실내공기질 관리시스템이 정착과 개선에 활용될 수 있을 것이다. 마지막으로, 특수건강진단결과 분석을 통한 소방관과 일반인구집단과의 표준화 유병률 비교를 통해 질병단계의 경우, 건강근로자 효과가 있음을 추정할 수 있었다. 그러나 질병전단계의 경우 소방관에서 모든 만성질환에서 일반인구보다 높은 유병률을 보임에 따라 체계적인 건강관리 프로그램이 필요함을 확인하였다. 특히, 건강근로자 효과를 보이는 직군에서는 검진결과의 코호트 구축을 통한 연구를 통해 체계적인 추적, 관리시스템 구축이 필요하다. 끝.Introduction : The International Cancer Institute (IARC) under the World Health Organization regulates the occupational exposure of firefighters as group 2B, which is a possible human carcinogenic factor, and group 2A, which is a predicted carcinogenic factor, as the shift work, a factor that disturbs the biological rhythm. In addition, firefighters may be additionally exposed to carcinogens by dangerous substances exposed at fire fighting scene such as disasters. The firefighter's work environment is classified into dispatch scene, emergency response route, and office space. In particular, 10 kinds of toxic substances, such as carbon monoxide, hydrogen cyanide, and formaldehyde, which are generated at the fire scene, which is one of the dispatch scenes, are well known to be one of the strong risk factors that affect human health. Firefighters increase the burden of disease by constantly being exposed to risk factors occurring at the disaster scene. Therefore, if there is information on the risk factors for firefighters' working environment and disaster scene work environment, predictable health effects can be prevented. The purpose of this study is to measure the working environment of firefighters working in metropolitan in the dispatch scene and office space, and to evaluate the health perception of health. In addition, the standardized prevalence rate (ratio) of chronic diseases and work-related diseases is compared and evaluated with the general population with the general population using the results of occupational health examinations targeting the total cohort of firefighters in metropolitan cities to evaluate their health level. Methods : First, a survey was conducted for 1,097 firefighters working in the city of Seoul for fire fighting and rescue work for 21 days, with a response rate of 40.3%. In this survey, health awareness was evaluated on the use, washing, and management of fire fighting protection suit, one of the personal protective equipment used by firefighters. In addition, the level of activity at the disaster scene among firefighters' work environments was evaluated. In the work environment, the most common occurrence of residential fires in Korea was tested for the type and amount of pollutants for the primary contamination and secondary cross-contamination of fire fighting protection suit. Cross-contamination evaluation was measured by dividing fire clothing into 4 groups according to the degree of risk of the work environment. At this time, 12 items were analyzed through air sampling in the primary and secondary contamination environment. In addition, the contaminations on the fire fighting protection suit were extracted from the laundry water and water quality analysis was performed on 23 items. In order to prepare countermeasures for problems derived through questionnaire surveys and experimental studies, a specific policy that can increase the feasibility and effectiveness of the Delphi expert survey method was proposed. Participants in the Delphi expert survey conducted three rounds of university professors and firefighters with a priori practical experience and research experience on firefighting scenes and firefighting suits. Second, firefighters evaluated the working environment at the fire station, a waiting space during work. After firefighters withdrew from the fire scene and returned to the fire station, the indoor air quality of the chemically hazardous substances that were secondarily exposed inside the fire station was evaluated. The research subject randomly selected four fire stations located in Seoul, Korea. The two fire stations were measured after the firefighting activities at the fire scene were terminated and returned to the fire station as an experimental group. The other two sites were controls, and the indoor air quality was measured at the usual level regardless of dispatch. We conducted 24-hour monitoring for all fire accidents that occurred in Seoul Metropolitan using fire safety map computer system. Also, indoor air quality was measured immediately after homecoming if the experiment group was to be dispatched due to an accident of intermediate or larger scale. 11 hazardous substance items such as particulate matter, formaldehyde, volatile organic compounds, PAH, VCM, acidity, asbestos, CO2, NO2, O3 were measured according to the process test method. Thirdly, firefighters classified as one of the dangerous occupations are exposed to unpredictable hazardous substances, but health management is considered a personal obligation. Therefore, in this study, using the results of annual firefighters' occupational health examination, high blood pressure, diabetes mellitus, metabolic syndrome, obesity and work-related diseases such as pulmonary ventilation disorders (limited, obstructive, combined) and noise-induced hearing loss (three tone average and four tone average method). The age- and sex-adjusted standardized prevalence rate per 1,000 firefighters was calculated using the direct standardization method and the age- and sex-adjusted standardized prevalence ratio by the indirect standardization method. Results : In the first study, firefighters had a high 94.4% awareness of the possibility of carcinogens occurring at the disaster scene. It was confirmed that these health awareness did not affect the behavior of the use, washing, and maintenance of fire fighting protective suit that protects their own safety. However, in the use of fire fighting protection suit, there was statistical significance between the thought of the location where fire fighting protection suit should be taken off after the firefighting activity at the fire scene and the health awareness. As a result of the fire scene and fire fighting protection suit contamination assessment, hydrogen cyanide, which causes acute skin toxicity, was detected in both incomplete and complete combustion at the fire scene. Hydrogen cyanide was also detected in the air sampled in fire fighting protection suit, confirming the importance of wearing fire fighting protection suit at the fire scene. Formaldehyde was detected in fire fighting protection suits exceeding the exposure limit TWA 0.3 in complete combustion. In addition, hydrogen cyanide and nickel were detected in newly allocated fire protection clothing, but did not exceed the risk level. Hydrogen cyanide was detected in all experimental groups in fire fighting protection suit, and heavy metals such as lead, iron oxide, aluminum and cadmium were also detected in air sampling. In the results of water quality analysis for cross-contamination of fire fighting protection suit, four items of copper and its compounds, antimony, acrylonitrile, and diethylhexylphthalate were detected in excess of the standards applied to wastewater discharge facilities for specific water quality hazardous substances according to the Water Environment Conservation Act in Korea. As a result, it was confirmed that the contamination of fire fighting protection suit at the fire scene was serious and suggested the possibility of water pollution. In addition, it was confirmed that policy measures were necessary as four items were detected exceeding the wastewater standard. The most urgent task was to secure the budget for the relevant field and conduct education on the risk of health impact of contaminations in the disaster scene in the importance category of the questionnaire survey and the results of the fire scene and fire fighting protection suit contamination level test. In the field of feasibility, education on the risk of