Multi-omics analysis based upon immune biomarker PD-L1

학위논문(박사) -- 서울대학교대학원 : 의과대학 협동과정 종양생물학전공, 2023. 8. 구자록.암 진단 및 치료 기법이 발달했음에도 불구하고 폐암은 국내 및 전 세계적으로 높은 발생률과 사망률을 나타내는 질환이다. 최근 도입된 면역항암제는 제한적인 효과와 부작용, 약제 내성을 나타내고 있다. 폐암 발생의 암 화와 악성 기작의 유전적 변이와 신호전달의 분석을 통해 면역 항암에 필요한 폐암의 종양 유전자 표적과 그에 알맞은 신호전달경로의 규명이 필요하다. 폐암 환자 흉수로부터 유래한 세포주 수립한 후에 특성을 분석함으로서 조금 더 임상 치료에 가까운 치료 전략을 제시할 수 있다. 면역 항암 치료의 PD-L1은 종양 표지자로서 그를 기준으로 유전자 바이오마커와 신호전달 경로를 분석, 연구해 보았다. 수립한 세포주들은 환자의 특성을 잘 반영하기에 향후 면역 항암 치료의 표적이 될 수 있는 바이오마커와 신호전달경로를 임상에서 채택하여 적용하게 될 가능성을 제시하고자 한다. 암 환자들의 개인맞춤화치료가 진행되면서 종양의 분자적 발암 경로 및 종양 유전자의 바이오마커와 신호전달경로의 더 깊은 연구가 필요하여 분자적 발암 신호전달 경로, 유전체 분석을 수행하였다. 폐암 환자에서 유래한 세포주 29개를 수립한 후 수립한 세포주의 STR(Short Tandem Repeat) 검사를 통해 환자와 동일한 세포주인 것을 확인한 후 특성분석을 수행하였다. 수립한 세포주를 가지고 유전자의 돌연변이와 각 세포 주에 대한 유전정보의 따른 특징을 규명하여 유전변이와의 상관관계를 밝히고자 하였다. 면역 항암 치료의 진행 여부의 검진방법으로 PD-L1의 발현 정도를 보듯이 우리가 수립한 세포주에서도 주요 분석 결정 분류로 western analysis를 통해 PD-L1 발현 기준으로 세포주를 나누어 분석 시행 하였다. PD-L1의 발현 정도에 따라 나누어진 세포주들은 protein coding 영역인 exome 영역만을 보는 whole exome sequencing (WES), Transcriptome상의 RNA sequencing을 통해 유전 변이와 발현된 유전자들의 발현량의 차이를 확인한 후 PD-L1의 발현 상관관계와 신호전달경로의 상관관계를 밝히고자 하였다. 여러 연구에서 밝혀진 PD-L1의 발현과 EGFR의 돌연변이의 상관관계가 우리가 수립한 세포주에서 같은 경향성을 보여주었고, Protein level과 mRNA level에서의 PD-L1의 상관관계가 있음을 규명할 수 있었다. 또 한, 폐암 환자 흉수 유래로 수립한 29개의 폐암 세포주의 PD-L1의 발현의 차이와 돌연변이의 상관관계가 항암제 내성이나 민감성에서 어떠한 반응성을 보이는지를 연구 분석하여 그와 관련한 기전과 target 하는 메카니즘의 약물 반응성 및 신호전달 경로, 유전자들을 규명할 수 있었다. 항암 약제의 민감성과 유전정보의 분석을 통해 약물의 validation을 할 수 있었으며, 유의미한 결과를 통해 폐암 세포주의 특성을 분석함으로 면역-화학 병용 치료의 면역 항암 요법의 전략 중 하나로 사용될 것으로 사료 된다. 폐암 환자 유래 세포주의 유전체 정보를 가지고 세포생물학적 특성과 면역 치료의 주요 생물 지표인 PD-L1의 발현 상관관계를 파악함으로서 개인의 항암 치료 반응을 예측할 수 있도록 도울 수 있다. 생물 지표인 PD-L1에 따른 분류를 통해 유전자 변이와 약제 감수성의 상관관계를 규명하여 임상적 치료 접근성을 가까이 갈 수 있으며, 이를 통해 유전자 변이와 신호전달 경로가 면역-화학 치료 요법의 유의미한 결과를 도출 가능하다. 항암 치료의 세대가 정밀 종양학에 기인한 개인 맞춤화 되어가고 있듯이 이 연구는 항암 치료의 활용 가능성과 필요성을 보여주는 결과물이 될 것이다.Despite advances in cancer diagnosis and treatment techniques, lung cancer is a disease with high incidence and mortality both domestically and globally. Most of the recently introduced immuno-anticancer drugs show limited effects, side effects, and drug resistance. So, it is crucial to find advanced oncogenic and malignant mechanisms of lung cancer development through analysis of genetic mutations and signal transduction in immune oncology. After establishing 29 cell lines derived from the pleural fluid of lung cancer patients, we suggest clinical treatment strategy by analyzing the characteristics of the patient characteristics. As personalized treatment for cancer patients has progressed, further research on the molecular carcinogenic pathway of tumors and biomarkers and signal transduction pathways of tumor genes was needed. A short tandem repeat (STR) test was confirmed to be the same cell line as the patient, and then characterization study was performed. With the established cell lines, the characteristics of gene mutations and genetic information for each cell line were identified to reveal the correlation with genetic mutations. As expression of PD-L1 is examined as a screening method for the progress of immunotherapy, the established cell lines were analyzed by dividing the cell lines based on PD-L1 expression through western analysis as a major analysis decision classification. The classified cell lines according to the level of expression of PD-L1 were identified to confirm the genetic mutations and the difference in expression level through whole exome sequencing (WES), and RNA sequencing on the transcriptome. This study reveals the correlation between the expression of PD-L1 and the signal transduction pathway. Several previous studies showed the same trend in terms of the correlation between PD-L1 expression and EGFR mutation. This study further supports the correlation between PD-L1 at protein level and mRNA level in established lung cancer cell lines. In addition, it identifies the correlation between PD-L1 expression and genetic mutation, drug sensitivity. `Individual anticancer treatment responses are predicted by identifying the correlation between cell biological characteristics and the expression of PD-L1, which is a key biomarker for immunotherapy. The classification according to the biomarker PD-L1 identifies the relations of genetic variation with drug sensitivity thereby contributing to expanding clinical treatment access and through this, significant results are achieved for immuno-chemotherapy, also contributing to the future cancer therapy. Based upon precision oncology, the generation of anticancer treatment is becoming personalized. This study shows the necessity and potential applications of anticancer treatment in the immunotherapy.Table of Contents Abstract ⅰ Table of Contents ⅳ List of Tables ⅴ List of Figures ⅵ Introduction 1 Materials and Methods 4 Results 13 Discussion 86 References 92 Abstract in Korean 98박

