이종 생물학적 데이터 간의 연결 및 통합: 다중 모달 데이터 통합 기반의 오믹스 데이터 비교분석 및 약물 반응 예측을 위한 컴퓨터적 계산 방법론

학위논문(박사) -- 서울대학교대학원 : 공과대학 컴퓨터공학부, 2024. 2. 김선.Molecular biological data includes various omics, including genome, transcriptome, proteome, pathway, interactomes as well as perturbagens that disrupt these omics. Each data type provides information on specific or partial aspects of biological systems. For more comprehensive understanding of the functionality and mechanisms of biological organisms, it is crucial to utilize various types of data together. Indeed, recent bioinformatics tasks involve using multiple types of data from different sources for the prediction of biological functions. However, such integrative analysis poses several challenges. Firstly, biological data is high-dimensional but has a relatively low sample size due to experimental costs and time constraints as well as ethical considerations. Secondly, each type of biological data takes on different shapes in terms of data structure, and is complex in nature resulting in inconsistencies among them. Moreover, entities in biological systems do not function independently. They interact with each other, thus considering interactions among biological entities is very important. Therefore, computational methods are required to create links between different types of data or summarize the inconsistencies observed in the data. This doctoral study aims to address these challenges by developing novel computational methods that can integrate, compare and link different omics data, thus analysis of biological data can be enhanced. The first study addresses the problem of effectively comparing transcriptome and proteome abundance data, which do not agree to a large degree. This discrepancy often arises when attempting to perform comparative analysis on phenotypes across multiple cancers. A significant challenge is to find a link that can connect or align the dimensions of these various types of data. For this goal, we utilized protein subcellular localization, a factor closely related to protein function. We developed a visual data mining system, ALPACA (A Location-wise Proteome/transcriptome Abundance Comparative Analyzer) that can be used to perform comparative analysis. The proposed system visualizes differences among multiple abundance data for concise and effective summarization and provides guidance for users to explore various combinations of cancer types and omics. ALPACA achieves this by showing differences in biological pathway and location enrichment distributions in terms of information theory-based metrics. Thus, the system offers a new approach for navigating the complex landscape of multi-omics integration in cancer research. The second study is to develop a deep learning-based framework for enhanced prediction of drug response by integrating multiple sources of data such as transcriptomic profiles, drug chemical properties and protein-protein-interaction network data. For drug response prediction, it is important to incorporate drug target information, considering that drugs work by targeting and disrupting specific target proteins which then alters the overall cell state. The primary challenge for the integration is the lack of transcriptome data after drug treatment. Since there is no data regarding the effect of the drug on the whole cell, the downstream drug response prediction cannot be performed while taking drug target information into account. To overcome this challenge, we developed an algorithm that simulates changes in cell states when a drug is applied. We addressed this issue by utilizing drug target information and protein-protein-interaction