경제통합에 관한 연구

학위논문(박사)--서울대학교 대학원 :사회과학대학 경제학부,2020. 2. 김소영.This dissertation consists of two chapters that account for the effects of economic integration between countries. Chapter I analyzed the causality between trade intensity and business cycle synchronization, and Chapter II captured the dynamic interdependence of stock returns. Chapter I empirically researched whether the trade intensity, which was measured by value-added, could significantly explain the output comovement. Three types of trade intensities were constructed by using domestic value-added, total domestic value-added, and net returned domestic value-added, respectively. Using these, this dissertation conducted the empirical analyses based on Ordinary and Two Stage Least Squares for 43 countries from all over the world between 2000 and 2014. The main findings are summarized as follows. First, none of the trade intensities significantly explained the business cycle synchronization. Second, two intra-industry trades, which were constructed by the domestic value-added and total domestic value-added, significantly accounted for the output comovement. Third, the net returned domestic value-added was not important from the empirical point of view. In conclusion, the significant value-added trade channel on business cycle synchronization was not the trade intensity, but the intra-industry trade. Chapter II measured whether the degree of interdependence of stock returns between China and Latin America has been changed over time. Based on the Dynamic Conditional Correlation Multivariate Generalized Autoregressive Conditional Heteroskedasticity (DCC-MGARCH) model, this dissertation documented dynamic changes of interdependence between 2003 and 2018. It then identified the relative importance of Chinese stock market on Latin America by comparing it to the interdependences between the United States and Latin America. The main results are as follows. First, the influence of Chinese stock on the Latin American stock market was not large although the economic relation between both regions has been strongly intensified over time. Second, Chile and Peru were more sensitive to the fluctuation of the Chinese stock return. Third, the stock returns of Latin America were heavily interconnected to the United States depite the enhanced economic relation between China and Latin America.본 학위 논문은 국가 간 경제통합의 효과를 설명하는 두 개의 장으로 구성되었다. 1장에서는 무역 집중도와 경기변동 동조화 간 인과관계를 분석하였고, 2장에서는 주식 수익률의 동적 상호의존도를 측정하였다. 1장에서는 부가가치(Value-added)로 구성한 무역 집중도가 경기변동 동조화 현상을 유의미하게 설명하는지 실증적으로 평가하였다. 먼저 국내에서 창출한 부가가치(Domestic value-added), 국내에서 창출한 총 부가가치(Total domestic value-added), 그리고 국내로 되돌아온 순 부가가치(Net returned domestic valueadded)를 사용하여 세 종류의 무역 집중도를 구축하였다. 이후 2000년부터 2014년까지 전 세계 43개국을 대상으로 최소자승법 및 2단계 최소자승법을 통해 실증분석을 실시하였다. 주요 결과는 다음과 같다. 첫째, 세 종류의 무역 집중도 모두 경기변동 동조화 현상을 유의미하게 설명하지 못했다. 둘째, 국내에서 창출한 부가가치 및 국내에서 창출한 총 부가가치로 구성한 산업 내 무역은 경기변동 동조화 현상을 유의미하게 설명하였다. 셋째, 실증분석 관점에서 볼 때 국내로 되돌아온 순 부가가치는 의미가 없었다. 결론적으로, 국가 간 경기변동 동조화 현상을 유의마하게 설명하는 부가가치 무역 경로는 무역 집중도가 아닌, 산업 내 무역이었다. 2장에서는 중국과 중남미 간 주식 수익률의 상호의존도가 시간이 지남에 따라 어떻게 변하였는지 측정하였다. 먼저 동태적 조건부 상관계수 다변량 일반화 자기회귀 조건부 이분산(DCC-MGARCH) 모형을 통해 2003년부터 2018년까지 주식 수익률의 동적 상호의존도를 도출했다. 다음으로 중남미와 미국 간 동적 상호의존도를 통해 중남미에 중국의 주식 시장이 상대적으로 얼마나 중요한지 식별하였다. 주요 결과는 다음과 같다. 첫째, 중국과 중남미 간 경제적 관계가 다방면으로 강화되었음에도 불구하고, 중국과 중남미 간 주식 수익률의 동적 상호의존도는 낮은 수준을 기록했다. 둘째, 중국의 주식 수익률 변동에 가장 민감하게 반응한 국가는 칠레와 페루였다. 셋째, 중국과 중남미의 경제적 관계 발전에도 불구하고, 중남미 주식 수익률은 미국과 크게 연관되어 있었다.1 Reassessing the Causality between Value-added Trade Intensity and Business Cycle Synchronization 8 1.1 Introduction 8 1.2 Literature Review 11 1.3 Data and Construction 15 1.3.1 Business Cycle Synchronization 16 1.3.2 Trade Channel 16 1.3.3 Control Variables 22 1.4 Models and Results 23 1.4.1 OLS Estimates 23 1.4.2 IV Estimates 26 1.5 Concluding Remarks 29 1.6 Appendix 31 1.6.1 Measurement Error in Duval et al. (2016) 31 1.6.2 Decomposed Terms in Gross Exports 32 1.6.3 Industrial Sectors in WIOT 33 2 Dynamic Interdependence of Stock Returns Based on Information Transmission: Evidence from China and Latin America 35 2.1 Introduction 35 2.2 Literature Review 38 2.3 Data and Descriptive Statistics 41 2.4 Methodology 44 2.5 Results 47 2.6 Concluding Remarks 51 2.7 Appendix 52 2.7.1 Economic Relation between CHN and LAC 52 2.7.2 Conditional Variance of Stock Returns of CHN and LAC-6 53 2.7.3 Conditional Variance of Stock Returns of USA and LAC-6 54Docto

