리 초대수에 관한 고전 W-대수

학위논문(석사) -- 서울대학교대학원 : 자연과학대학 수리과학부, 2021.8. 서의린.In this thesis, we review definitions of classical affine W-algebras and classical finite W-algebras associated to Lie superalgebras and the relation between them. The main purpose of this paper is to provide explicit formulas of free generators of classical finite W-algebras associated to Lie superalgebras. Using these formulas, we are able to calculate Poisson brackets between generators. Also, using free generators of classical affine W-algebras introduced by Suh (2020), we are able to find explicit forms of energy momentum states of classical affine W-algebras.본 학위 논문에서는, 먼저 리 초대수에 관한 고전 아핀 W-대수와 고전 유한 W-대수의 정의를 상기하고 이 둘 사이의 관계를 설명한다. 이 논문의 주 목적은 리 초대수에 관한 고전 유한 W-대수의 생성원들의 구체적인 공식을 제공하는 것이다. 이 생성원들의 공식을 이용하여, 고전 유한 W-대수의 괄호 연산을 계산하는 것이 가능하다. 또한, 최근에 발견된 고전 아핀 W-대수의 구체적인 생성원들을 사용하여, 고전 아핀 W-대수를 일차 분해하게 해주는 에너지 운동량 상태를 찾아 소개할 것이다.1. Introduction 1 2 Poisson vertex algebras 6 2.1 Poisson vertex algebras 6 2.2 Relation between Poisson vertex algebras and Poisson algebras 11 3 Classical affine W-algebras associated to Lie superalgebras 15 3.1 De finition via Drinfeld-Sokolov reduction 15 3.2 De finition via BRST complex 21 3.3 Equivalence between two de finitions 29 4 Structure of classical affine W-algebras 36 4.1 Generators of classical affine W-algebras 36 4.2 Energy momentum states of classical affine W-algebras 39 5 Classical finite W-algebras associated to Lie superalgebras 45 5.1 Relation between classical affine and finite W-algebras 46 5.2 Generators of classical finite W-algebras 48 6 Conclusion 54 Appendix A Vertex algebras 55 A.1 De finition of vertex algebras 55 A.2 Zhu algebra of vertex algebras 58 Appendix B Quantum W-algebras 60 B.1 Quantum affine W-algebras 60 B.2 Quantum fi nite W-algebras 64 Bibliography 68 Abstract (in Korean) 71석