학령전기 보육시설 아동을 위한 한의사 주치의 프로그램 개발 및 평가

학위논문 (석사)-- 서울대학교 보건대학원 : 보건학과(보건정책관리학전공), 2013. 2. 조병희.우리 사회의 여성 경제활동 참여 증가와 정부의 보육시설 확충으로 이른 나이에 장시간 보육시설을 이용하는 아동이 늘어나고 있다. 보육시설은 많은 아동이 밀집해 있어 잦은 접촉으로 인한 감염성 질환의 발생이 용이하며, 면역력이 낮은 영유아의 경우 집단 생활이 체력적, 심리적 스트레스로 작용해 감염성 질환이 지속, 중첩되는 경우가 빈번하다. 아동기의 건강이 일생의 건강을 좌우함에도 불구하고 이들 보육시설 아동에 대한 건강관리 및 중재 프로그램은 미흡한 실정이다. 따라서 본 연구에서는 보육시설 아동들이 흔히 겪는 각종 감염성 질환을 예방하고 건강증진을 도모하기 위하여 전문 의료 인력인 한의사를 보육시설에 주치의로 연계하고, 한의학의 예방적 개념인 養生과 治未病을 바탕으로 관리, 교육, 검진으로 구성된 보육시설 한의사 주치의 프로그램을 개발, 시행하여 그 효과를 평가하였다. 비동등성 대조군 유사실험연구로 서울과 경기도 12곳의 보육시설 아동 총 568명, 보육교사 총 85명을 대상으로 하였으며, 사전설문조사, 프로그램 시행, 사후설문조사의 순으로 12주간 진행되었다. 아동에 대한 프로그램 자체의 효과를 보기 위해 이중차이(Difference in defference, DID)분석 방법을 적용하여 중재 전후의 감염성 질환으로 인한 총 의료이용 일수와 기능적 상태인 총 결석 및 조퇴•지각일수의 변화를 분석하였으며, 결과변수에 영향을 줄 수 있는 다른 설명변수들은 영과잉-음이항-회귀모형을 통해 보정하였다. 보육교사에 대해서는 중재 전후 감염에 대한 태도 변화를 분석하였다. 연구 결과 의료이용 일수는 통계적으로 유의한 차이를 보이지 않았으나 감소한 방향의 결과를 나타내었고(IRR=0.97), 결석 및 조퇴•지각일수는 유의하게 감소하였다(IRR=0.37, p<.05). 두 결과변수에는 공통적으로 아동의 과거질환 여부와 보육시설 이용기간이 유의한 영향을 미치는 것으로 나타났다. 기능적 상태에 있어서는 연령 변수도 유의하였으며, 보육시설의 유형과 규모에 따라서도 유의한 차이를 보였다. 한편, 보육교사의 감염에 대한 태도는 두 군간에 초기 동질성 검정에서 차이가 없었으나, 중재 후에도 유의한 차이를 보이지 않았다. 참여 아동의 학부모들은 프로그램 과정 평가의 일환으로 실시한 프로그램의 유용성과 내용에 대한 만족도 평가에서 프로그램 기간이 짧았다는 응답 외에 모든 문항에서 긍정적인 반응을 보였다. DID 방법을 이용하여 두 집단에 공통적인 추세효과와 시불변변수를 효과적으로 통제한 본 연구 결과에서 보육시설 한의사 주치의 프로그램은 비교적 짧은 중재 기간에도 불구하고 감염성 질환의 예방과 관리에 있어 일부 효과적임을 시사하였다. 따라서 추후 프로그램을 보완하여 일차의료 및 공공보건 영역에서 한의사 주치의와 보육시설 연계를 추진하면 보육시설 아동의 건강증진에 기여할 수 있을 것이다.제 1 장 서론 1 제 1 절 연구의 배경 및 필요성 1 제 2 절 연구목적 3 제 3 절 연구가설 3 제 4 절 개념 정의 3 제 5 절 문헌 고찰 5 제 2 장 연구 방법 12 제 1 절 연구설계 12 제 2 절 연구대상 및 기간 19 제 3 절 연구도구 20 제 4 절 자료수집 및 분석방법 22 제 5 절 연구 윤리 26 제 3 장 연구 결과 27 제 1 절 일반적 특성 및 사전 동질성 검정 27 제 2 절 연구가설 검정 35 제 3 절 프로그램 만족도 평가 39 제 4 장 고찰 41 제 1 절 연구 방법에 대한 고찰 41 제 2 절 프로그램의 효과 평가 46 제 3 절 연구의 제한점 50 제 4 절 연구의 의의 51 제 5 장 결론 및 제언 52 제 1 절 결론 52 제 2 절 제언 52 참고문헌 54 Abstract 74Maste