Mitochondria-centric bioenergetic characteristics in cancer stem-like cells

Metabolic and genotoxic stresses that arise during tumor progression and anti-cancer treatment, respectively, can impose a selective pressure to promote cancer evolution in the tumor microenvironment. This process ultimately selects for the most fit clones, which generally have a cancer stem cell like phenotype with features of drug resistance, epithelial-mesenchymal transition, invasiveness, and high metastatic potential. From a bioenergetics perspective, these cancer stem-like cells (CSCs) exhibit mitochondria-centric energy metabolism and are capable of opportunistically utilizing available nutrients such as fatty acids to generate ATP and other metabolic substances, providing a selective advantage for their survival in an impermissible environment and metabolic context. Thus, diverse therapeutic strategies are needed to efficiently tackle these CSCs and eliminate their advantage. Here, we review the metabolic and bioenergetic characteristics and vulnerabilities specific to CSCs, which can provide an unprecedented opportunity to curb CSC-driven cancer mortality rates. We particularly focus on the potential of a CSC bioenergetics-targeted strategy as a versatile therapeutic component of treatment modalities applicable to most cancer types. A cancer bioenergetics-targeted strategy can expand the inventory of combinatorial regimens in the current anti-cancer armamentarium.ope

An integrative somatic mutation analysis to identify pathways linked with survival outcomes across 19 cancer types

MOTIVATION: Identification of altered pathways that are clinically relevant across human cancers is a key challenge in cancer genomics. Precise identification and understanding of these altered pathways may provide novel insights into patient stratification, therapeutic strategies and the development of new drugs. However, a challenge remains in accurately identifying pathways altered by somatic mutations across human cancers, due to the diverse mutation spectrum. We developed an innovative approach to integrate somatic mutation data with gene networks and pathways, in order to identify pathways altered by somatic mutations across cancers. RESULTS: We applied our approach to The Cancer Genome Atlas (TCGA) dataset of somatic mutations in 4790 cancer patients with 19 different types of tumors. Our analysis identified cancer-type-specific altered pathways enriched with known cancer-relevant genes and targets of currently available drugs. To investigate the clinical significance of these altered pathways, we performed consensus clustering for patient stratification using member genes in the altered pathways coupled with gene expression datasets from 4870 patients from TCGA, and multiple independent cohorts confirmed that the altered pathways could be used to stratify patients into subgroups with significantly different clinical outcomes. Of particular significance, certain patient subpopulations with poor prognosis were identified because they had specific altered pathways for which there are available targeted therapies. These findings could be used to tailor and intensify therapy in these patients, for whom current therapy is suboptimal. AVAILABILITY AND IMPLEMENTATION: The code is available at: http://www.taehyunlab.org CONTACT: [email protected] or [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.ope