공공기관 고객만족도 조사의 PCSI 2.0 도입에 따른 효과 분석 - 공기업・준정부기관 중심

학위논문 (석사)-- 서울대학교 대학원 : 행정대학원 행정학과, 2018. 2. 김봉환.본 연구에서는 공공기관의 고객만족도 조사 기법인 PCSI(Public-service Customer Satisfaction Index) 2.0의 도입으로 고객만족도의 영향을 알아보고자 실증분석을 실시하였다. PCSI는 공공기관의 특성을 반영한 공공기관 고객만족도 조사모델이다. 2007년에 최초 도입되어 공기업, 준정부기관, 기타 공공기관을 대상으로 매년 1회 기획재정부 주관으로 실시된다. 고객만족도 조사는 대국민 서비스 개선을 통해 공공기관의 고객지향적 마인드 형성에 기여하였으며 관료주의를 개선하는 역할을 했다고 평가된다. 하지만 지속적인 고객만족도 점수의 절대점수 상향화로 신뢰도 저하, 기관별 특수성의 미반영 등 문제점이 제기되었다. 따라서 2015년에 기존 조사모델을 보완한 PCSI 2.0 모델을 개발하여 적용하였다. PCSI 2.0에서는 측정 항목의 정교화, 조사방법 변화, 개인과 법인고객의 구별한 맞춤형 설문, 고객 정의 확대 및 모집단 검증 확대로 조사 방식을 개선하였다. 본 연구에서는 이 신규모델에 대한 효과를 분석하고자 77개 기관(공기업, 준정부기관)의 4개년(2013~2016년) 자료를 수집하였고, 자료를 토대로PCSI 2.0에 대한 효과를 분석하였다. 조사방식의 고도화 및 변경으로 평균 점수가 하락되었고, 기관별 점수의 분포가 넓어졌다. PCSI 2.0 도입 후 고객을 개인과 법인으로 분리하여 고객 유형에 따라 법인 고객이 많을수록 점수가 높아지는 경향을 보였다. 모집단의 검증 강화 등으로 모집단을 확대 하였으나, 모집단은 점수에 영향을 주지 않는다고 분석되었다. 반면 표본산출 방식의 변경으로 표본 크기에 따른 점수에 대한 영향은 적어졌다. 또한 기관의 크기(정원 수)는 클수록 점수가 높아지고, 공기업이 준정부기관보다 점수가 낮다고 분석되었다. 반면 조사방식은 점수에 영향을 미치지 않는다고 분석된다. 고객만족도 조사가 공공기관의 성과평가로서 적용되기 위해서는 공정하고 모든 기관이 수용가능한 조사방법으로 거듭나야할 것이다. 본 연구 결과를 토대로 향후 공공기관 고객만족도가 고객이 아닌 제도적 특성 등에 의한 영향을 최소화하여 전체 기관에 적용할 수 있도록 지수 발전을 위해 발전시켜야 한다. 이를 통해 공공기관과 국민이 모두 수용할 수 있는 방향으로 나아갈 수 있는 계기가 되길 바란다.제 1 장 연구 목적 및 필요성 1 제 2 장 선행연구 및 연구가설 5 제 1 절 고객만족의 선행연구 5 1. 고객 만족의 정의 5 2. 공공 서비스의 고객만족도 조사 개념과 의의 7 3. 해외의 공공서비스 부문 만족도 조사 사례 및 비교 8 제 2 절 PCSI와 PCIS 2.0 모델의 이해 12 1. PCSI 1.0 모델의 이해 12 2. PCSI 2.0 모델의 이해 14 제 3 절 고객만족도 조사의 점수 상승요인 20 제 4 절 연구가설 22 제 3 장 실증분석 31 제 1 절 자료 및 모형 31 1. 조사 대상 자료 31 2. 조사 모형 33 3. 기초통계량 34 제 2 절 실증분석 35 1. 공공기관 고객만족도 점수 t-test 35 2. 공공기관 고객만족도 조사 회귀분석 38 제 4 장 결론 및 정책적 시사점 43 참고문헌 47 부 록 49 Abstract 51Maste

Identification of tumorigenesis related signaling pathways in the tumors with nuclear β-catenin overexpression

의과대학/박사Mutations of β-catenin, CTNNB1, have been reported in various cancers, including colorectal cancer, breast cancer and lung cancer. Most β-catenin mutations are located in exon 3 of β-catenin genes, which lead to stabilization of β-catenin by blocking the destruction complex of β-catenin. In colorectal cancers, APC mutations are detected in 70-80% of colon cancers and β-catenin mutations are mutually exclusive and detected in about 5% of the colorectal cancers. Although the involvement of APC mutations in the altered Wnt/β-catenin pathway activity is well documented, the functional relevance between the deregulated Wnt/β-catenin signaling pathway and β-catenin mutations has not yet been fully understood in colon cancers. Also, the molecular significances of β-catenin mutations in the other cancers are not fully understood. Unlike colorectal carcinomas, nearly all of solid-pseudopapillary neoplasm (SPN) exhibit somatic mutation in exon3 of β-catenin, which results in abnormal nuclear accumulation (overexpression) of β-catenin. Although β-catenin mutation and activation of the Wnt/β-catenin signaling pathway have been implicated in the pathogenesis of SPN, the molecular regulatory networks remain poorly understood. To identify the altered pathways by nuclear overexpression of β-catenin in tumors, colon cancer and SPN were selected as study models. β-catenin mutation is responsible for the development of a small subset of colon cancers, while development of SPN is solely driven by β-catenin mutation. The molecular significances of nuclear β-catenin overexpression were compared in colon cancer as a model of nuclear β-catenin overexpression by altered genes involved in β-catenin degradation, and SPN as a model of nuclear β-catenin overexpression by β-catenin mutation. Since nuclear β-catenin shows heterogeneous expressions in colon cancers, the colorectal tumors were classified by percentage of nuclear β-catenin and identified a subset of colon cancers by comparing gene expression profiles in the colon cancers showing heterogeneous expression of nuclear β-catenin. As a result, it was found that overexpressed nuclear β-catenin activates genes involved in Wnt/β-catenin signaling, Notch signaling, Hedgehog signaling and ECM-receptor interaction in colon cancer. To identify gene subsets associated with nuclear β-catenin overexpression by β-catenin mutation, mRNA expression profiles of SPN and other pancreatic tumors (pancreatic adenocarcinomas and neuroendocrine tumors) were performed. All SPNs harbor β-catenin mutation, while the other pancreatic tumors harbor no β-catenin mutation. Unsupervised clustering analysis of mRNA expression distinguished SPNs as a distinct type of pancreatic tumor. Analysis of differentially expressed genes in SPN demonstrated that genes involved in Wnt/β-catenin, Hedgehog and androgen receptor signaling pathways as well as epithelial-mesenchymal transition were activated in solid-pseudopapillary neoplasms. Finally, the altered expression level of genes involved in three activated signaling pathways was confirmed by using cells transfected with β-catenin constructs. Transfection of mutant β-catenin constructs resulted in the translocation of androgen receptor into the nucleus and up-regulated several molecules involved in Wnt/β-catenin, Notch and Hedgehog signaling. In conclusion, overexpression of nuclear β-catenin commonly or selectively affects the signaling pathways of the Wnt/β-catenin, Notch, Hedgehog and androgen receptor, and contributes to the tumorigenesis of colon cancers and SPN.ope