network as links between drugs and cell line transcriptomes during the prediction of drug responses. We also proposed a model-agnostic deep-learning framework that can combine the resulting gene perturbation profile generated using our algorithm with any drug response prediction model. The results support that integrating drug target information can enhance the predictive performance of existing models and that the proposed framework indeed takes advantage of the biological mechanism for the prediction. The third study is to design and develop a deep learning framework based on graph neural network (GNN) that performs sample-wise gene selection with drug target and heterogeneous network. The high dimensionality of genes and small sample size of biological data often result in poor prediction performance for most biological prediction tasks due to overfitting. The limitation of state-of-the-art techniques that reduce gene-feature dimension is that they do not consider the characteristics of drugs and are therefore not specific to each drug. The main challenge here is the lack of connection between drug and cell line data that can enable selection of genes that are related to the biological mechanism of drug. We present a deep learning framework that constructs a network tailored for each drug based on gene-set that well represents drug's mechanism, and selects genes related to the mechanism of each drug using GNN. The results support that this novel method of drug-specific gene selection improved performance of the downstream drug response prediction. In conclusion, this dissertation proposes novel approaches to the integrated analysis of complex biological datasets. The presented studies are expected to contribute towards our ability to effectively extract knowledge from the growing wealth of biological information.생물학 데이터는 유전체, 전사체, 단백질체, 생물학적 경로 등을 비롯한 여러 오믹스 이외에도, 데이터 개체들간의 상호작용체 (interactome), 그리고 오믹스를 교란시키는 약물이나 화합물과 같은 교란체 (perturbagen)까지, 다양한 수준의 복잡성을 띄고 있다. 이들 오믹스 데이터는 각각 생물 시스템에 대한 특정 측면에서의 정보를 담고 있다. 따라서, 생물의 기능과 메커니즘에 대한 보다 포괄적인 이해를 위해서는 다양한 유형의 데이터를 함께 활용하는 것이 중요하다. 실제로, 최근의 생물정보학 분야에서는 생물의 기능을 예측하기 위해 다양한 데이터를 함께 활용하려는 시도들이 이어지고 있다. 하지만, 이렇게 서로 다른 형태와 성질의 데이터를 한번에 분석하는 것은 어려운 문제이다. 먼저, 생물학 데이터는 고차원적이지만 그에 비해 표본 크기가 작다. 실험할 때 드는 시간과 비용, 윤리적인 문제 등으로, 기계학습 등 인공지능 기술을 활용하는 다른 분야들에 비해 표본 수가 부족하다. 이와 동시에 32억개의 염기쌍 서열로 이루어진 DNA 유전체, 2만 여개의 유전자와 단백질, 1400만개의 단백질 상호작용, 수백개의 약물 등 차원이 매우 높다. 또한, 각 종류의 생물 데이터는 서열, 실수 값으로 이루어진 행렬, 그래프 등 서로 형태가 다르고 이들 간의 불일치성도 높다. 그렇기 때문에 서로 다른 데이터 종류 간의 연결을 시켜줄 수 있는 연결고리, 혹은 이들의 정보를 요약, 관측 할 수 있는 분석 방법이 필요하다. 그리고, 생물 시스템의 개체들은 각각 따로 기능하지 않고, 서로 상호작용을 하며 기능을 하기 때문에 이들 간의 관계를 함께 고려하여 분석을 하는 것이 매우 중요하다. 본 박사학위 논문에서는 이러한 한계점들을 해결하기 위해 서로 다른 오믹스 데이터를 연결 및 비교하는 새로운 계산 방법론들을 개발함으로써 생물 데이터의 분석을 향상시키는 데 목표를 두고 있다. 첫 번째 연구는 서로 같은 샘플, 같은 유전자를 나타내는 데도 불구하고 서로 정보가 일치하지 않는 전사체와 단백질 발현량 데이터를 효과적으로 연결 및 비교 분석할 수 있는 방법론을 제시하고자 하였다. 해당 연구는 여러 암종의 다중 오믹스 발현량 데이터를 세포 내 단백질 위치 정보의 관점에서 비교 분석해주는 시각적 데이터 마이닝 시스템을 개발한 연구이다. 서로 다른 오믹스들 간의 데이터가 서로 일치하지 않는 다는 문제점에 대응하기 위해, 이들을 연결시켜줄 중간 다리로써 단백질 위치 데이터를 활용하였으며, 이들의 차이를 효과적으로 요약하여 시각적으로 표현해 주고 비교 분석할 수 있는 시스템을 구축한 것이다. 제시한 시스템을 통해 다양한 암종의 발현량 데이터를 비교하여 이들간의 표현형적 차이를 야기하는 후보 바이오마커 단백질들을 발굴 할 수 있었다. 두 번째 연구는 전사체 정보, 약물 화학적 구조 정보, 단백질-단백질 상호작용 네트워크, 생물학적 경로 등 다양한 종류의 데이터를 이용해 약물에 대한 세포주의 반응을 예측하는 Model-agnostic한 딥러닝 프레임워크를 제시한다. 현재, 대규모 공개 데이터베이스에서 제공되는 약물을 친 후의 전사체 데이터가 부족하기 때문에 대다수의 약물 반응 예측 연구에서는 약물을 치기 전의 세포주 정보와 약물의 정보만을 사용하여 약물 반응을 예측하고 있다. 본 연구에서는 이를 해결하기 위해 약물의 표적 단백질 정보와 단백질 상호작용 정보를 활용하여 약물이 세포에 미치는 영향을 시뮬레이션하는 알고리즘을 개발하였다. 이를 통해 약물이 표적 단백질에 작용하였을 때 전사체 전체가 어떻게 영향을 받을지 예측해 볼 수 있었고, 기존의 여러 딥러닝 기반 약물 반응 예측 모델들의 성능을 향상시킬 수 있었다. 