國家競爭優位向上을 위한 統合적 接近法: 東亞細亞 經濟의 成功要因에 대한 分析 - 韓國의 發展을 中心으로

학위논문 (박사)-- 서울대학교 국제대학원 : 국제학과, 2014. 8. 문휘창.The classical economic theories focus on inherited advantages and their effective utilization when explaining economic development. However, countries that possess advantage show wide discrepancies in their levels of developmentsome have grown rich but others have stayed poor. In order to promote economic and social advancement of less developed countries (LDCs), developed countries and international organizations launched various development activities and programs. Despite these aids, however, their performances vary. This research is dedicated to find the critical factors that caused such different outcomes by mainly focusing on the case of Korea. This dissertation consists of three main parts. In Part I, important economic and business literature on the elements of economic development and success are reviewed, followed by the limitations of the earlier studies. This naturally leads to the need of a new approach for explaining economic development. In Part II, a new approach called the ABCD framework by Hwy-Chang Moon (2012), is presented and a rigorous theoretical support is provided. Later, the validity of this new approach is tested statistically. In Part III, the economic developments of Koreas automobile and film industries are analyzed by using the newly proposed approach, with a special attention to government intervention and industrial policies. Lastly, a summary of the new approach, discussion on the results, and important implications derived from this research are presented. International trade theories, which have the foundations from the work by Adam Smith, assume that a nation has an advantage and should focus on an intensive use of advantageous factors. However, these theories cannot explain two problemsfirst, the different level of economic development of countries with similar natural endowments and second, the development initiatives of a country that does not possess any advantage in factors of production. Productivity theorists emphasized the importance of upgraded labor through education, training, capital investment, and technology progress derived from the best-practice. However, productivity theories cannot fully explain the economic development of LDCs, since good universities, research institutes, or accumulated capitals for upgrading labor, or best-practices are not usually found in LDCs. As commonly known, during the 1960s and 1970s when the newly industrialized countries in Asia, such as Korea, took-off, they did not have these conditions. Another popular approach is on culture. Scholars such as Hofstede (1997), Schein (1998), and Trompenaars (1998) treated culture as a national characteristic which does not easily change. This means the cultural approach cannot explain the difference between ex-ante and ex-post of economic development. Porterian scholars such as Porter (1990) and Moon, Rugman, and Verbeke (1995, 1998) cleverly integrated the important variables determining a nations competitiveness into one model and most other theories represent subsets of Porters comprehensive model. While Porterian approach based on the diamond model brilliantly and systematically classified significant factors of economic development, it cannot explain the underlying force that strengthens or weakens each determinant of the diamond. Based on the empirical studies, Moon (2012) proposed a new framework which explains the fundamental factors that enhance the determinants of economic development. This is called the ABCD framework and consists of four factors: Agility, Benchmarking, Convergence, and Dedication. Agility refers to how fast and accurately a process of business is done and has two sub-factors which are speed and precision. Benchmarking is defined as the search for an industrys best practices that will lead to superior performance. Under this perspective, benchmarking is categorized into two components—imitation and global standard. Convergence is a good mixture of resources and capabilities, and is classified into mixing and synergy-creation. Lastly, dedication means that people work hard and have extra commitment and loyalty for the work. This can is divided into diligence and goal-orientation. In order to prove statistically, this dissertation chooses relevant proxies that can represent each sub-factor and conducts an empirical test with statistical data. Each sub-factor of the ABCD is measured by two criteria, and the values of Cronbachs Alpha for the eight sub-factors are mostly larger than 0.7 except for diligence. This implies that the criteria measure well for each sub-factor, and the consistency is high among other criteria. This study employs two statistical methods: ANOVA and regression. First, ANOVA is utilized to compare the difference between developed and developing countries in terms of four factors of ABCD. Then by using regression, the influences of these factors to economic development are analyzed. All of the four factors show significant difference between developing and developed countries. The dependent variable is GDP per capita, and the independent variables are the ABCD and control variables. The result of the test implies that each ABCD variable explains the difference in GDP per capita among countries. The ABCD frameworks applicability is also demonstrated to explain the development and evolution of two Korean industries: The automobile industry, one of the most important manufacturing industries, and the film industries, a resurging industry as part of the Korean Wave which has been attracting much attention from all over the world to Korea. In 1955, Koreas automobile industry started with a car called Sibal, built on the basis of an abandoned Willys Jeep and other spare parts from the U.S. military. A short time later, Korea started to assemble cars with imported CKD (completely knock-down) kit and to form partnerships with foreign companies. As time passed by, the whole industry changed its function from a simple assembler to automobile developer and the first Korean-developed automobile, Hyundai Pony was produced in 1976. Although Koreas automobile industry faced turmoil during the Asian financial crisis in 1997, Koreas automobile companies were recovered quickly, increased production and exports. According to the International Organization of Motor Vehicle Manufacturers, Korea is the fifth-largest in the world measured by automobile unit production and Hyundai, with its affiliate Kia Motors, is the worlds fifth-biggest auto maker by sales in 2013. Unlike other developing countries, Korean government encouraged to have its own national model car within relatively short time from the beginning of industrialization, despite the nations lack of skills and technology. Under this government effort, partnerships with foreign companies were promoted, although the government prohibited direct investment by foreign companies into Korea. Through CKD kits and partnerships with foreign companies, Korea could learn manufacturing skills and accumulate important technologies. Government aimed to have horizontal integration among manufacturers and auto-parts producers, and these companies formed vertical integration which accelerated car producing capability more effectively. Since Korea did not have enough capital needed for economic