LEF1; TFE3; and AR are putative diagnostic markers of solid pseudopapillary neoplasms

The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]. We also evaluated the Ki-67 proliferative index to investigate its associations with prognosis. To validate these markers, we studied 91 SPNs as well as 51 pancreatic ductal carcinomas (PDC) and 48 neuroendocrine tumors (NET) as controls. We found frequent and diffuse nuclear expressions of β-catenin (98.9%), AR (81.3%), LEF1 (93.4%), TFE3 (74.7%), FUS (84.6%), and cytoplasmic expression of WIF-1 (96.7%) in SPNs. In contrast, PDCs and NETs showed no expression. (P < 0.001). When beta-catenin, LEF1, and TFE3 staining were combined, the sensitivity and specificity were 100% and 91.9%, respectively. Four (4.4%) SPNs showed distant metastasis and these tumors were associated with a relatively high Ki-67 proliferative index (≥ 5%; P = 0.013). We identified LEF1, TFE3, and AR as putative diagnostic markers of SPN, auxiliary to β-catenin. Incorporated into an immunohistochemical panel, these markers could be beneficial to distinguish SPN from PDC and NET. In addition, we suggest that the Ki-67 proliferative index can be a predictive marker of metastasis in SPNs.ope

Identification of specifically activated angiogenic molecules in HMGB-1-induced angiogenesis

High-mobility group box-1 (HMGB-1) is expressed in almost all cells, and its dysregulated expression correlates with inflammatory diseases, ischemia, and cancer. Some of these conditions accompany HMGB-1-mediated abnormal angiogenesis. Thus far, the mechanism of HMGB-1-induced angiogenesis remains largely unknown. In this study, we performed time-dependent DNA microarray analysis of endothelial cells (ECs) after HMGB-1 or VEGF treatment. The pathway analysis of each gene set upregulated by HMGB-1 or VEGF showed that most HMGB-1-induced angiogenic pathways were also activated by VEGF, although the activation time and gene sets belonging to the pathways differed. In addition, HMGB-1 upregulated some VEGFR signaling-related angiogenic factors including EGR1 and, importantly, novel angiogenic factors, such as ABL2, CEACAM1, KIT, and VIPR1, which are reported to independently promote angiogenesis under physiological and pathological conditions. Our findings suggest that HMGB-1 independently induces angiogenesis by activating HMGB-1-specific angiogenic factors and also functions as an accelerator for VEGF-mediated conventional angiogenesis.ope

Metabolic characteristics of solid pseudopapillary neoplasms of the pancreas: their relationships with high intensity (18)F-FDG PET images

Objective: We aimed to investigate the metabolic characteristics of Solid pseudopapillary neoplasms (SPNs) in relation signal intensities on (18)F-FDG PET scans. Summary Background Data: SPNs of the pancreas commonly show high uptake of 18F-FDG. However, the metabolic characteristics underlying the high (18)F-FDG uptake in SPNs are not well characterized. Materials and Methods: mRNA expressions for glucose metabolism were analyzed in five SPNs, five pancreatic ductal adenocarcinomas (PCAs), and paired normal pancreatic tissues. Among the proteins involved in glucose metabolism, the expressions of five proteins (GLUT1, HK1, PFKM, ENO2, and PKM2) were evaluated in 36 SPNs by immunohistochemistry. Clinical patterns of SPN on PET scans were classified according to the proportion of (18)F-FDG uptake within the whole tumor volume (hot: >/= 70%, mixed: 30 /= 3%) was associated with high SUVmax in pancreatic SPNs (p = 0.002). Conclusions: SPN cells harbor an active molecular capacity for increased glucose metabolism. Especially, defective type SPNs were associated with low metabolic activity and related to low Ki-67 index.ope