Droplet-based microtumor model to assess cell-ECM interactions and drug resistance of gastric cancer cells

Gastric cancer (GC) is a common aggressive malignant tumor with high incidence and mortality worldwide. GC is classified into intestinal and diffuse types according to the histo-morphological features. Because of distinctly different clinico-pathological features, new cancer therapy strategies and in vitro preclinical models for the two pathological variants of GC is necessary. Since extracellular matrix (ECM) influence the biological behavior of tumor cells, we hypothesized that GC might be more similarly modeled in 3D with matrix rather than in 2D. Herein, we developed a microfluidic-based a three-dimensional (3D) in vitro gastric cancer model, with subsequent drug resistance assay. AGS (intestinal type) and Hs746T (diffuse type) gastric cancer cell lines were encapsulated in collagen beads with high cellular viability. AGS exhibited an aggregation pattern with expansive growth, whereas Hs746T showed single-cell-level infiltration. Importantly, in microtumor models, epithelial-mesenchymal transition (EMT) and metastatic genes were upregulated, whereas E-cadherin was downregulated. Expression of ß-catenin was decreased in drug-resistant cells, and chemosensitivity toward the anticancer drug (5-FU) was observed in microtumors. These results suggest that in vitro microtumor models may represent a biologically relevant platform for studying gastric cancer cell biology and tumorigenesis, and for accelerating the development of novel therapeutic targets.ope

Migration and invasion of drug-resistant lung adenocarcinoma cells are dependent on mitochondrial activity

A small proportion of cancer cells have stem-cell-like properties, are resistant to standard therapy and are associated with a poor prognosis. The metabolism of such drug-resistant cells differs from that of nearby non-resistant cells. In this study, the metabolism of drug-resistant lung adenocarcinoma cells was investigated. The expression of genes associated with oxidative phosphorylation in the mitochondrial membrane was negatively correlated with the prognosis of lung adenocarcinoma. Because the mitochondrial membrane potential (MMP) reflects the functional status of mitochondria and metastasis is the principal cause of death due to cancer, the relationship between MMP and metastasis was evaluated. Cells with a higher MMP exhibited greater migration and invasion than those with a lower MMP. Cells that survived treatment with cisplatin, a standard chemotherapeutic drug for lung adenocarcinoma, exhibited increased MMP and enhanced migration and invasion compared with parental cells. Consistent with these findings, inhibition of mitochondrial activity significantly impeded the migration and invasion of cisplatin-resistant cells. RNA-sequencing analysis indicated that the expression of mitochondrial complex genes was upregulated in cisplatin-resistant cells. These results suggested that drug-resistant cells have a greater MMP and that inhibition of mitochondrial activity could be used to prevent metastasis of drug-resistant lung adenocarcinoma cells.ope

Alternative lengthening of telomeres is mechanistically linked to potential therapeutic vulnerability in the stem-like subtype of gastric cancer

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Synaptotagmin 11 scaffolds MKK7-JNK signaling process to promote stem-like molecular subtype gastric cancer oncogenesis

Background: Identifying biomarkers related to the diagnosis and treatment of gastric cancer (GC) has not made significant progress due to the heterogeneity of tumors. Genes involved in histological classification and genetic correlation studies are essential to develop an appropriate treatment for GC. Methods: In vitro and in vivo lentiviral shRNA library screening was performed. The expression of Synaptotagmin (SYT11) in the tumor tissues of patients with GC was confirmed by performing Immunohistochemistry, and the correlation between the expression level and the patient's survival rate was analyzed. Phospho-kinase array was performed to detect Jun N-terminal kinase (JNK) phosphorylation. SYT11, JNK, and MKK7 complex formation was confirmed by western blot and immunoprecipitation assays. We studied the effects of SYT11 on GC proliferation and metastasis, real-time cell image analysis, adhesion assay, invasion assay, spheroid formation, mouse xenograft assay, and liver metastasis. Results: SYT11 is highly expressed in the stem-like molecular subtype of GC in transcriptome analysis of 527 patients with GC. Moreover, SYT11 is a potential prognostic biomarker for histologically classified diffuse-type GC. SYT11 functions as a scaffold protein, binding both MKK7 and JNK1 signaling molecules that play a role in JNK1 phosphorylation. In turn, JNK activation leads to a signaling cascade resulting in cJun activation and expression of downstream genes angiopoietin-like 2 (ANGPTL2), thrombospondin 4 (THBS4), Vimentin, and junctional adhesion molecule 3 (JAM3), which play a role in epithelial-mesenchymal transition (EMT). SNU484 cells infected with SYT11 shRNA (shSYT11) exhibited reduced spheroid formation, mouse tumor formation, and liver metastasis, suggesting a pro-oncogenic role of SYT11. Furthermore, SYT11-antisense oligonucleotide (ASO) displayed antitumor activity in our mouse xenograft model and was conferred an anti-proliferative effect in SNU484 and MKN1 cells. Conclusion: SYT11 could be a potential therapeutic target as well as a prognostic biomarker in patients with diffuse-type GC, and SYT11-ASO could be used in therapeutic agent development for stem-like molecular subtype diffuse GC.ope

