객담 전사체 분석을 통한 노인 천식의 생물학적 경로 분석

학위논문 (박사)-- 서울대학교 대학원 : 의과대학 의학과, 2019. 2. 조상헌.Background: Elderly asthma (EA) shows characteristics different from those of conventional asthma. EA is increasing but its specific pathogenesis remains unclear. Currently, systems biology is widely used in biological research because of the rapid advancement of high-throughput technologies. This study aimed to identify EA-related biological pathways by analyzing genome-wide gene expression profiles in sputum cells using systems biology techniques. Methods: We analyzed gene expression profiles in induced sputum of EA patients and healthy elderly controls. A total of 3,156 gene probes with significantly different expressions between the two groups were identified. We performed hierarchical clustering of genes to classify EA patients. Gene set enrichment analysis (GSEA) and weighted gene co-expression network analysis (WGCNA) were both performed to provide biological information. We also replicated our results using public gene expression data available from Gene Expression Omnibus. Results: Fifty-five EA patients and ten elderly control subjects were enrolled. Two distinct gene clusters were found. Cluster 1 (n=35) showed a lower eosinophil proportion in sputum and less severe airway obstruction compared to cluster 2 (n=20). The replication data set also identified two gene clusters (Cluster 1` and Cluster 2`). We found five gene sets enriched in cluster 1 and three gene sets enriched in cluster 2. Among these, we confirmed that two gene sets were significantly enriched in the replication data set (OXIDATIVE_PHOSPHORYLATION (OXPHOS) gene set in Cluster 1` and EPITHELIAL_MESENCHYMAL_TRANSITION (EMT) gene set in Cluster 2`). These were also enriched in a subgroup analysis that consisted of individuals who had never smoked. We also found four leading edge genes (MRPS11, HSPA9, NUDF4, and ACTA1) in the OXPHOS gene set and two (SNTB1 and FUCA1) in the EMT gene set. WGCNA revealed four modules in cluster 1 and 18 modules in cluster 2. The brown module of cluster 1 and the magenta module of cluster 2were correlated with FEV1/FVC ratio in EA patients. These two modules were also replicated using the replication data set. Conclusion: The findings of two distinct gene clusters in EA and different biological pathways within each gene cluster suggest two different pathogenic mechanisms underlying EA. We postulate that oxidative stress and cellular senescence-associated with aging may be important in the development or progress of EA, and these could be an important development for effectively treating EA.서론: 노인 천식은 전형적인 천식과는 다른 특징을 가지고 있다. 노인 천식의 유병율은 지속적으로 증가하고 있으나 그 병리 기전은 불분명하다. 본 연구는 객담에서 추출한 유전자 발현을 최근의 새로운 방법론을 이용하여 분석하고 이를 통하여 노인 천식과 관련된 생물학적 경로를 규명하고자 한다. 방법: 노인 천식 환자와 정상 대조군의 유도 객담에서 유전자 발현을 분석하였다. 두 군 간 차별 발현되는 3156개의 유전자 프로브를 확인하고 이를 이용하여 계층 클러스터링을 시행하여 노인 천식 환자를 두 클러스터 (Cluster) 로 구분하였다. Gene set enrichment analysis (GSEA)과 Weighted gene co-expression network analysis (WGCNA)를 통하여 유전자 발현을 분석하였고 노인 천식의 새로운 생물학적 경로를 확인하였다. 또한 Gene Expression Omnibus (GEO) 에 공개된 유전자 정보를 이용하여 이러한 결과를 재확인하였다. 결과: 55명의 노인 천식 환자와 10명의 정상 노인 대조군이 연구에 참여하였다. 클러스터 분석을 통하여 뚜렷한 두개의 군집이 확인되었다. 35명의 환자로 구성된 첫번째 군집 (Cluster 1)은 20명의 환자로 구성된 두번째 군집 (Cluster 2)에 비하여 객담 호산구 분율이 낮고 기도 폐색이 경미한 특징을 보였다. GEO에 공개된 유전자 정보를 이용하여 클러스터 분석을 시행하였을 때 역시 두개의 군집이 확인되었다 (Cluster 1`와 Cluster 2`). GSEA 를 시행하여 Cluster 1에서 5개의 유전자 세트와 Cluster 2에서 3개의 유전자 세트의 발현이 증가하여 있음을 확인하였다. GEO에서 공개된 유전자 정보를 이용하여 같은 방법으로 분석하여 발현이 증가되어 있는 유전자 군집을 확인하였고 이 중 2개의 유전자 세트 [Cluster 1` 에서 OXIDATIVE_PHOSPHORYLATION (OXPHOS), Cluster 2` 에서 EPITHELIAL_MESENCHYMAL_TRANSITION (EMT))가 공통적으로 발현이 증가되어 있음을 확인하였다. 또한 이 두 유전자 세트는 비흡연자들만을 대상으로 분석하였을 때도 발현이 증가되어 있었다. 두개의 유전자 군집을 추가로 분석하였을 때 첫번째 군집의 OXPHOS 유전자 세트에서 4개의 leading edge 유전자 (MRPS11, HSPA9, NUDF4, ACTA1) 와 두번째 군집의 EMT 유전자 세트에서 2개의 leading edge 유전자 (SNTB1, FUCA1)를 확인하였다. WGCNA를 통한 분석에서 첫번째 군집에서 4개, 두번째 군집에서 18개의 모듈을 확인하였고, 첫번째 군집의 갈색 모듈과 두번째 군집의 자홍색 모듈이 노인 천식 환자의 FEV1/FVC 비율과 연관이 있음을 확인하였다. 이 두 모듈은 GEO 자료를 이용한 분석에서도 보존됨을 확인하였다. 결론: 노인 천식 환자의 객담에서 두개의 뚜렷한 유전자 세트가 각 군집에서 발현이 증가되어 있음을 확인하였다. 이는 노인 천식의 병리 기전에서 두개의 다른 생물학적 경로가 작용함을 시사하는 소견이라 할 수 있겠다. 이는 노인 천식의 발생과 진행에서 중요한 경로로 보이며 향후 노인 천식의 치료에도 중요할 수 있을 것으로 보인다.Abstract (English) ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ i Introduction ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 1 Methods ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 6 Results ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 11 Discussion ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 48 References ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 56 Abstract (Korean) ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ iv List of tables Table 1. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 16 Table 2. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 18 Table 3. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 19 Table 4. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 20 Table 5. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 22 Table 6. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 24 Table 7. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 26 List of Figures Figure 1. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 28 Figure 2. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 29 Figure 3. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 30 Figure 4. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 31 Figure 5. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 33 Figure 6. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 34 Figure 7. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 36 Figure 8. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 37 Figure 9. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 38 Figure 10. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 39 Figure 11. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 41 Figure 12. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 42 Figure 13. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 44 Figure 14. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 45 Figure 15. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 46Docto