development to start with, Korea was motivated with a strong desire for developing its own cars and exporting them to earn foreign hard currency. Unlike the automobile industry that has prospered until today, the Korean film industry enjoyed a golden age between the late 1950s and mid-1960s. In the following two decades, there was a dark age due to interventions by the governments market-distorting policy. As a result, the market share of Korean films decreased unprecedentedly. Especially, their market share in 1993 recorded 15.9%, the lowest ever in the history, after Hollywood production companies began to distribute their films directly into Korea. From the late 1990s, Korea opened its market and changed its view on the film industry from cultural to commercial sector. In competition against foreign films, Korean films resurged and started to be recognized internationally. Particularly, along with dramas, the film industry was one of the strong drivers for Hallyu, the Korean wave, which implies the popular trend of Koreas entertainment industry. There are two booms in the history of Koreas film industry: One, from the late 1950s to the mid-1960s and the other, after late 1990s until now. The agility, benchmarking, convergence, and dedication are useful to explain the success of this industry during these resurgent periods. A number of Korea filmmakers quickly learned American technology in the early phase. This allowed them to accumulate producing technology. With this technology, Korean film producers added Korean features to attract domestic audience. To achieve success from the early stage, the government employed various measures, aiming to make the industry self-sustainable by reinvesting profits gained from exportation. From the late 1990s until now, the ABCD framework can explain the success of Korean film industry more evidently. Around this time, private companies and government worked together for the success of industry within fairly short time span by investing huge amount of money in the infrastructure and production. Having been influenced immensely by American films and Hollywood companies, Koreas film industry imitated the storyline of American films and their distribution channel. However, Korean films and companies did not just imitate Hollywood films and business strategies, but also added more Korean-ness. Behind all the measures, there is a high dedication to foster the industry and to achieve success. It is noteworthy that the industrial policy of Korea was always export-oriented to overcome and improve beyond the industrys current status. Possessing abundant population, natural resources, and technology does not guarantee economic success. These concepts are included in the diamond model of Porter who emphasized the importance of competitive advantage of nations. However, this approach is limited to explain the initial development of East Asian countries as well as that of other advanced countries. The ABCD framework explains more comprehensively the economic achievement of these countries. Through rigorous theoretical review, statistical analysis, and case studies, these strategic variables are proven to be useful in enhancing industrial, corporate and national competitiveness. These findings can also give important implications for the economic planning of other countries.Abstract Introduction: The Need for a New Approach PART I. FOUNDATIONS 1. Rationales for Economic Prosperity 1: Classical Approaches 1.1 International trade theories 1.2 Productivity theories 2. Rationales for Economic Prosperity 2: Modern Approaches 2.1 Dynamic approaches 2.2 Sociological and other approaches 3. Rationales for Economic Prosperity 3: Porterian Approaches 3.1 The diamond model 3.2 The generalized double diamond model 4. The Need for a New Approach to Competitive Advantage 4.1 Problems of existing theories and need for a new approach PART II. NEW APPROACH 5. The ABCD Framework 5.1 The dynamics of the economic forces 5.1.1 Agility: Speed and precision 5.1.2 Benchmarking: Imitation and global standard 5.1.3 Convergence: Mixing and synergy-creation 5.1.4 Dedication: Diligence and goal-orientation 5.2 Theoretical back-ups 5.2.1 Agility: Speed and precision 5.2.2 Benchmarking: Imitation and global standard 5.2.3 Convergence: Mix and synergy-creation 5.2.4 Dedication: Diligence and goal-orientation 5.2.5 Comprehensiveness of the ABCD framework 6. Empirical Evidences 6.1 Operationalization of ABCD 6.1.1 Agility 6.1.2 Benchmarking 6.1.3 Convergence 6.1.4 Dedication 6.1.5 Reliability analysis 6.2 Variables 6.2.1 Dependent variable 6.2.2 Explanatory and control variables 6.3 Data and samples 6.4 Analysis methodology 6.5 Results 6.5.1 Results for cluster analysis 6.5.2 Results for ANOVA 6.5.3 Results for regression analysis 6.6 Discussion PART III. DEVELOPMENT OF KOREAN INDUSTRIES 7. Koreas Automobile Industry 7.1 Introduction to Koreas automobile industry 7.2 From liberation to Rhee Syngman regime (1945-1960) 7.2.1 Domestic and international circumstances 7.2.2 Evolutions of policies and business/corporate strategies 7.3 Park Chung-hee regime 1 (1962-1972) 7.3.1 Domestic and international circumstances 7.3.2 Evolutions of policies and business/corporate strategies 7.4 Park Chung-hee regime 2 (1973-1979) 7.4.1 Domestic and international circumstances 7.4.2 Evolutions of policies and business/corporate strategies 7.5 From Chun Doo-hwan to Roh Tae-woo regimes (1980-1992) 7.5.1 Domestic and international circumstances 7.5.2 Evolutions of policies and business/corporate strategies 7.6 From Kim Young-sam to Kim Dae-jung regimes (1993-2002) 7.6.1 Domestic and international circumstances 7.6.2 Evolutions of policies and business/corporate strategies 7.7 From Roh Moo-hyun to Lee Myung-bak regimes (2003-2013) 7.7.1 Domestic and international circumstances 7.7.2 Evolutions of policies and business/corporate strategies 7.8 The Dynamics of the forces 8. Koreas Film Industry 8.1 Introduction to Koreas film industry 8.2 From liberation to Rhee Syngman regime (1945-1960) 8.2.1 Domestic and international circumstances 8.2.2 Evolutions of policies and business/corporate strategies 8.3 Park Chung-hee regime 1 (1962-1972) 8.3.1 Domestic and international circumstances 8.3.2 Evolutions of policies and business/corporate strategies 8.4 Park Chung-hee regime 2 (1973-1979) 8.4.1 Domestic and international circumstances 8.4.2 Evolutions of policies and business/corporate strategies 8.5 From Chun Doo-hwan to Roh Tae-woo regimes (1980-1992) 8.5.1 Domestic and international circumstances 8.5.2 Evolutions of policies and business/corporate strategies 8.6 From Kim Young-sam to Kim Dae-jung regimes (1993-2002) 8.6.1 Domestic and international circumstances 8.6.2 Evolutions of policies and business/corporate strategies 8.7 From Roh Moo-hyun to Lee Myung-bak regimes (2003-2013) 8.7.1 Domestic and international circumstances 8.7.2 Evolutions of policies and business/corporate strategies 8.8 The dynamics of the forces Conclusion Bibliography Appendices 1. Data sets for ABCD 2. Dependent (GDP per capita, ppp) and control variables 3. Evolution of Koreas automobile companies 4. Motor vehicle production of Korea (1955-2012) 5. Motor vehicle export of Korea (1975-2012) 6. Korean film industry trends (1960-2013) 7. Korean film export trends (1970-2002) Chronology 1. Koreas automobile industry 2. Koreas film industryDocto