Role of Mitochondria-Cytoskeleton Interactions in the Regulation of Mitochondrial Structure and Function in Cancer Stem Cells

Despite the promise of cancer medicine, major challenges currently confronting the treatment of cancer patients include chemoresistance and recurrence. The existence of subpopulations of cancer cells, known as cancer stem cells (CSCs), contributes to the failure of cancer therapies and is associated with poor clinical outcomes. Of note, one of the recently characterized features of CSCs is augmented mitochondrial function. The cytoskeleton network is essential in regulating mitochondrial morphology and rearrangement, which are inextricably linked to its functions, such as oxidative phosphorylation (OXPHOS). The interaction between the cytoskeleton and mitochondria can enable CSCs to adapt to challenging conditions, such as a lack of energy sources, and to maintain their stemness. Cytoskeleton-mediated mitochondrial trafficking and relocating to the high energy requirement region are crucial steps in epithelial-to-mesenchymal transition (EMT). In addition, the cytoskeleton itself interplays with and blocks the voltage-dependent anion channel (VDAC) to directly regulate bioenergetics. In this review, we describe the regulation of cellular bioenergetics in CSCs, focusing on the cytoskeleton-mediated dynamic control of mitochondrial structure and function.ope

재무성과와 비재무성과를 중심으로

학위논문(석사) -- 서울대학교대학원 : 행정대학원 공기업정책학과, 2022. 8. 박순애.The global trend of innovation is demanding that SMEs, which form the backbone of Korea's economy, be transformed into innovative SMEs that create high added value rather than being managed as subcontractors to large corporations. It has become an essential condition for the existence and prosperity of Today's open market economy has changed to an environment in which no one can guarantee tomorrow's survival without ceaseless pursuit of innovation regardless of the size of the company. The Korean government's policy on SMEs has shifted away from the past protection-oriented support system to discovering and nurturing 'innovative SMEs' that can create new jobs and new growth engines by enhancing competitiveness to respond to changes in the economic environment. thus reaching the present. In order to discover and foster innovative SMEs, the government started with venture businesses under the Act on Special Measures for the Promotion of Venture Businesses in May 1998, followed by technological innovation SMEs(Innobiz) in August 2001 and A certification system for management innovation-type SMEs(Mainbiz) has been introduced and implemented. Therefore, in this study, the effectiveness of the management innovation-type SME certification system by analyzing the effect of management innovation-type SME certification, which is one of the innovative SME certification systems, on business performance in terms of growth potential, profitability, stability, and employment, focusing on financial performance. was to check. If selected as a management innovation-type SME, it can receive various support from the government and financial institutions. It will be higher than the performance’, and for companies that have received management innovation-type