health impacts of pollutants at disaster scenes, first-line decontamination education for personal protective equipment, improvement of personal protective equipment management system such as fire fighting protection suit and development of a curriculum for systematic operation were evaluated as the most urgent tasks. In the second study, it was confirmed that three of the 11 hazardous substances measured by the fire department exceeded the domestic and foreign standards, and one was close to the international standards. In particular, total volatile organic compounds, carbon dioxide and sulfuric acids were 2.5 times, 2.2 times and 1.1 times higher than the standard. Also, for formaldehyde and sulfuric acid, it was measured higher in the control group than in the case group. In the third study, as a result of comparison with the general population using the data obtained from occupational health examinations for firefighters in metropolitan cities, the age- and sex- adjusted standardized prevalence rate at the disease stage was 12.43% (male 16.91%, female 7.76%) for metabolic syndrome in firefighters, and in pulmonary ventilation disorders, the restrictive was 16.87% (male 15.45%, female 18.32%), and the combined was 2.07% (female 2.59%), which was higher than that of the general population. The general population was hypertension 17.93% (male 23.44%, female 12.19%), diabetes mellitus 5.30% (male 6.75%, female 3.80%), obesity 34.29% (male 46.94%, female 21.14%), and in the case of pulmonary ventilation disorder, obstructive 4.39% (male 6.13%, female 2.61%), in the case of noise-induced hearing loss by three tone average, the right side was 4.41% (male 5.51%, female 3.29%), and the left side was 4.87% (male 6.41%, female 3.29%). In the four tone average, the right side was 6.99% (male 8.66%, female 5.28%), and the left side 7.92% (male 10.06%, female 5.71%) higher than that of firefighters. The age- and sex- adjusted standardized prevalence rate for each disease was hypertension 37.26% (male 52.45%, female 21.47%), diabetes mellitus 23.17% (male 30.79%, female 15.25%), metabolic syndrome was 87.21% (male 83.09%, female 91.49%) ), obesity was 23.25% (male 33.08%, female 13.03%), which was higher in all firefighters than the general population. In addition, in the standardized prevalence ratio by indirect standardization, in the case of the disease stage, the firefighters were obesity 1.12 times (95% CI 1.08-1.16) and the metabolic syndrome 1.33 times (1.26-1.40) higher than the general population. It was higher than that of the general population (1.29-1.40), hypertension 1.89 times (1.83-1.96), diabetes mellitus 1.36 times (1.31-1.41), and metabolic syndrome 1.85 times (1.81-1.90). Conclusions : There was no statistical significance between the firefighter's health awareness and the use, washing, and management behavior of firefighters through the fire fighting protection suit survey. However, there was statistical significance between the health awareness and the thoughts on the proper use of fire fighting protection suit. Therefore, it is necessary to provide a pathway to move from thought to action. Firefighters' working environment at the disaster scene was measured through experiments on the occurrence of contaminants in fire scenes and fire fighting protection suits that may occur in residential fires. Through the results of this study, we were able to estimate the types and amounts of hazardous substances that can occur in a residential fire. Based on the results of this study, it is possible to establish a database on the types and amounts of hazardous substances that generally occur at residential fire scenes. Furthermore, it was confirmed that follow-up research and policy implementation are necessary through confirmation of the possibility of water pollution due to contamination of fire fighting protection suit. Also, if there is information on the number of years worked and the number of dispatches of firefighters, the cumulative exposure amount of hazardous substances exposed at the residential fire scene can be calculated. These data can be used as evidence to prove whether a firefighter has a disease related to work when a disease occurs. In addition, it will be able to provide a strong scientific evidence for implementing firefighting policies for emergency decontamination on-scene for firefighting suits with cross-contamination at the fire scene. The results of this study can be actively used when promoting the safe use of firefighters' fire fighting protection suit and health policies. Through the evaluation of the indoor air quality of the fire station building, the work environment was measured for the firefighter's standby working environment, and items exceeding the standard were detected in the indoor space and garage. In addition, regardless of returning after dispatch to the disaster scene, the accumulation of fire fighting vehicle exhaust gas and usual chemically hazardous substances has the potential to affect not only the indoor air quality of the building, but also the health of firefighters in the long and short term. It was confirmed that air quality management was necessary. The results of this study suggest that the indoor air quality management system in the Seoul Fire Department can be used for settlement and improvement in the future. Finally, by comparing the standardized prevalence rate between firefighters and the general population through the analysis of the results of occupational health examination, it was possible to estimate that there is an effect of healthy workers in the case of the disease stage. However, in the case of the pre-disease stage, it was confirmed that a systematic health management program was necessary as firefighters showed a higher prevalence than the general population in all chronic diseases. In particular, it is necessary to establish a systematic tracking and management system through research through cohort establishment of examination results in occupational groups showing the effect of healthy workers.Chapter 1. Introduction 1 Chapter 2. Behavior Evaluation of Firefighters Turnout Gear Using, Management and Assessment of Direct & Cross Contamination through Chemical Pollutant Exposures after Fire Occurrence 24 1. Introduction 25 2. Goal of this study 30 3. Frame of study 31 Chapter 2.1. Association between Behavior of Using, Washing, Management of Turnout Gear and Public Health Awareness 33 1. Study Aims 33 2. Literature Reviews 33 3. Methods and Materials 36 4. Results 40 5. Discussion 55 Chapter 2-2. Assessment of Primary and Secondary Contamination of Chemical Pollutants on Fire fighting Protection Suit at Fire Scenes 60 1. Study Aims 60 2. Literature Reviews 60 3. Methods and Materials 66 4. Results 92 5. Discussion 105 Chapter 2-3. A Study on Delphi for Improving the Perception of Firefighting Suit Management and Alternative Policy for Reducing Contamination Level 109 1. Study Aims 109 2. Methods and Materials 109 3. Results 114 4. Discussion and Political Suggestions 128 4. Limitations and Strength 144 5. Conclusion 146 Chapter 3. Characterization of Secondary Exposure to Chemicals and Indoor Air Quality in Fire Station 148 1. Introduction 149 2. Study Objective 151 3. Methods and Materials 151 4. Results 159 5. Discussions 174 6. Limitations and Further study 184 7. Conclusions 186 Chapter 4. The Prevalence of Chronic Disease and Work-related Disease among Korean Firefighters compared with the General Population 188 1. Introduction 189 2. Study Objective 191 3. Methods and Materials 191 4. Results 205 5. Discussions 254 6. Conclusions 259 Chapter 5. Public Health Implications and Further Studies 261 1. Measurement of various occupational environments of firefighters 262 2. Firefighters health status assessment 264 References 266 국문초록 271Docto