망간의 구조와 산화수가 산소 발생 촉매 작용에 미치는 영향에 대한 연구

학위논문 (석사)-- 서울대학교 대학원 : 재료공학부, 2014. 2. 남기태.The development of a water oxidation catalyst has been a demanding challenge for the realization of overall water-splitting systems. The asymmetric geometry and flexible ligation of the biological Mn4CaO5 cluster are important properties for the function of photosystem II, and these properties can be applied to the design of a new inorganic water oxidation catalyst. In part I, we identified a new crystal structure, Mn3(PO4)2-3H2O, that precipitates spontaneously in aqueous solution at room temperature and demonstrated its superior catalytic performance at neutral pH. Computational analysis indicated that phosphate ligations in our crystal make Mn-O bonding longer and more distorted than in other Mn-based oxides. Such structural flexibility can stabilize Jahn-Teller distorted Mn(III) and thus facilitate Mn(II) oxidation, as monitored by electron paramagnetic resonance spectroscopy. Moreover, although intensive studies have explored the role of Mn element in water oxidation catalysis, it has been difficult to understand whether the catalytic capability originates mainly from either the Mn arrangement or the Mn valency. In part II, to decouple these two factors and to investigate the role of Mn valency on catalysis, we selected a new pyrophosphate-based Mn compound (Li2MnP2O7), which has not been utilized for water oxidation catalysis to date, as a model system. Due to the monophasic behavior of Li2MnP2O7 with the delithiation, the Mn valency of Li2-xMnP2O7 (x = 0.3, 0.5, 1) can be controlled with negligible change in crystal framework (e.g. volume change ~ 1 %). Interestingly, we observed that as the averaged oxidation state of Mn in Li2-xMnP2O7 increases from 2 to 3, the catalytic performance is enhanced in the series Li2MnP2O7 < Li1.7MnP2O7 < Li1.5MnP2O7 < LiMnP2O7. Moreover, Li2MnP2O7 itself exhibits superior catalytic performance compared with MnO or MnO2 because of the highly distorted Mn geometry in Li2MnP2O7. In summary, we selected Mn3(PO4)2-3H2O and Li2-xMnP2O7 compounds as artificial platforms for understanding the effect of Mn structure and valency on water oxidation catalysis, respectively. We think that this study presents valuable guidelines for developing an efficient Mn-based catalyst which can be comparable with the biological Mn4CaO5 cluster in photosystem II under neutral conditions with controlled Mn valency and atomic arrangement.List of Tables 10 List of Figures 11 Chapter 1 Introduction 17 1.1 Energy Crisis and Demand for renewable energy 17 1.2 Water splitting 19 1.3 Oxygen Evolution reaction(OER) 21 1.3.1 Noble metal based OER electrocatalysts 24 1.3.2 Transition metal (Co,Ni,Cu,Fe) based OER electrocatalysts 26 1.4 Manganese based OER electrocatalysts 30 1.4.1 Photosystem II in biological system 30 1.4.2 Bio-inspired Mn based OER electrocatalysts 31 1.4.3 Bottleneck in Mn based electrocatalysts in OER 36 1.4.4 Importance for understanding the effect of Mn valency And Structure on water oxidation catalysis 37 Chapter 2 Mn3(PO4)2-3H2O : Effect on Mn structure 41 2.1 Experimental and Procedure 41 2.1.1 Synthesis and Materials 41 2.1.2 Characterization 42 2.1.2.1 Powder X-ray diffraction 42 2.1.2.1 ICP/MS 42 2.1.2.2 Rietveld analysis 43 2.1.2.3 Scanning electron microscopy(SEM) analysis 43 2.1.2.4 Transmission electron microscopy (TEM) analysis 44 2.1.2.5 BrunauerEmmettTeller (BET) method 44 2.1.3 Electrochemical analysis 46 2.1.3.1 Cyclic Voltammetry (CV) 46 2.1.3.2 Gas Chromatography (GC) 47 2.1.3 Electron paramagnetic resonance (EPR) spectroscopy 49 2.1.4 DFT calculation 51 2.2 Results and Discussions 52 2.2.1 Structural Characterization of Mn3(PO4)2-3H2O 52 2.2.2 Electrochemical analysis of Mn3(PO4)2-3H2O 64 2.2.3 Mechanistic studies of Mn3(PO4)2-3H2O 75 Chapter 3 Li2-xMnP2O7 (x= 0~1): Effect on Mn Valency 81 3.1 Experimental and Procedure 81 3.1.1 Synthesis and Material 81 3.1.2 Characterization 81 3.1.2.1 ICP/MS 82 3.1.2.2 Powder X-ray diffraction, Full-pattern matching 82 3.1.2.3 X-ray photon spectroscopy (XPS) 82 3.1.2.4 Transmission electron microscopy (TEM) analysis 83 3.1.2.5 BrunauerEmmettTeller (BET) method 83 3.1.3 Electrochemical analysis 84 3.1.4 DFT calculation 86 3.2 Results and Discussion 87 3.2.1 Structural Characterization of Li2-xMnP2O7 (x=0~1) 87 3.2.2 Electrochemical analysis of Li2-xMnP2O7 (x=0~1) 93 3.2.3 Mechanistic studies of Li2-xMnP2O7 (x=0~1) 112 Chapter 4 Conclusion 128 References 130 국문초록 138 감사의 글 (Acknowledgement) 140Maste

Clonal Fertility Variation and Genetic Characteristics at the Seed Orchards of Chamaecyparis obtusa in Gochang and Seogwipo, Korea