건강보험 심사평가원 자료를 통하여 분석한 만성 알레르기질환의 유병율 추이

학위논문 (석사)-- 서울대학교 대학원 : 의학과, 2015. 2. 조상헌.Background: Although the prevalence of chronic allergic diseases has increased worldwide for several decades, some developed countries recently have shown a slowdown in the incidence of allergic diseases. The aim of this study was to evaluate the recent trends in the prevalence of asthma and other chronic allergic diseases in Korea. Methods: From a database of approximately 50 million beneficiaries in the Korean National Health Insurance (NHI) and Health Insurance Review and Assessment Service (HIRA), data-sets of patients with diagnoses of atopic dermatitis, allergic rhinitis, and asthma were extracted. We analyzed the annual prevalence of asthma, allergic rhinitis, and atopic dermatitis in Korea from 2009 to 2013. Results: The prevalence per 1,000 people of atopic dermatitis, allergic rhinitis, and asthma in 2013 was 20.3, 127.3, and 39.4, respectively. When divided into 10-year age groups, the prevalence of all three diseases was highest in the age group under 10. The prevalence of atopic dermatitis and allergic rhinitis had a decreasing pattern with older age, but for asthma, it showed an increasing pattern for the age group 30-39 and another peak for the age group 70-79. During the study period from 2009 to 2013, the prevalence of allergic rhinitis steadily increased in all age groups including the fastest growth in the age group under 10 with an annual average growth rate of 3.2%. In contrast, the prevalence of asthma and atopic dermatitis did not increase during the same period and instead showed a decrease in the age group under 10. Conclusion: We analyzed the prevalence of chronic allergic diseases in Korea based on nationwide health insurance data. While the prevalence of allergic rhinitis increased for the past 5 years, the prevalence of asthma and atopic dermatitis did not show an increase. These results suggest that the prevalence of chronic allergic diseases in Korea might have plateaued currently.Abstract (English) ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ i Introduction ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 1 Methods ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 2 Results ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 4 Discussion ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 13 References ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 18 Abstract (Korean) ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ iv List of tables Table 1. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 7 List of Figures Figure 1. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 8 Figure 2. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 9 Figure 3. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 10 Figure 4. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 11 Figure 5. ∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙∙ 12Maste

분자 동역학 모사를 이용한 나노크기 극미세사의 물성과 안정성 연구

학위논문(석사)--서울대학교 대학원 :기계항공공학부,2003.Maste

3축 여유 자유도 직접 구동 방식 로봇의 동역학 파라미터 추정

학위논문(석사)--서울대학교 대학원 :전기공학부,1999.Maste

분자 동역학을 이용한 고체 평판 위의 나노크기 액적 증발 현상 연구

학위논문(박사) --서울대학교 대학원 :기계항공공학부, 2008.2Docto

전기도금을 통한 간편한 니켈-구리 인화촉매의 제조와 물 산화반응에의 응용

학위논문 (석사)-- 서울대학교 대학원 : 화학생물공학부, 2017. 2. 김재정.Electrochemical water splitting has attracted great attention since it is the most promising strategy for large-scale hydrogen production. Efficient electrolysis is limited due to sluggish kinetics of oxygen evolution reaction (OER), however, as well as high cost of state-of-art precious metals. Hence, numerous researchers endeavored to develop highly active electrocatalyst with low cost. Indebted to this, this study was focused on synthesis of nickel-copper phosphorous electrocatalyst with high OER activity via facile electrodeposition. Optimization of preparation condition confirmed that nickel-copper phosphorous prepared with electrolyte containing 199:1 of Ni2+/Cu2+ ratio exhibited best performance, which even surpasses the OER activity that of NiP, which is already reported as efficient OER catalyst. Suitable Cu addition resulted in lowered Tafel slope and charge transfer resistance compared to NiP. XPS study revealed that Cu addition enhances the role of Ni-P supporting layer, which lies right underneath the OER active, but thermodynamically unstable Ni hydroxide species. Ni spectra showed higher high-valence-state Ni species when Cu was added in the catalyst. The catalyst was electrodeposited with nano-crystalline phase, explained by XRD patterns. According to SEM image, nickel-copper phosphorous has film-like morphology, with uniform element distribution throughout the surface. The catalyst showed excellent robustness up to 18 hrs of OER operation, as well as high Faradaic efficiency over 99%.Chapter 1. Introduction 1 1.1 Hydrogen as a Promising Renewable Energy Source 1 1.2 Electrochemical Water Splitting 5 1.3 Transition-metal-based Catalysts and their Alloys for Water Oxidation 16 1.4 Electrodeposition for Application in OER Electrocatalyst 19 1.5 Purpose of the Study 22 Chapter 2. Experimental 32 2.1 Preparation of Catalyst 32 2.2 Electrochemical Measurements 35 2.3 Gas Chromatography Measurements 37 2.4 Characterization of Catalyst 41 Chapter 3. Results and Discussion 42 3.1 Optimization of Preparation Condition 42 3.2 Optimization of Catalyst Composition 47 3.3 Characterization of Catalyst 55 3.4 Faradaic Efficiency Calculation 72 Chapter 4. Conclusions 75 Bibliography 77 Abstract 80Maste