Clinical Outcomes of Spousal Donor Kidney Transplantation: Single Center Experience

The supply of deceased donors is limited in Korea and most of kidney transplantations are performed using living related or unrelated donors. In this study, we investigated the clinical characteristics and outcomes of spousal donor kidney transplantation at our center. Methods: From January 2000 to August 2008, we performed 909 cases of kidney transplantations. In this study, 475 one-haplomatch living-related donor (LRD) and 50 spousal donor kidney transplantations were retrospectively analyzed. We compared the outcomes of spousal donor group with those of one-haplomatch LRD group. We also compared the outcomes of husband-to wife with those of wife-to-husband subgroup. Results: The number of Human leukocyte antigen (HLA) mismatch was significantly larger in spousal group (3.3±1.2) than in LRD group (2.7±0.7). The proportion of tacrolimus use was higher in spousal group (72.0%) than in LRD group (26.6%). The incidence rate of delayed graft function was higher in spousal group (4.0%) than in LRD group (0.4%). There was no significant difference in the incidence of acute rejection between the two groups. Graft survival rates in spousal group (98.0% at 1 year and 91.5% at 5 year) were comparable to those in LRD group (99.6% at 1year and 98.7% at 5 year) (P=0.321). There were no significant differences in the incidence of acute rejection and graft survival rates between the subgroups (husband-to-wife vs. wife-to- husband). Conclusions: We achieved excellent outcomes by using spousal donor as an option to reduce the donor organ shortageope

리더—멤버 갈등 비대칭 현상의 개인의 창의성에 대한 효과

학위논문 (석사)-- 서울대학교 대학원 : 경영학과, 2017. 2. 최진남.We examine the effects of an overlooked concept of leader-member conflict asymmetry, on a members individual creativity. Considering that the main stream of conflict asymmetry research rarely focused on people at different levels of hierarchical relationships, the present study addressed this limitation by examining the leader-member conflict asymmetry in one-to-multi vertical dyads. Data from 50 leader-member dyads tested our multilevel hypotheses, which showed that leader-member conflict asymmetry (i.e., the member conflict scale subtracted from the leader conflict scale) negatively relates to a members proactive creativity, but positively relates to members responsive creativity. The leaders higher perception of conflict decreased the proactive creativity of members but increased their responsive creativity. A members psychological safety fully mediated the relationship between the leader-member conflict asymmetry and the members proactive creativity.I. INTRODUCTION 1 II. THEORY AND HYPOTHESIS 5 1. Leader-Member Conflict Asymmetry 5 1.1 Leader: the higher perceiver of conflict 5 1.2 Member: the higher perceiver of conflict 7 2. Mediating factors 8 2.1 Psychological Safety 10 2.2 Intrinsic/Extrinsic motivation 13 III. METHODS 16 1. Sample and procedures 16 2. Measures 17 IV. RESULTS 19 1. Leader-member conflict asymmetry and members creativity 20 2. Mediating effects of psychological safety and intrinsic/extrinsic motivation 21 V. SUPPLEMENTARY ANALYSIS 22 1. Multivariate polynomial regression analysis 22 2. Actual conflict and perceived conflict asymmetries 24 3. Task conflict and relationship conflict asymmetries 25 4. Motivation: mediator or moderator 27 5. Pure effects of leader-member conflict asymmetrydepending on its magnitude 28 VI. DISCUSSION 29 1. Implications 31 2. Limitations and future research 32 REFERENCES 34 ABSTRACT IN KOREAN 55Maste