small and medium-sized enterprises certification from the Korea Credit Guarantee Fund between 2015 and 2017 and general companies that have not been certified, one year before and one year after certification, The difference in management performance between the two companies 1 year before and 2 years after certification, 1 year before certification and 3 years after certification was analyzed using propensity score matching(PSM) and difference in difference(DID). As a result of verifying whether there is a difference in the management performance between the two companies before and after certification between the management innovation-type SMEs and non-certified general SMEs, the sales growth rate and total asset growth rate are from T+1 to T+3 after certification. was found to have superior management performance. In terms of operating profit ratio on sales (profitability), total asset operating profit ratio (profitability), debt ratio (stability), and interest coverage ratio (stability) overall, management innovation certified companies outperformed non-certified companies, but in terms of growth potential, profitability, Statistical significance gradually decreases in the order of stability, so it is necessary to be careful in interpretation. In the case of non-financial indices, in terms of employment growth rate, management innovation-type certified companies performed inferior to non-certified companies in the T+3 period, and no significant results were calculated in the labor productivity index. However, in the case of some financial indicators, it was confirmed that non-certified SMEs showed better management performance than management innovation-type certified SMEs in a specific certification year, or that management innovation-type certified SMEs showed a negative relationship in terms of employment growth rate. Therefore, it seems necessary to enhance the effectiveness of the management innovation-type SME certification system through analysis of the causes of the decrease in management performance after certification of management innovation-type SMEs and thorough follow-up management of management innovation-type certified companies. Based on the results of this study, it seems that various institutional supplements, including improvement of examination indicators, are needed to select excellent management innovation-type certified companies. In addition, it is judged that it is necessary to strengthen the competency of the examiner to determine whether a management innovation-type certified company is a company that can create long-term performance with excellent innovation capability and will to innovate.전 세계적으로 대세가 된 혁신의 흐름은 우리나라 경제의 중추를 이루고 있는 중소기업이 단순한 대기업의 하청 방식 운영을 넘어서 고부가가치를 창출하는 혁신형 중소기업으로 바뀌기를 요구하고 있으며, 이는 선택이 아니라 기업의 존립과 번영을 위한 필수 조건이 되고 있다. 오늘날 개방된 시장경제에서 기업의 규모와 무관하게 혁신 역량과 혁신 의지가 없는 한 내일의 생존을 장담할 수 없는 환경으로 변화된 것이다. 중소기업에 대한 우리나라 정부의 정책은 과거 보호 중심의 지원방식 에서 탈피하여, 경제환경 변화에 대응할 수 있도록 경쟁력을 제고하여 새로운 일자리와 신성장동력을 창출할 수 있는 ‘혁신형 중소기업’을 발굴·육성하는 방향으로 전환하여 현재에 이르고 있다. 정부는 혁신형 중소기업 발굴 및 육성을 위하여 1998년 5월 ‘벤처기업 육성에 관한 특별조치법’에 따른 벤처기업을 필두로 2001년 8월에는 기술혁신형 중소기업(이노비즈)을, 2006년 7월에는 경영혁신형 중소기업(메인비즈)에 대한 인증제도를 각각 도입하여 시행하고 있다. 