학위논문(박사) -- 서울대학교대학원 : 농업생명과학대학 농림생물자원학부, 2023. 2. 강규석.Chamaecyparis obtusa is a major tree species for wood production in Korea. It is straight and light and is used for interior and ship materials. It also has a scent and gloss, so widely used as a park or garden tree. In addition, it has various functional substances such as oil extracted from wood and fragrances extracted from cones. Therefore, it has recently been spotlighted as a preferred tree for afforestation, and planting is being attempted in various parts the country. C. obtusa is the most well-known species that can live in warm temperate zones, but the survival rate of planted trees tends to decrease significantly with climate. Therefore, it is urgent to supply excellent seeds and seedlings that can adapt to various climates. Seed orchards, the basis of forest tree breeding, are established to produce stably and supply genetically improved seeds. Genetic improvement refers to maximizing the characteristics and genetic structures of plus trees to be improved by transferring it on to the next generation (seed). By estimating the production capacity and contribution among clones and analyzing the genetic characteristics involved in the seed production process, the quality of seed orchard seeds can be proved and effective seed management methods can be suggested. This study was conducted to quantify some reproductive traits of C. obtusa. Over the past three years (2020~2022), the reproductive characteristics of 61 and 23 clones were surveyed in the seed orchards at Gochang and Seogwipo, Korea. The seed orchards were established in 2015 and 1969, respectively. In this study, the clonal contributions of male and female strobilus, and cone productions were estimated. It has been clearly shown that female and male parents contributed unequally to the gamete gene pool. Among the 61 clones at the seed orchard of Gochang, 12 to 15 clones (20 to 25% of the total) and 6 to 9 clones (10 to 15% of the total) produced 50% female and male strobili, respectively. The effective population numbers of female and male strobilus ranged from 23.64 (2021) to 37.38 (2022) and from 15.52 (2021) to 19.84 (2022) at gamete level, respectively. The effective population numbers at zygote (cone) level ranged from 20.15 (2022) to 35.94 (2021). Among the 23 clones at the seed orchard of Seogwipo, 1 to 5 clones (5 to 21% of the total) and 1 to 3 clones (5 to 15% of the total) produced 50% female and male strobili, respectively. Compared with the previous reports of other species, fewer clones contributed to the reproductive process in the seed orchards of C. obtusa. The effective population numbers of female and male strobilus ranged from 6.4 (2021) to 15.45 (2022) and from 4.32 (2021) to 9.58 (2022) at gamete level, respectively. The effective population numbers at zygote (cone) level ranged from 7.3 (2020) to 10.71 (2021), compared with the gamete level, more clones had contributed to reproductive process in the Seogwipo seed orchards. The individual heritabilities of female and male strobilus, and cone production ranged from 0.150 (2022) to 0.306 (2021), from 0.161 (2020) to 0.326 (2021), from 0.013 (2022) to 0.133 (2020), respectively in the seed orchard of Gochang. At the seed orchard of Seogwipo, the individual heritabilities of female and male strobilus, and cone production were estimated from 0.086 (2022) to 0.297 (2021), from 0.077 (2021) to 0.489 (2020), from 0.156 (2022) to 0.408 (2021), respectively. In both seed orchards, the clonal heritabilities were estimated to be higher than the individual heritabilities. The strobilus and cone production were positively correlated and statistically significant, except for the male strobilus and cone production at the seed orchard of Seogwipo in 2020. A total of 10 cones were collected per each individual tree for cone analysis over two consecutive years (2020∼2021). At the seed orchard of Gochang, the cones were analyzed to have 72.69% full-filled seeds, and 27.30% empty seeds, and 11.57% aborted ovules, so the seed efficiency was estimated to be 57.96% in 2020. In 2021, the cone had 56.43% full-filled seeds, and the 43.57% empty seeds, showing similar proportions of the full-filled seeds and empty seeds. The seed efficiency was estimated to be 46.98% that was slightly lower than in 2020. The germination rate per cone was very low with an average of 5.09%. The cones had 9.46% full-filled seeds, 90.54% empty seeds, and 33.06% aborted ovules. The seed efficiency was estimated to be 7.51% in 2020. In 2021, the cones had 25.77% full-filled seeds, 73.23% empty seeds, and 3.33% aborted ovules. Seed efficiency was higher than that in 2020, but the amount of full-filled seeds was lower. The average germination rate per clone was very low at 3.13%, which was similar to that of the seed orchard of Gochang. Parameters of the mating system and pollen flow were estimated using eleven nuclear microsatellite markers. At the seed orchard of Gochang, the expected heterozygosity (He) and the observed heterozygosity (Ho) were 0.740 and 0.796, respectively, in mother trees. The He and Ho were 0.702 and 0.765, respectively in seeds. Fixation indices (F) were -0.062 and -0.087 in mother trees and seeds, respectively. At the seed orchard of Seogwipo, the He and Ho were 0.683 and 0.667 in mother trees, and those were 0.704 and 0.826 in seeds, respectively. Fixation indices (F) were 0.037 in mother trees and -0.084 in seeds. From the analysis using MLTR, the outcrossing rate (tm), the biparental inbreeding (tm-ts), and the correlation of paternity (rp) were estimated to be 0.982, 0.028, and 0.172, respectively, at the seed orchard of Gochang. These values were similar to those analyzed using microsatellite markers in other Pinus species. At the seed orchard of Seogwipo, the tm, the (tm-ts), and the rp were 1.000, 0.059, and 