2014년 인구보건조사(DHS)를 활용한 다수준 분석

학위논문(석사)--서울대학교 대학원 :보건대학원 보건학과(보건정책관리학전공),2019. 8. 김선영.모성사망은 세계적으로 여전히 심각한 보건 문제 중 하나이다. 이는 대부분의 사망이 예방 가능하다는 점에서, 또한 전체 모성사망의 99%가 개발도상국에서 발생하고 있다는 점에서 더욱 주목해야 할 측면이 존재한다. 산전관리(antenatal care, ANC), 산후관리(postnatal care, PNC) 등의 기초적인 모성 관리 서비스가 전반적인 모성건강 개선에 효과적으로 기여할 수 있다는 것은 과거 많은 연구에서 입증되었다. 그러나 여전히 개발도상국 등지에서는 서비스 이용에 지연을 일으키는 여러 차원의 장애물들로 인해 산모의 서비스 추구 수준이 낮은 상황에 머물러 있다. 본 연구의 대상지인 가나와 케냐는 전체 모성사망 부담의 상당 부분(66%)을 차지하는 사하라 이남 아프리카 지역 내 위치한다. 두 국가 모두 저중소득국(lower middle income country)에 속하며 국가 소득수준(GNI per capita) 또한 유사하나, 두 국가의 모성사망비 (maternal mortality ratio)에는 유의한 차이가 나타나고 있다. 이러한 측면에서 본 연구는 가나와 케냐 여성의 모성건강 서비스 이용에 영향을 미치는 요인이 무엇인지와, 각국 영향 요인의 양상이 어떻게 다른지 살펴봄으로써 국가간 비교 연구를 실시하고자 하였다. 분석을 위한 원자료는 2014년 가나 및 케냐 인구보건조사(Demographic and Health Survey, DHS)의 여성 설문지 자료를 활용하였다. 연구의 결과변수는 ANC, 시설 출산 및 PNC의 이용 수준을 통합적으로 고려한 모성 건강관리 추구 행위(maternal health care seeking behavior, MSB)로서, 이는 총 4개 수준 – lowest, mid-low, mid-high, highest – 으로 구성된 순서형 변수이다. 연구 대상자는 최근 5년 내 출산 경험이 있는 가나 및 케냐 내 15-49세 여성 총 5,484명(가중치 적용 시 총 5,144명)이며, 앤더슨 행동 모형을 기반으로 연구의 개념 틀을 작성하였다. 자료 분석의 경우 먼저 기술분석을 통해 가나와 케냐 내 전체적인 MSB 분포 및 연구 대상자의 특성을 확인하였으며, 이와 함께 카이제곱 검정을 실시하여 MSB와 각 예측변수 간의 연관성을 살펴보았다. 이후 두 국가 MSB의 영향 요인을 분석하는데 있어 DHS 자료의 위계적 특성 및 결과변수의 순위적 속성을 고려하여 다수준 순서형 로지스틱 회귀(multilevel ordinal logistic regression) 분석을 수행하였다. 이를 통해 개인 수준의 MSB를 설명함에 있어 커뮤니티의 영향을 함께 살펴보고자 하였다. 분석 결과, 전체 가나 여성 중 highest에 속한 비율이 약 65%, 케냐의 경우 그 비율이 약 31%로 나타나 전반적으로 가나의 MSB 수준이 케냐보다 높은 편으로 나타났다. 다수준 분석 시 총 4개 모형을 적합하였으며, 가장 먼저 영모형(null model)의 적합을 통해 급내상관계수(intraclass correlation coefficient)를 산출, 다수준 분석 방법의 적합성을 확인하였다. 또한 가나와 케냐 각각의 4개 모형 모두에서 집단간 분산이 통계적으로 유의하여, 커뮤니티 특성이 개인 수준의 MSB에 영향을 끼친다는 것을 검증할 수 있었다. 개인 및 커뮤니티 수준의 변수를 모두 투입한 Model 4 분석 결과, 가나와 케냐 여성의 MSB에 공통적으로 영향을 미치는 요인은 여성의 교육수준, 가정의 경제수준, 임신에 대한 욕구, 커뮤니티 빈곤 수준 및 행정구역이었다. 이 외 가나의 경우 종교, 건강보험 가입 여부 및 의료 서비스 접근에 대한 어려움이, 케냐의 경우 연령, 인종, 배우자/파트너의 교육수준, 미디어에 대한 접근, 피임 여부 및 거주지역이 MSB와 유의한 연관성을 지닌 요인으로 확인되었다. 가나는 비교적 우호적인 정책 환경과 여러 이니셔티브의 성과로 다소 높은 수준의 MSB를 보이고 있다. 이에 반해 케냐는 전반적으로 여성의 모성 서비스 이용이 낮은 수준에 머물러 있다. 본 연구 결과로 미루어 보아 두 국가 모두 교육 시스템의 강화 및 질 제고, 국가 전체의 균형 발전을 위해 노력하는 동시에 커뮤니티 기반의 소득창출, 현금지원 사업 등을 통해 소외계층 여성을 별도로 지원함이 필요하다. 또한 지역간 건강 불평등이 나타나는 원인을 심층 분석함으로써 각 지역의 맥락에 따라 모성건강 사업의 확대를 위한 타당한 전략을 수립해야 할 것으로 보인다. 한편, 가나의 경우 토속신앙에 근거한 잘못된 보건 지식 및 실천을 바로잡기 위한 커뮤니티 차원의 건강증진 교육, 빈곤층에 대한 건강보험 지원 강화 및 급여체계 개선, 지리적으로 접근이 어려운 마을 대상의 가정 방문 및 사회동원 캠페인 등의 전략을 고려해볼 수 있다. 한편, 케냐의 경우 인종 간 문화적 차이를 민감하게 반영한 보건 교육이 제공되어야 할 필요가 있으며, 보다 많은 주민들에게 주요 건강 메시지를 효과적으로 전달할 수 있도록 각종 미디어를 활용하는 전략을 수립함과 함께 국가 전반에 걸쳐 미디어 접근 향상을 위한 통신 인프라 개선 사업을 추진해야 할 것이다. 이와 같은 정책적 함의를 제공함과 함께, 본 연구는 가나 및 케냐 여성의 모성건강 서비스 이용에 영향을 미치는 요인을 분석함에 있어 커뮤니티의 영향을 중요하게 고려하여 이의 영향을 밝혀냈고, 여성의 산전, 출산 및 산후기의 모성 서비스 이용을 MSB라는 단일변수 내 동시에 고려하여 이의 결정 요인을 통합적으로 제시하였다는 점에서 그 의의를 찾을 수 있다.Background: It is quite evident that most of maternal deaths occur in lower- and middle-income countries, where the level of maternal health care utilization remains much lower than high income countries. In addition to this disparity by income, significant differences in womens health status are being observed between regions. In 2015, 66% of all maternal deaths took place within Sub-Saharan Africa (SSA) alone. However, previous literatures have iteratively emphasized that the great majority of maternal deaths could have been averted if essential maternal care were provided in a timely manner. Above all, antenatal care (ANC), delivery care (DC), and postnatal care (PNC) turned out to be most effective in preventing urgent complications during prenatal, delivery and postpartum periods. Our study setting, Ghana and Kenya, are located in SSA region and regarded as a lower middle-income country, while their level of maternal mortality does not exhibit similar levels. For this reason, this study aims to explore factors associated with maternal health care utilization in Ghana and Kenya, focusing on the influences of communities. Methods: We utilized data acquired from Demographic and Health Survey (DHS) conducted in 2014. Study population includes a total of 5,484 women (5,144 women if weights applied) aged 15-49 years who had at least one birth in past five years. Outcome variable, named as maternal health care seeking behavior (MSB) was adapted from the prior research and composed of four levels – lowest, mid-low, mid-high and highest – by considering the level of utilization of ANC, DC and PNC in a comprehensive way. We developed the conceptual framework of the study based on Andersens behavioral model. Multilevel ordinal logistic regression was performed through Stata SE 15.0 software to address the study objective. Results: Overall, about 65% of Ghanaian women belonged to the highest level of MSB, compared to 31% in Kenya. This indicates that the level of utilization of maternal health care is relatively higher in Ghana. Through the multilevel analysis employed in this study, we could examine the impact of community characteristics on the individual-level MSB as originally intended. When women had a secondary level of education, the higher wealth index and desire for pregnancy, and the lower the community poverty level, the odds of being beyond a particular category of MSB increased for both countries. Furthermore, an unequal distribution of MSB level was identified among administrative divisions. Along with these factors, religion, health insurance coverage and difficulty in accessing health care were significantly associated with MSB for Ghanaian women. On the other hand, mothers age, ethnicity, husband/partners educational attainment, access to media, use of contraceptives and place of residence tended to increase or decrease the odds of practicing a higher level of MSB in Kenya. Conclusion: Findings of this study clearly show that there is a need to strengthen the overall educational system and health infrastructure as well as pursue a more balanced socioeconomic development in both countries. At the same time, income generation and cash transfer programs could be designed and implemented for the less privileged women. It might be mutually crucial for the central and local governments to analyze what directly and indirectly causes maternal health disparities within each country and develop relevant policies on the basis of evidence collected. In Ghana, health education to correct womens wrong perceptions, NHIS strengthening to support more poor women and home visits or social mobilization campaigns to reach mothers in underserved areas could be executed in order to promote maternal health utilization. For Kenyan women, we recommend that future health initiatives might consider developing more culturally sensitive materials reflecting each ethnic groups traditions for health promotion and taking advantage of mass-media to convey key information on maternal health to the general public, along with the improvement of communications infrastructure at the national scale.1. 서론 1 1. 1. 연구의 배경 및 필요성 1 1. 2. 연구목적 6 2. 선행연구 고찰 7 2. 1. 모성사망과 이환 7 2. 2. 모성건강 서비스 이용 요인 10 2. 3. 가나의 보건 현황 13 2. 4. 케냐의 보건 현황 19 3. 연구방법 26 3. 1. 연구자료 26 3. 2. 연구대상 28 3. 3. 연구모형 29 3. 4. 변수의 정의 32 (1) 종속변수 32 (2) 설명변수 35 (3) 분석방법 43 (4) 윤리적 고려 45 4. 연구결과 46 4. 1. 전체 MSB 수준 분포 46 (1) 가나 DHS 분석 결과 46 (2) 케냐 DHS 분석 결과 46 4. 2. 기술분석 및 카이제곱 분석 결과 48 (1) 가나 DHS 분석 결과 48 (2) 케냐 DHS 분석 결과 54 4. 3. 다수준 분석 결과 60 (1) 가나 DHS 분석 결과 60 (2) 케냐 DHS 분석 결과 67 5. 토의 및 결론 74 5. 1. 연구결과 요약 및 함의 74 5. 2. 연구의 한계 및 제언 83 참고문헌 85 부 록 98 Abstract 112Maste