본 연구에서는 국내 혁신형 중소기업 인증제도의 하나인 경영혁신형 중소기업 인증이 기업의 성장성, 수익성, 안정성, 고용 측면에서 경영성과에 미치는 영향을 재무성과와 비재무성과로 나누어 분석하여 경영혁신형 중소기업 인증제도의 효과성을 확인하고자 하였다. 경영혁신형 중소기업으로 선정될 경우 정부, 지자체 및 금융기관 등으로부터 다양한 지원을 받을 수 있다. 따라서 경영혁신형 인증을 받은 이후에는 상대적으로 양호한 경영성과를 나타낼 것이라는 가정 하에 ‘경영혁신형 중소기업의 경영성과는 인증을 받지 않은 일반 중소기업의 경영성과보다 높을 것이다’라는 가설을 설정하고, 신용보증기금으로부터 2015년부터 2017년 사이에 경영혁신형 중소기업 인증을 받은 기업과 인증을 받지 않은 기업을 대상으로 인증 1년 전과 인증 1년 후, 인증 1년 전과 인증 2년 후, 인증 1년 전과 인증 3년 후의 양 기업 간 경영성과 차이를 성향점수매칭(PSM)과 이중차감법(DID)을 활용하여 분석하였다. 경영혁신형 중소기업과 경영혁신형 인증을 받지 않은 중소기업 간에 인증 전과 인증 후의 경영성과의 차이가 존재하는지 검증한 결과, 매출액증가율과 총자산증가율은 인증 후 T+1기부터 T+3기까지 인증기업의 경영성과가 우월한 것으로 드러났다. 부채비율(안정성)의 경우 경영혁신형 인증기업이 비인증기업에 비해 경영성과가 좋지 않은 것으로 나타났고, 매출액영업이익률(수익성), 총자산영업이익률(수익성), 이자보상배율(안정성)도 전반적으로 경영혁신형 인증기업이 비인증기업보다 우월한 경영성과를 보여주었다. 다만, 성장성에서 수익성, 안정성 순으로 통계적 유의성이 점차 감소하여 해석에 주의할 필요가 있다. 비재무지표의 경우 고용증가율은 T+3기에서 경영혁신형 인증기업이 비인증기업보다 열위한 성과를 보였고, 노동생산성 지표에서는 관찰기간 동안 유의한 결과값이 산출되지 않았다. 일부 재무지표의 경우 특정 인증연도에서 비인증 중소기업이 경영혁신형 인증 중소기업보다 양호한 경영성과를 나타낸다거나 고용증가율 면에서 경영혁신형 인증기업이 오히려 부(-)의 관계를 보이기도 하는 것을 확인할 수 있었다. 따라서 경영혁신형 중소기업 인증 이후 경영성과가 오히려 감소하는 원인을 분석하고, 경영혁신형 인증기업에 대한 철저한 사후관리를 통해 경영혁신형 중소기업 인증 제도의 유효성을 제고할 필요가 있다고 하겠다. 본 연구결과를 바탕으로 우수한 경영혁신형 인증기업을 선발할 수 있도록 심사지표 개선을 포함한 다양한 제도적 보완이 필요할 것으로 보인다. 또한 경영혁신형 인증기업이 우수한 혁신역량과 혁신의지를 가지고 장기적인 성과를 창출할 수 있는 기업인지 판단할 수 있는 심사자의 역량 강화가 필요할 것으로 판단된다.제1장 서론 1 제1절 연구의 배경 및 목적 1 제2절 연구의 범위 및 방법 3 제2장 이론적 배경 및 선행연구 분석 4 제1절 자원기반관점 4 제2절 경영혁신 6 1. 경영혁신의 개념 6 2. 경영혁신의 성공 요인 8 3. 경영혁신의 성과 9 제3절 경영혁신형 중소기업 인증 10 1. 경영혁신형 중소기업 10 2. 혁신형 기업과 경영성과에 관한 선행연구 17 제3장 연구 설계 22 제1절 연구 절차 23 제2절 연구문제 및 가설 설정 24 1. 연구문제 24 2. 가설 설정 24 제3절 연구의 분석틀과 변수의 정의 26 1. 연구의 분석틀 26 2. 변수의 조작적 정의 28 제4절 자료수집 및 분석방법 31 1. 자료 수집 31 2. 분석 방법 32 제5절 연구의 기대효과 37 제4장 실증분석결과 39 제1절 분석대상자료 및 기술통계 39 1. 분석 대상 및 표본 구성 39 2. 기술통계량 39 제2절 성향점수매칭을 통한 표본 추출 42 제3절 경영혁신형 인증의 효과 분석 47 1. 성장성 지표 47 2. 수익성 지표 50 3. 안정성 지표 53 4. 비재무적 지표 56 5. 분석결과 요약 59 제5장 결론 62 제1절 연구의 요약 62 제2절 시사점 63 제3절 연구의 한계 및 향후 과제 64 참고문헌 66 Abstarct 70석

Machine Learning Predictor of Immune Checkpoint Blockade Response in Gastric Cancer

Predicting responses to immune checkpoint blockade (ICB) lacks official standards despite the discovery of several markers. Expensive drugs and different reactivities for each patient are the main disadvantages of immunotherapy. Gastric cancer is refractory and stem-like in nature and does not respond to immunotherapy. In this study, we aimed to identify a characteristic gene that predicts ICB response in gastric cancer and discover a drug target for non-responders. We built and evaluated a model using four machine learning algorithms for two cohorts of bulk and single-cell RNA seq to predict ICB response in gastric cancer patients. Through the LASSO feature selection, we discovered a marker gene signature that distinguishes responders from non-responders. VCAN, a candidate characteristic gene selected by all four machine learning algorithms, had a significantly high prevalence in non-responders (p = 0.0019) and showed a poor prognosis (p = 0.0014) at high expression values. This is the first study to discover a signature gene for predicting ICB response in gastric cancer by molecular subtype and provides broad insights into the treatment of stem-like immuno-oncology through precision medicine.ope