Clinicopathologic Features and Molecular Characteristics of Glucose Metabolism Contributing to ¹⁸F-fluorodeoxyglucose Uptake in Gastrointestinal Stromal Tumors

Fluorine-18 fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET/CT) is useful in the preoperative diagnosis of gastrointestinal stromal tumors (GISTs); however, the molecular characteristics of glucose metabolism of GIST are unknown. We evaluated 18F-FDG uptake on preoperative PET/CT of 40 patients and analyzed the expression of glycolytic enzymes in resected GIST tissues by qRT-PCR, western blotting, and immunohistochemistry. Results of receiver operating characteristic curve analysis showed that the maximum standardized uptake value (SUVmax) cut-off value of 4.99 had a sensitivity of 89.5%, specificity was 76.2%, and accuracy of 82.5% for identifying tumors with a high risk of malignancy. We found that 18F-FDG uptake correlated positively with tumor size, risk grade, and expression levels of glucose transporter 1 (GLUT1), hexokinase 1 (HK1), and lactate dehydrogenase A (LDHA). Elevated HK and LDH activity was found in high-risk tumors. Among the isoforms of GLUT and HK, GLUT1 and HK1 expression increased with higher tumor risk grade. In addition, overexpression of glycolytic enzymes M2 isoform of pyruvate kinase (PKM2) and LDHA was observed in GISTs, especially in high-risk tumors. These results suggest that upregulation of GLUT1, HK1, PKM2, and LDHA may play an important role in GIST tumorigenesis and may be useful in the preoperative prediction of malignant potential.ope

β-catenin activation down-regulates cell-cell junction-related genes and induces epithelial-to-mesenchymal transition in colorectal cancers

WNT signaling activation in colorectal cancers (CRCs) occurs through APC inactivation or β-catenin mutations. Both processes promote β-catenin nuclear accumulation, which up-regulates epithelial-to-mesenchymal transition (EMT). We investigated β-catenin localization, transcriptome, and phenotypic differences of HCT116 cells containing a wild-type (HCT116-WT) or mutant β-catenin allele (HCT116-MT), or parental cells with both WT and mutant alleles (HCT116-P). We then analyzed β-catenin expression and associated phenotypes in CRC tissues. Wild-type β-catenin showed membranous localization, whereas mutant showed nuclear localization; both nuclear and non-nuclear localization were observed in HCT116-P. Microarray analysis revealed down-regulation of Claudin-7 and E-cadherin in HCT116-MT vs. HCT116-WT. Claudin-7 was also down-regulated in HCT116-P vs. HCT116-WT without E-cadherin dysregulation. We found that ZEB1 is a critical EMT factor for mutant β-catenin-mediated loss of E-cadherin and Claudin-7 in HCT116-P and HCT116-MT cells. We also demonstrated that E-cadherin binds to both WT and mutant β-catenin, and loss of E-cadherin releases β-catenin from the cell membrane and leads to its degradation. Alteration of Claudin-7, as well as both Claudin-7 and E-cadherin respectively caused tight junction (TJ) impairment in HCT116-P, and dual loss of TJs and adherens junctions (AJs) in HCT116-MT. TJ loss increased cell motility, and subsequent AJ loss further up-regulated that. Immunohistochemistry analysis of 101 CRCs revealed high (14.9%), low (52.5%), and undetectable (32.6%) β-catenin nuclear expression, and high β-catenin nuclear expression was significantly correlated with overall survival of CRC patients (P = 0.009). Our findings suggest that β-catenin activation induces EMT progression by modifying cell-cell junctions, and thereby contributes to CRC aggressiveness.ope

Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype

Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21), this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes; we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.ope

학습조직 구축요인이 직무만족도에 미치는 영향 : 보건의료계 공공조직을 중심으로

학위논문(석사)--서울대학교 보건대학원 :보건학과, 보건정책관리학전공,2006.Maste