Posttransplant Lymphoproliferative Disorders in Kidney Transplant Patients: Report from a Single-center over 25 Years

Background: Posttranplant lymphoproliferative disorder (PTLD) is a fatal complication of organ transplantation and standard treatment is either ineffective or too toxic to tolerate. This study aims to evaluate the characteristics of PTLD patients retrospectively. Methods: We enrolled 2,630 kidney recipients who underwent transplantation from April 1979 to June 2007. And we retrospectively reviewed clinical manifestations of PTLD. Results: Among one hundred ninety post-transplant malignancies from 2,630 renal recipients, 11 PTLD were diagnosed during 195.3±11.5 months (0∼388 months) of mean follow up duration. PTLD predominantly occurred in male (Male : Female=10 : 1) and mean age of PTLD patients at the time of PTLD diagnosis was 51±15 year (18∼71 year). Mean time interval to PTLD diagnosis were 126.6±74.8 months (6∼240 months). In aspect of WHO classification, there were no early lesion, 1 polymorphic PTLD (9.1%), 10 monomorphic PTLD (90.9%) and no other types. In aspect of involved organ, GI tract was involved in 1 case, lung in 2 cases, bone in 2 cases, spleen in 2 cases, neck node in 2 cases, liver in 1 case, and multiple organs in 1 case. Conclusions: Our findings showed that the prevalence of PTLD was 0.46%, which was less than reports from Western countries. We also found that the late onset PTLD was more than early onset one, which was another difference from previous reports.ope

서울시 아파트를 대상으로

학위논문 (석사)-- 서울대학교 환경대학원 : 환경대학원 환경계획학과(도시및지역계획전공), 2015. 8. 최막중.오늘날 세계의 도시는 넘쳐나는 자가용으로 인해 교통 혼잡, 대기오염, 소음, 이상화탄소 발생 및 에너지소비 등 사회·경제 및 환경에 걸쳐 다양한 문제를 안고 있으며 1970년대부터 지속적으로 이어져온 자가용의 증가는 더 많은 차량과 도로확장을 부추겨 도시를 확신시키고 있다. 이러한 교통문제를 해결하기 위해 도시 내 자동차의 이용을 감소시키고, 대중교통의 이용을 증가시키는 효율적인 도시개발 및 교통체계를 필요로 한다. 이에 본 연구는 보다 효율적이며 지속가능한 도시개발 및 교통체계에 대한 대안을 제시하기 위해 상대적으로 짧은 기간 동안 집약적인 토지 이용을 바탕으로 세계적 수준의 지하철을 구축한 서울시의 고밀도도시개발이 서울시 지하철 이용자 수에 미치는 영향에 대한 실증 분석을 하였다. 연구의 결과의 요약은 다음과 같다. 첫째, 서울시는 주거개발밀도를 각종 개발 및 정비 사업으로 통해 관리해왔으며, 2010년을 기준으로 서울시의 전체 주거유형 중 아파트가 차지하는 비율이 약 60%로 고밀도주거유형인 아파트를 꾸준히 보급해 오고 있다. 둘째, 서울시 대중교통 분담률은 1990년대부터 60%를 유지해왔고, 그 중 지하철의 분담률은 2010년 기준으로 36%를 차지하면서 서울시의 대표적인 대중교통으로 자리 잡았다. 셋째, 2014년 현존하는 아파트의 평균준공연도와 서울시 지하철 215개 역세권의 준공년도를 바탕으로 지하철 역세권의 개발 패턴을 분석한 결과, 전체 역세권 중 약 80%의 TOD 개발 방식으로 나타났으며, 이는 서울시 도시개발이 지하철 준공이 이루어진 후 아파트가 개발되는 TOD 방식으로 이루지고 있음을 유추할 수 있다. 넷째, 다중회귀 분석 결과, 개발밀도의 지표로 사용된 서울시의 세대 수 밀도가 증가할수록 지하철의 이용자 수가 증가하였고, 지하철 환승과 연계된 버스의 경우 버스의 특성에 따라 보완 혹은 대체관계인 것으로 나타났다. 이상의 분석결과들을 통해 서울시는 대중교통을 위주로 개발이 이루어지는 TOD 방식으로 도시개발이 이루어지고 있으며, 이를 바탕으로 고밀도주거지를 역세권에 배치하여 대중교통 수요를 충족 시켰을 것으로 예상된다. 이를 통해 효율적인 대중교통의 이용이 이루어지기 위해서는 역세권을 위주로 고밀 주거지를 배치하는 것이 효율적임을 확인하고, 이는 더 나아가 수평적 형태로 개발되어 대중교통의 입지 선정이 어려운 개발도상국에 보다 효율적인 도시개발 및 교통체계의 본보기로 제시할 수 있을 것이다.Ⅰ. 서론 1 1. 연구의 배경 및 목적 1 2. 연구의 범위 및 방법 2 1) 연구의 범위 2 2) 연구의 방법 및 흐름도 3 Ⅱ. 이론 및 선행 연구 고찰 5 1. 입지이론 5 2. 도시개발밀도와 대중교통 6 1) 대중교통지향개발(TOD)과 개발지향 대중교통(DOT) 6 2) 대량고속수송 시스템의 보급 7 3. 선행연구 9 Ⅲ. 서울시 주거개발밀도 및 대중교통 12 1. 서울시 주거개발밀도 및 대중교통 이용 변화 12 1) 도시개발에 따른 대중교통의 변화 및 지하철 건설 12 2) 주거개발밀도의 변화 13 2. 서울시 아파트 및 지하철 보급 및 도시개발 패턴 14 1) 서울시 아파트 및 지하철 보급현황 14 2) 서울시 지하철 역세권 도시개발 패턴 분석 20 3. 소결 22 Ⅳ. 실증분석 23 1. 주요 변수 및 자료의 구축 23 1) 주거개발밀도 및 지하철 이용자 산정 23 2) 역세권 반경 내/외 주거개발밀도 차 비교분석 28 3) 주거중심 역세권 분류 32 4) 변수의 구성 34 2. 실증분석 37 1) 기술통계 분석 37 2) 다중회귀 분석 39 Ⅴ. 결론 44 1. 연구의 요약 44 2. 연구의 한계 및 시사점 45 ■ 참고문헌 46Maste