0.064, respectively. From the analysis using CERVUS, the averages of outcrossing rate, pollen contamination rate, and selfing rate were estimated to be 94.21, 1.1, and 4.69%, respectively. The average number of pollen donors was 11.1 at the seed orchard of Gochang. The averages of outcrossing rate and selfing rate were 95.14 and 4.86%, respectively, at the seed orchard of Seogwipo. The average number of pollen donors was 10.8. Using TwoGener model for optimal pollen dispersal with the effective density of 130 trees per ha, the genetic differentiation level in pollen pool structure was estimated to be 0.134 at the seed orchard of Gochang. The average radial distance of pollen flow was calculated as 5.58 m. At the seed orchard of Seogwipo, the genetic differentiation level in pollen pool structure was estimated to be 0.330 with the effective density of 125 trees per ha. The average radial distance of pollen flow was calculated as 3.89 m. As the effective pollen dispersal in the population might be restricted, the amount of genetic variation could be maintained in each generation without loss of genetic diversity caused by selfing or inbreeding in seedlings at the seed orchard of Gochang and Seogwipo. The genetic diversity of pollen pool might be high at the seed orchard of Seogwipo, but the number of pollen donors at the seed orchard of Gochang were similar in the natural populations. Therefore, pollen donors should be managed to increase genetic diversity under completely random mating conditions at the seed orchard of Gochang.편백은 우리나라의 목재 생산을 위한 주요 수종으로, 통직하고 가벼우며 향기와 광택이 있어 내장재, 선박재 등으로 사용되고 공원수나 정원수로도 널리 이용된다. 또한 정유와 향료 등 다양한 기능성 물질이 많아 최근 조림 선호 수종으로 주목받고 있으며 다양한 지역에서 식재를 시도하고 있다. 하지만 난대 수종으로 기후에 따라 조림목의 생존율이 매우 감소하는 경향을 나타내기 때문에 다양한 기후에 적응이 가능한 우수 종자 및 종묘의 보급이 시급하다. 임목 육종의 바탕을 이루는 채종원의 조성 목적은 유전적으로 개량된 종자를 안정적으로 생산하고 보급하는 데 있다. 유전적 개량은 수형목으로 증식된 채종목 간 자연 교배를 통해 생산된 차대(종자)로 개량하고자 하는 모수의 특성과 유전 구조가 전이되어 극대화되는 것을 의미한다. 이와 관련하여 클론 간 배우자 생산 능력과 기여도를 추정하고, 이들의 종자 생산 과정에 관여하는 유전 특성을 분석함으로써 채종원산 종자의 품질을 증명하고 효과적인 채종원 관리 방안을 제시할 수 있다. 본 연구에서는 1969년에 조성된 서귀포 편백 채종원과 2015년에 조성된 고창 편백 채종원에서 3년간(2020~2022년) 개화량 및 구과 생산량을 조사하여 얻은 자료를 토대로 생식 과정에 관계된 몇 가지 특성을 계량화하였다. 고창 채종원에서의 경우 61개 클론 중 전체 개화량의 50%에 기여하는 암구화의 상대적인 비율은 20~25%이었으며, 수구화의 상대적인 비율은 10~15%로 나타나 암구화가 수구화보다 다소 높게 나타났다. 배우체 수준에서 유효 집단 크기는 암구화의 경우 23.64(2021)~37.38(2022년) 이었으며, 수구화는 15.52(2021)~19.84(2022년)로 암구화보다 다소 낮게 추정되었고, 구과 수준에서는 20.15(2022)~35.94(2021년)로 추정되었다. 서귀포 채종원에서는 23개 클론 중 전체 개화량의 50%에 기여하는 암구화의 상대적인 비율이 5~21%이었으며, 수구화의 상대적인 비율은 5~15%로 나타나 고창 채종원에서와 마찬가지로 암구화가 수구화보다 다소 높게 나타났으며 소수 클론에 의해 편중되는 현상이 다른 수종에 비하여 높게 나타났다. 배우체 수준에서 유효 집단 크기는 암구화의 경우 6.40(2021)~15.45(2022년), 수구화의 경우 4.32(2021) ~9.58(2022년)로 암구화에 비해 다소 낮게 추정되었으며, 구과의 경우 7.30(2020)~10.71(2021년)로 추정되어 배우체 수준보다 높게 나타났다. 고창 채종원에서의 클론 간 개화량에 대한 개체 유전력은 암구화의 경우 0.150(2022)~0.309(2021년), 수구화는 0.161(2020)~0.326 (2021년), 구과는 0.013(2022)~0.133(2020년)으로 접합자 수준에서의 유전력이 낮게 추정되었다. 서귀포 채종원에서의 클론 간 개화량에 대한 개체 유전력은 암구화의 경우 0.086(2022)~0.297(2021년), 수구화의 경우 0.077(2021)~0.489(2020년)로 추정되었으며, 구과는 0.156(2022)~ 0.408(2021년)로 추정되었다. 그리고 두 채종원 모두에서 개체 유전력보다 클론 유전력이 매우 높았다. 암, 수구화 개화량과 구과 생산량 간 상관분석 결과, 2020년도 서귀포 채종원에서의 수구화와 구과 생산량은 유의한 상관을 보이지 않았으며, 이를 제외한 나머지는 모두 유의한 정의 상관을 보였다. 2020년부터 2021년까지 2년간 고창과 서귀포 채종원에서 전수로부터 개체목당 10개 구과를 채취하여, 클론 간 구과와 종자의 특성을 분석하였다. 고창 채종원에서의 경우 2020년의 충실 종자율은 72.69%, 비립 종자율은 27.31%, 고사 배주율은 11.57%, 종자 효율은 57.96%로 추정되었다. 2021년의 충실 종자율은 56.43%, 비립 종자율은 43.57%로 충실 종자율과 비립 종자율의 비율이 유사하였다. 종자 효율은 46.98%로 추정되어 2020년에 비해 다소 낮게 나타났으며, 발아율은 클론당 평균 5.09%로 매우 저조하였다. 서귀포 채종원에서의 경우 2020년의 충실 종자율은 9.46%, 비립 종자율은 90.54%, 고사 배주율은 33.06%로 확인되어 충실 종자 결실이 매우 저조하였으며, 종자 효율이 7.51%로 낮게 추정되었다. 2021년의 충실 종자율은 25.77%, 비립 종자율은 74.23%, 고사 배주율은 3.33%로 추정되었다. 종자 효율은 24.36%로 2020년에 비해 종자 효율은 증가하였지만 충실 종자 결실이 저조하였다. 클론당 평균 발아율은 3.13%로 고창 채종원에서와 마찬가지로 매우 저조하였다. 고창과 서귀포 채종원의 유전 모수를 확인하기 위하여 microsatellite 표지를 이용하여 2021년에 생산된 성숙 종자를 대상으로 타가 교배율과 화분 오염률, 근친 교배율을 확인하였다. 고창 채종원의 모수에서 확인된 이형 접합도 기대치는 0.740이었으며, 관측치는 0.796으로 추정되었다. 종자에서 확인된 이형 접합도 기대치는 0.702이었으며, 관측치는 0.756이었다. 모수와 종자의 고정지수는 각각 -0.062와 -0.074로 나타났다. 서귀포 채종원의 모수에서 이형 접합도 기대치는 0.683이었으며, 관측치는 0.667로 확인되었다. 종자에서 확인된 이형 접합도 기대치는 0.704이었으며, 관측치는 0.740으로 추정되었다. 모수와 종자의 고정지수는 각각 0.037과 -0.206으로 도출되었다. MLTR 프로그램을 이용하여 분석한 타가 교배율은 고창의 경우 0.982이었으며, 근친 교배율은 0.028이었다. 부계 상관은 0.172로 추정되었다. 서귀포 채종원에서의 경우 타가 교배율은 0.100으로 매우 높게 추정되었으며, 근친 교배율은 0.059로 산출되었다. 부계 상관은 0.064로 추정되었다. CERVUS 프로그램을 이용하여 분석한 고창 채종원에서의 타가 교배율은 클론 간 평균 94.21%였으며, MLTR 프로그램으로 분석한 결과와 유사하였다. 화분 오염률은 1.1%, 자가 교배율은 4.69%로 추정되었으며 기여 화분친 수는 평균 11.1개이었다. 서귀포 채종원에서의 경우 타가 교배율은 95.14%, 자가 교배율은 4.86%로 확인되었으며 기여 화분친 수는 평균 10.8개로 확인되었다. TwoGener 방법으로 화분원의 분산을 확인한 결과, 고창 채종원에서의 경우 임분 밀도를 ha당 130본으로 하였을 때 화분원의 유전적 분화는 0.134였으며, 평균 유효 화분 이동 거리는 5.990m로 추정되었다. 서귀포 채종원에서의 경우 임분 밀도를 ha당 125본으로 추정하였으며, 화분원의 유전적 분화는 0.330이었고, 평균 화분 이동거리는 3.892m로 추정되었다. 이와 같이 고창과 서귀포 편백 채종원 모두 타가 교배율이 높게 추정되었으므로, 채종원산 종자로 생산된 편백 묘목의 경우 자가 교배로 인한 근교약세가 원인이 되는 불량 형질은 발생할 가능성이 낮을 것으로 기대되었다. 하지만 기여 화분친 수의 비율이 고창 편백 채종원의 경우 자연 집단에서 기여하는 화분친 수와 유사하게 나타나 유전 다양성을 높이기 위한 화분원의 관리가 필요할 것으로 판단되었다.제1장 서론 １ 제1절 연구의 배경 및 필요성 １ 제2절 연구 목적 ４ 제2장 연구사 ６ 제1절 편백(C. obtusa)의 유전 및 생태 ６ 제2절 채종원 내 개화결실량 변이 연구 12 제3절 채종원산 종자의 구과 분석 20 제4절 DNA 표지를 이용한 교배 양식 연구 23 제3장 재료 및 방법 30 제1절 연구 대상지 현황 30 제2절 개화 및 구과 생산량 32 제3절 구과 및 종자 특성 분석 33 제4절 통계 분석 및 유전력 추정 37 제5절 누적 기여도 곡선 37 제6절 유효 집단 크기 및 유전 다양성 추정 39 제7절 Microsatellite 표지 분석 40 제8절 유전 구조 및 교배 양식 분석 44 제4장 결과 48 제1절 개화결실량 48 1.1 클론 간 개화량 및 구과 생산량 변이 48 1.2 누적 기여도 곡선 50 1.3 유효 집단 크기 및 유전 다양성 추정 53 1.4 유전력 추정 55 1.5 개화 및 구과 생산량 간 상관관계 분석 61 제2절 구과 및 종자의 유전 다양성 64 2.1 구과의 형태적 특성 64 2.2 종자 특성 분석 66 2.3 구과 및 종자 특성의 유전력 추정 69 2.4 구과 및 종자 특성 간 상관관계 분석 71 2.5 발아력 검정 75 제3절 교배 양식 분석 75 3.1 유전 다양성 분석 75 3.2 교배 양식 84 3.3 화분원의 유전적 분화 86 3.4 부계 유전자형 및 화분 오염률 추정 86 제5장 고찰 94 제1절 개화량 및 구과 결실량 변이와 유전 다양성 94 제2절 구과 분석 및 종자 특성 분석 99 제3절 교배 양식 분석 105 제6장 결론 114 참고 문헌 117 Appendix 141 Abstract 240박