형질전환복제돼지 생산을 위한 piggyBac transposon system의 적용

학위논문 (박사)-- 서울대학교 대학원 : 수의학과, 2017. 2. 이병천.PiggyBac transposon has been widely employed to generation transgenic animals using a "cut and paste" mechanism that is occurred by piggyBac transposase recognizing transposon-specific inverted terminal repeat sequences (ITRs) located on both ends of targeted gene. The targeted gene is cut, and then transferred in to TTAA chromosomal sites. In this study, to investigate whether this system can be applied to transgenic cell line establishment, generation of cloned embryos by somatic cell nuclear transfer (SCNT) and also trial of re-differentiation of cell that was generated by transcription factor for donor in producing transgenic pig SCNT cloned embryos. Firstly, to verify the application of piggyBac transposon to establish transgenic cell line and generate its cloned embryos by SCNT, a report gene, RFP (DsRed2), inducible expression vector was constructed using piggyBac transposon system, it was transferred to porcine fetal fibroblast, after enrichment, the transgenic cell line was established. Homogenously RFP expression was well controlled according the fact of existence or nonexistence of doxycycline in established cell line. Also cloned embryos were shown homogenous expression pattern of RFP using the cell line for SCNT donor. Furthermore the cloned embryos were shown normal development without damage by piggyBac transposon system. Octamer-binding transcription factor 4 (Oct4) is a critical molecule for the self-renewal and pluripotency in undifferentiated cell lines like as embryonic stem cell. For investigate the effect of Oct4-overexpression on cell proliferation and development of cloned embryos, Oct4 was firstly transferred to porcine fibroblasts before the introduction of 4 transcription factors in further. Oct4 expression was validated by the immunostaining of Oct4. Cell morphology was changed to sharp, and both proliferation and migration abilities were enhanced in Oct4-overexpressed cells and p16, Bcl2 and Myc were also upregulated. SCNT was performed using Oct4-overexpressed cells, and the development of Oct4 embryos was compared to that of wild-type cloned embryos. The cleavage and blastocyst formation rates were significantly improved in the Oct4 embryos. Interestingly, blastocyst formation of the Oct4 embryos was observed as early as Day 5 in culture, while blastocysts were observed from Day 6 in wild-type cloned embryos. For validating the availability of piggyBac transposon application to generate porcine induced pluripotent cells, coding domain region of porcine Oct4, Sox2, c-Myc and Klf4 from pig ovarian cDNA by PCR was cloned, constructed to piggyBac expression vector, which is inducible expressed by doxycycline and transduced to porcine fetal fibroblast. After 24h transfection, 2 µg/ml doxycycline was added in DMEM/F12 culture media contained 15% FBS, 10ng/ml bFGF and transfected cells were cultured for 2 weeks more. From about 10 days after, outgrowing colonies were formed, picked, digested to single cell and cultured on CF1 feeder cells treated with mitomycin C. They are routinely single cell passaged 1:4~6 at every 2-3 day by enzyme. We verified the colony formation from single cell culture and maintained the colonies up to passage (> 37th). To compare the developmental efficiency of differentiated cells and established cell lines. SCNT was carried out using two types of cells as followed to our previous established protocol. In the results, the cleavage rate and blastocyst formation rate were not shown any significant differences. But total cell number of blastocyst that one of parameter evaluating of quality of embryos was shown significantly increased in established cell lines group. In conclusion, piggyBac transposon system could be applied to establish the transgenic cell lines and cloned embryos for producing of transgenic pig, also it could be used to generated illimitable self-renewal cell line and produce the its cloned embryos. As this gene delivery system will be valuably used in gene modification availability and stability or safety of generating pig models for human biomedical research.GENERAL INTRODUCTION 1 1. Literature review 2 2. General objective 32 GENERAL METHODOLOGY 33 1. Chemicals and materials 34 2. Vector construction 34 3. General cell culture 38 4. Preparation of somatic cell nuclear transfer in pig 39 5. Statistical analysis 41 INTRODUCING TRANSPOSON SYSTEM IN PORCINE CELL 43 Chapter I. Confirmation of piggyBac transposon system to generate transgenic cell line and cloned embryos in pig 44 1. Introduction 44 2. Materials and methods 46 3. Results 48 4. Discussion 52 Chapter Ⅱ. The Key factor of pluripotency, Oct4 enhance proliferation of porcine fibroblasts and development of cloned embryos 54 1. Introduction 54 2. Materials and methods 56 3. Results 60 4. Discussion 69 Chapter Ⅲ. Establishment of transgenic cell line with 4 transcriptional factors using piggyBac transposon and evaluation of development the SCNT cloned embryos. 72 1. Introduction 72 2. Materials and methods 76 3. Results 82 4. Discussion 92 FINAL CONCLUSION 96 REFERENCES 98 국문초록 122Docto

동시조절 유전적 상호작용 발굴을 위한 하이퍼그래프 모델

학위논문 (박사)-- 서울대학교 대학원 : 협동과정 생물정보학전공, 2014. 2. 장병탁.A comprehensive understanding of biological systems requires the analysis of higher-order interactions among many genomic factors. Various genomic factors cooperate to affect biological processes including cancer occurrence, progression and metastasis. However, the complexity of genomic interactions presents a major barrier to identifying their co-regulatory roles and functional effects. Thus, this dissertation addresses the problem of analyzing complex relationships among many genomic factors in biological processes including cancers. We propose a hypergraph approach for modeling, learning and extracting: explicitly modeling higher-order genomic interactions, efficiently learning based on evolutionary methods, and effectively extracting biological knowledge from the model. A hypergraph model is a higher-order graphical model explicitly representing complex relationships among many variables from high-dimensional data. This property allows the proposed model to be suitable for the analysis of biological and medical phenomena characterizing higher-order interactions between various genomic factors. This dissertation proposes the advanced hypergraph-based models in terms of the learning methods and the model structures to analyze large-scale biological data focusing on identifying co-regulatory genomic interactions on a genome-wide level. We introduce an evolutionary approach based on information-theoretic criteria into the learning mechanisms for efficiently searching a huge problem space reflecting higher-order interactions between factors. This evolutionary learning is explained from the perspective of a sequential Bayesian sampling framework. Also, a hierarchy is introduced into the hypergraph model for modeling hierarchical genomic relationships. This hierarchical structure allows the hypergraph model to explicitly represent gene regulatory circuits as functional blocks or groups across the level of epigenetic, transcriptional, and post-transcriptional regulation. Moreover, the proposed graph-analyzing method is able to grasp the global structures of biological systems such as genomic modules and regulatory networks by analyzing the learned model structures. The proposed model is applied to analyzing cancer genomics considered as a major topic in current biology and medicine. We show that the performance of our model competes with or outperforms state-of-the-art models on multiple cancer genomic data. Furthermore, the propose model is capable of discovering new or hidden patterns as candidates of potential gene regulatory circuits such as gene modules, miRNA-mRNA networks, and multiple genomic interactions, associated with the specific cancer. The results of these analysis can provide several crucial evidences that can pave the way for identifying unknown functions in the cancer system. The proposed hypergraph model will contribute to elucidating core regulatory mechanisms and to comprehensive understanding of biological processes including cancers.Abstract . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .i 1 Introduction 1.1 Background and Motivation . . . . . . . . . . . . . . . . . . . . . . . . 1 1.2 Problems to be Addressed . . . . . . . . . . . . . . . . . . . . . . . . . 3 1.3 The Proposed Approach and its Contribution . . . . . . . . . . . . . . 4 1.4 Organization of the Dissertation . . . . . . . . . . . . . . . . . . . . . 6 2 Related Work 2.1 Analysis of Co-Regulatory Genomic Interactions from Omics Data . . 9 2.2 Probabilistic Graphical Models for Biological Problems . . . . . . . . 11 2.2.1 Bayesian Networks . . . . . . . . . . . . . . . . . . . . . . . . . 11 2.2.2 Markov Random Fields . . . . . . . . . . . . . . . . . . . . . . 13 2.2.3 Hidden Markov Models . . . . . . . . . . . . . . . . . . . . . . 15 2.3 Higher-order Graphical Models for Biological Problems . . . . . . . . 16 2.3.1 Higher-Order Models . . . . . . . . . . . . . . . . . . . . . . . 16 2.3.2 Hypergraphs . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17 3 Hypergraph Classifiers for Identifying Prognostic Modules in Cancer 3.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22 3.2 Analyzing Gene Modules for Cancer Prognosis Prediction . . . . . . 24 3.3 Hypergraph Classifiers for Identifying Cancer Gene Modules . . . . 26 3.3.1 Hypergraph Classifiers . . . . . . . . . . . . . . . . . . . . . . 26 3.3.2 Bayesian Evolutionary Algorithm . . . . . . . . . . . . . . . . 27 3.3.3 Bayesian Evolutionary Learning for Hypergraph Classifiers . 29 3.4 Predicting Cancer Clinical Outcomes Based on Gene Modules . . . . 34 3.4.1 Data and Experimental Settings . . . . . . . . . . . . . . . . . 34 3.4.2 Prediction Performance . . . . . . . . . . . . . . . . . . . . . . 36 3.4.3 Model Analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . 42 3.4.4 Identification of Prognostic Gene Modules . . . . . . . . . . . 44 3.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 4 Hypergraph-based Models for Constructing Higher-Order miRNA-mRNA Interaction Networks in Cancer 4.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52 4.2 Analyzing Relationships between miRNAs and mRNAs from Heterogeneous Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 55 4.3 Hypergraph-based Models for Identifying miRNA-mRNA Interactions 57 4.3.1 Hypergraph-based Models . . . . . . . . . . . . . . . . . . . . 57 4.3.2 Learning Hypergraph-based Models . . . . . . . . . . . . . . . 61 4.3.3 Building Interaction Networks from Hypergraphs . . . . . . . 64 4.4 Constructing miRNA-mRNA Interaction Networks Based on Higher- Order Relationships . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 66 4.4.1 Data and Experimental Settings . . . . . . . . . . . . . . . . . 66 4.4.2 Classification Performance . . . . . . . . . . . . . . . . . . . . 68 4.4.3 Model Evaluation . . . . . . . . . . . . . . . . . . . . . . . . . . 70 CONTENTS iii 4.4.4 Constructed Higher-Order miRNA-mRNA Interaction Networks in Prostate Cancer . . . . . . . . . . . . . . . . . . . . . 74 4.4.5 Functional Analysis of the Constructed Interaction Networks 78 4.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 85 5 Hierarchical Hypergraphs for Identifying Higher-Order Genomic Interactions in Multilevel Regulation 5.1 Overview . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 88 5.2 Analyzing Epigenetic and Genetic Interactions from Multiple Genomic Data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 91 5.3 Hierarchical Hypergraphs for Identifying Epigenetic and Genetic Interactions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 92 5.3.1 Hierarchical Hypergraphs . . . . . . . . . . . . . . . . . . . . . 92 5.3.2 Learning Hierarchical Hypergraphs . . . . . . . . . . . . . . . 95 5.4 Identifying Higher-Order Genomic Interactions in Multilevel Regulation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 100 5.4.1 Data and Experimental Settings . . . . . . . . . . . . . . . . . 100 5.4.2 Identified Higher-Order miRNA-mRNA Interactions Induced by DNA Methylation in Ovarian Cancer . . . . . . . . . . . . 102 5.5 Summary . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 6 Concluding Remarks 6.1 Summary of the Dissertation . . . . . . . . . . . . . . . . . . . . . . . 107 6.2 Directions for Further Research . . . . . . . . . . . . . . . . . . . . . . 109 Bibliography . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 111 초록 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 132Docto

Development of radical-stable peroxidases based on peroxidase inactivation mechanism