편지

한 사람이 있었다. 그 사람은 종종 내게 편지를 써서 주곤 했다. 그 편지에는 때로는 격려와 지지의 따스한 말들이, 때로는 남들이 쉽게 하지 못할 날카로운 충고가 담겨 있었다. 나는 꼭 그 사람의 편지들을 두어 번씩 되뇌어 읽곤 했었는데, 그 이유는 그 사람의 편지가 화려한 미사여구로 쓰여 있었다거나 기교적으로 잘 쓴 글이었기 때문이라기보다는, 간결했지만 늘 다시 읽어보고 싶을 만큼 마음에 와 닿았기 때문이었다. 그리고 언제나 나를 배려하고 존중하는 마음이 느껴지는 것이었기에 그 사람의 편지는 나를 웃게도 하고 울게도 하는 마법같은 것이었다. 그 사람의 편지가 내게 주었던 감동을 기억하며, 글쓰기에 대한 몇 가지를 이야기하고자 한다. 무엇보다도 글쓰기는 애정의 표현이라는 생각이 든다. 글을 쓰는 대상에 대한, 글을 읽는 사람에 대한, 멀게는 공동체에 대한 애정부터 가깝게는 나 자신에 대한 애정까지 그 어떤 것에 대한 것이든 애정 없이는 글을 쓰기 어렵다. 나에 대한 애정이 있었기 때문에 그 사람은 내게 편지를 썼을 것이다. 비단 그 사람의 편지만이 아니다. 눈 내린 다음 날 이름 모를 누군가가 붙여 놓았을, 미끄러지지 않도록 조심하라는 종이 한 장에서부터 하루하루 변화하는 정세 속에서 매일같이 나라를 걱정하는 조간신문의 어느 기사글, 그동안 보고 배우고 알게 된 것들을 기록한 논문에 이르기까지 그 모든 것이 애정, 특히 소통하고자 하는 애정이 없었다면 우리의 곁에 남을 수 없었을 것이다

Elevated levels of preoperative CA 15-3 and CEA serum levels have independently poor prognostic significance in breast cancer

BACKGROUND: To evaluate the prognostic value of preoperative tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA), in breast cancers. PATIENTS AND METHODS: Preoperative CA 15-3 and CEA levels of 1681 patients were measured. The association of both tumor markers levels with clinicopathological parameters and outcomes was investigated by univariate and multivariate analyses. RESULTS: Among 1681 patients, elevated preoperative CA15-3 and CEA levels were identified in 176 and 131 patients, respectively. Higher preoperative CA 15-3 and CEA levels were significantly associated with a larger tumor size, axillary node metastases, and advanced stage. Patients with elevated CA 15-3 and CEA levels showed worse survival, even in stage-matched analysis. Patients with normal levels of both CA15-3 and CEA showed better survival than those with one or both markers levels elevated. In multivariate analysis, elevated preoperative CA 15-3 and CEA levels were independent prognostic factors. The statistical significance of elevated preoperative tumor markers levels on survival was solidified with longer follow-up and larger study population. CONCLUSIONS: Elevated preoperative CA 15-3 and CEA levels are associated with tumor burden and showed independent prognostic significance. Therefore, new treatment strategies are necessary for patients with elevated preoperative CA 15-3 and CEA levels in clinical practice.ope

Homeodomain-interacting protein kinase 1 (HIPK1) expression in breast cancer tissues

OBJECTIVE: This study investigated the incidence and clinical significance of homeodomain-interacting protein kinase 1 expression in breast cancer patients. METHODS: We investigated immunohistochemical homeodomain-interacting protein kinase 1 expression from tissue microarrays of 1032 patients. The association of homeodomain-interacting protein kinase 1 expression pattern, clinicopathologic factors and survival outcome was evaluated. Tumors with ≥10% stained cells were considered positive for homeodomain-interacting protein kinase 1. RESULTS: Non-cancerous breast tissue, pTis and pT1mic lesions did not show homeodomain-interacting protein kinase 1 expression at any sites. Of the 859 invasive tumors, 124 (14.4%) showed homeodomain-interacting protein kinase 1 expression with three different expression patterns: cytoplasmic (2.4%), nuclear (6.3%), and both cytoplasmic and nuclear (5.7%). Cytoplasmic homeodomain-interacting protein kinase 1-positive tumors showed distinctive features such as fewer nodal metastases, but were frequently Grade III, estrogen receptor-negative, progesterone receptor-negative, HER2-positive, highly proliferative and molecular apocrine tumors. No significant difference in clinicopathologic features was identified between negative and nuclear homeodomain-interacting protein kinase 1-positive tumors. Both cytoplasmic and nuclear HIPK1-positive tumors represent frequent small size, node negativity and moderately differentiated features. Survival was not significantly different by homeodomain-interacting protein kinase 1 expression patterns. CONCLUSIONS: Homeodomain-interacting protein kinase 1 expression was identified only in invasive breast cancer cells with three different patterns: cytoplasmic, nuclear, and both cytoplasmic and nuclear. Although the mechanism is not certain, the subcellular localization of HIPK1 expression is associated with tumor histopathologic characteristics and different functions.ope

Comparing competitiveness of India and China : Are they competing or cooperating?

Thesis(masters) --서울대학교 대학원 :국제학과(국제통상전공),2008. 8.Maste