학위논문 (박사)-- 서울대학교 대학원 : 협동과정 바이오엔지니어링전공, 2015. 2. 한지숙.Peroxidases catalyze a variety of oxidative transformations of many aromatic compounds and thus have potential in biosynthesis and other biotechnological applications. However, the usefulness of these versatile enzymes is limited, as the enzyme is quickly inactivated during the oxidation reaction of aromatic compounds. This low stability of peroxidases results in low product yield due to the incomplete reaction and increased production costs. Many researchers have studied this, and three possible pathways for peroxidase inactivation have been proposed: reaction with excess hydrogen peroxide, sorption by polymer product, and reaction with radical intermediates. The first two pathways have been corroborated with extensive evidencehowever, the free radical-mediated mechanism of peroxidase inactivation has not been fully elucidated. Thus, the dominant inactivation mechanism in the oxidation reaction of phenolic compounds must be revealed. An understanding of the molecular mechanism of radical-mediated inactivation is necessary for protein engineering to improve peroxidase stability. Firstly, the dominant mechanism of peroxidase inactivation during phenol oxidation was determined. Two peroxidases, Coprinus cinereus peroxidase (CiP) and horseradish peroxidase isozyme C (HRPC), showed much higher inactivation rates after the simultaneous addition of phenol and hydrogen peroxide. After the oxidation reaction of phenol, the molecular weights of polypeptides originating from the inactivated peroxidases were slightly increased, and a large fraction of heme from the two inactivated peroxidases remained intact. These findings support the hypothesis that the inactivation of peroxidase during the oxidation of phenol occurs by the coupling of phenoxyl radicals with peroxidase polypeptides. Secondly, the radical coupling site of CiP was identified, and the radical stability of CiP was improved by site-directed mutagenesis. The residue F230 of CiP modified with the phenoxyl radical was mutated to amino acids (Ala) that resist radical coupling. The F230A mutant showed the highest stability against the radical attack, retaining 80% of its initial activity, while the wild-type protein was almost completely inactivated. In addition, no structural changes were observed in CiP after radical coupling. Thirdly, HRPC was also engineered to enhance the radical stability. Phenylalanine residues that are vulnerable to modification by phenoxyl radicals were identified and then changed to Ala to prevent radical coupling. The F68A/F142A/F143A/F179A mutant exhibited dramatic enhancement of radical stability, retaining 41% of its initial activity compared to the wild type, which was completely inactivated. Radical coupling did not change the secondary structure or the active site structure of HRPC. Structure and sequence alignment revealed that radical-vulnerable Phe residues were conserved in homologous peroxidases. Fourthly, the radical-stable CiP mutant, F230A, was applied to the major practical applications, such as the removal of phenol, the decolorization of dye, and the synthesis of polymers. As expected, the removal efficiency of phenol and the decolorization efficiency of Reactive Black 5 were increased four- and five-fold, respectively, compared with that of the wild type. In addition, the phenolic polymer having the highest molecular mass (8850 Da) was synthesized by the F230A mutant in a 50% v/v isopropanol-buffer mixture. A novel engineering strategy to eliminate the radical coupling site increased the radical stability of two peroxidases, CiP and HRPC. This implies that phenoxyl radicals covalently bind to critical Phe residues and inactivate peroxidase by blocking substrate access to the active site of the enzyme.ABSTRACT i CONTENTS iv LIST OF TABLES x LIST OF FIGURES xii LIST OF ABBREVIATIONS xv CHAPTER 1 INTRODUCTION 1 1. 1 Research Backgrounds 2 1. 2 Research Objectives 5 CHAPTER 2 LITERATURE SURVEY 9 2. 1 Peroxidase 10 2. 1. 1 Heme peroxidase classification 10 2. 1. 2 Catalytic mechanism of peroxidase 11 2. 1. 3 Horseradish peroxidase (HRP) 14 2. 1. 4 Peroxidase from C. cinereus 16 2. 2 Applications of Peroxidases 18 2. 3 Inactivation Mechanism of Peroxidase 24 2. 3. 1 Inactivation by hydrogen peroxide 24 2. 3. 2 Inactivation by reaction product 28 2. 3. 3 Inactivation by free phenoxyl radical 30 2. 4 Improvement of Peroxidase Stability through Protein Engineering 31 CHAPTER 3 PEROXIDASE INACTIVAION BY COVALENT MODIFICATION WITH PHENOXYL RADICAL DURING PHENOL OXIDATION 36 3. 1 Introduction 37 3. 2 Materials and Methods 40 3. 2. 1 Chemicals and reagents 40 3. 2. 2 Enzymes 40 3. 2. 3 Peroxidase stability 41 3. 2. 4 Peroxidase-catalyzed reactions 42 3. 2. 5 SDS-PAGE 42 3. 2. 6 HPLC analysis 43 3. 3 Results and Discussion 44 3. 3. 1 Inactivation factors for peroxidase during the phenol oxidation reaction 44 3. 3. 2 The modification of peroxidase polypeptide 47 3. 3. 3 Heme destruction of peroxidase 50 3. 4 Conclusion 53 CHAPTER 4 DEVELOPMENT OF THE RADICAL-STABLE COPRINUS CINEREUS PEROXDIASE (CIP) BY BLOCKING THE RADICAL ATTACK 54 4. 1 Introduction 55 4. 2 Materials and Methods 58 4. 2. 1 Peroxidase expression, purification, and activity assay 58 4. 2. 2 Mass spectrometry analysis 58 4. 2. 3 Molecular docking simulation 61 4. 2. 4 Turnover capacity and radical stability 62 4. 2. 5 Kinetic parameters 63 4. 2. 6 Spectroscopic analysis 64 4. 3 Results and Discussion 66 4. 3. 1 Inactivation of CiP during phenol oxidation 66 4. 3. 2 Formation of an inactive adduct between F230 and the phenoxyl radicals 68 4. 3. 3 Improving radical stability by engineering F230 mutants 72 4. 3. 4 Kinetic studies. 81 4. 3. 5 Molecular docking simulation 83 4. 3. 6 Structure of CiP after the phenol modification 85 4. 4 Conclusion 91 CHAPTER 5 ENGINEERING A HORSERADISH PEROXIDASE C STABLE TO RADICAL ATTACKS BY MUTATING MUTIPLE RADICAL COUPLING SITES 92 5. 1 Introduction 93 5. 2 Materials and Methods 96 5. 2. 1 Materials 96 5. 2. 2 Expression of recombinant HRPC 96 5. 2. 3 Refolding of inclusion body and purification 97 5. 2. 4 Peroxidase activity assay 98 5. 2. 5 Mass spectrometry analysis 98 5. 2. 6 Spectroscopic analysis of HRPC 99 5. 2. 7 Turnover capacity and radical stability 100 5. 2. 8 Molecular docking simulation 101 5. 2. 9 Protein modeling of horseradish peroxidase isoenzyme A2 102 5. 3 Results and Discussion 104 5. 3. 1 Inactivation of HRPC during the phenol oxidation 104 5. 3. 2 Peptide modification of HRPC by radical attack 106 5. 3. 3 Effect of radical modification on structure of HRPC 112 5. 3. 4 Improving the radical stability of HRPC by site-directed mutagenesis of multiple Phe residues 116 5. 3. 5 Kinetic characterization of HRPC wild-type and mutants 124 5. 3. 6 Molecular docking simulation of HRPC wild-type and quadruple mutant 127 5. 3. 7 Highly conversed Phe residues in homologous peroxidases 130 5. 4 Conclusion 135 CHAPTER 6 IMPROVED PRACTICAL USEFULNESS OF PEROXIDASE FROM COPRINUS CINEREUS BY MUTIAON OF PHE230 136 6. 1. Introduction 137 6. 2. Materials and Methods 140 6. 2. 1 Materials 140 6. 2. 2. Peroxidase 140 6. 2. 3 Peroxidase stability 141 6. 2. 4 Removal of phenol 141 6. 2. 5 Decolorization of RB5 142 6. 2. 6 Phenol polymerization 143 6. 2. 7. Kinetic studies 144 6. 3. Results and Discussion 145 6. 3. 1. Phenol removal form aqueous solution 145 6. 3. 2. Decolorization of Reactive Black 5 149 6. 3. 3. Enzymatic polymerization of phenol 151 6. 3. 4. Effect of organic solvent on enzyme stability 156 6. 3. 5. Enzyme stability during phenol oxidation in solvent mixtures 159 6. 3. 6. Kinetic study 162 6. 4. Conclusion 165 CHAPTER 7 OVERALL DISCUSSIONS AND RECOMMENDATIONS 166 BIBLIOGRAPHIES 172 ABSTRACT IN KOREAN 193Docto