세 번째 연구는 약물 표적 정보와 이종 네트워크를 통해 약물 및 세포주 표본 특이적으로 유전자를 선별해주고 결과적으로 약물 반응 예측을 향상 시켜주는 그래프 신경망 (GNN) 모델을 제시한다. 현재 약물 반응과 같이 약물과 세포의 오믹스 데이터를 함께 사용하는 생물정보학적 문제들은 고차원 및 저표본 (high-dimension, low-sample) 문제를 겪고 있다. 특히, 세포주 데이터의 경우, 단백질 코딩 유전자 수만 2만여 개에 달하기 때문에 대다수의 약물 반응 예측 연구에서는 다양한 방법을 통해 데이터의 유전자를 선별하여 사용하고 있다. 하지만, 현재 주로 사용되고 있는 유전자 차원 축소 기법들은 약물의 특성을 고려하지 않고 있기 때문에 각 약물에 대해 특이적이지 않다는 문제가 있다. 해당 연구에서는 딥러닝 모델로 하여금 약물과 표본에 대해 특이적으로 유전자를 선별하는 방식으로 차원을 줄이고자 한다. 이를 위해, 약물의 표적 정보를 활용하여 약물 별로 이종 네트워크를 구축하는 등 서로 다른 데이터를 통합 활용하여 기존 유전자 선별 방식보다 예측을 향상 시켜줄 수 있는 방법론을 제시한다. 결과적으로, 제시한 모델을 통해 기존 다른 유전자 선별 방식보다 약물 반응 예측 성능을 향상 시킬 수 있었고, 약물의 메커니즘과 관련된 유전자들을 살펴볼 수 있는 등 예측 모델에 해석력 또한 더할 수 있었다. 결론적으로, 본 박사학위 논문은 다중 모달 생물 데이터에 대한 통합 분석 방법론을 제시한다. 복잡한 생물 데이터셋 내에서의 효과적인 탐색뿐만 아니라, 서로 다른 두 데이터를 연결시킴으로 인해 생물 문제의 예측의 성능을 향상 시킬 수 있었다.Abstract i Chapter 1 Introduction 1 1.1 Multi-modality of data in bioinformatics 2 1.1.1 Biological omics data 2 1.1.2 Perturbagen data 3 1.1.3 Computational challenges in multi-modal analysis 4 1.2 Formulating computational problems for the integrative analysis of multi-modal data 6 1.2.1 Background concepts in bioinformatic tasks that use multi-modal data 6 1.2.2 Effective representation of discrepancies between omics data 6 1.2.3 Prediction of drug response from drug chemical property and cell line genomic data 9 1.3 Three computation problems for the integrative analysis of multi-modal data 11 1.4 Outline of the dissertation 16 Chapter 2 ALPACA: A Visual Data Mining System for Subcellular Location-specific Knowledge Mining from Multi-Omics Data in Cancer 17 2.1 Motivation 18 2.1.1 Inconsistency between Transcriptome and Proteome Abundance 19 2.1.2 Importance of Spatial Distributions of proteins at Subcellular Location Level 19 2.1.3 Existing Work 20 2.1.4 Introduction to ALPACA 21 2.2 Methods 23 2.2.1 Data 23 2.2.2 A Location-wise Proteome/transcriptome Abundance Comparative Analyzer (ALPACA) 25 2.3 Results 28 2.3.1 Demonstration of the Power of Location Information Use in Disease Gene Detection Analysis 28 2.3.2 Data Mining Case Study1 (Breast Cancer Subtypes) 31 2.3.3 Data Mining Case Study2 (Gynaecological Cancers) 33 2.4 Discussions and Conclusion 35 Chapter 3 Improved Drug Response Prediction by Drug Target Data Integration via Network-based Profiling 49 3.1 Motivation 50 3.1.1 Related Work 51 3.1.2 Proposed Approach 53 3.2 Methods 55 3.2.1 Drug Response Prediction Strategy using Drug Target Information 55 3.2.2 Experimental Setup 60 3.2.3 Evaluation Criteria 63 3.2.4 Data 64 3.3 Results 65 3.3.1 Drugs that share common target proteins have similar drug response trend 65 3.3.2 Gene perturbation simulation reflect actual gene perturbations 66 3.3.3 Drug response prediction performance using drug target data integration 67 3.3.4 Comparisons of gene perturbation profile extraction methods 69 3.3.5 Case Study: Investigation on performance improvement mechanism of Doxorubicin via gene importance analysis 70 3.3.6 Use of gene perturbation profile boosts prediction performance, especially for drugs with explicit target proteins known 71 3.4 Discussions and Conclusion 71 Chapter 4 Exploiting Drug – Protein Interactions for Drug-specific Gene Selection via Graph Neural Networks 80 4.1 Motivation 81 4.1.1 Backgrounds 81 4.1.2 Computational Challenges 82 4.1.3 Related Work 82 4.2 Methods 86 4.2.1 Data 86 4.2.2 Model Structure 88 4.2.3 Gene-Selection Step 88 4.2.4 Drug Response Prediction Step 92 4.2.5 Experimental Setup 93 4.3 Results 95 4.3.1 Gene-Selection Methods Comparison 95 4.3.2 Drug Response Prediction Performance Comparison to SOTA Models 96 4.3.3 Ablation Study 98 4.3.4 Case Study: Selected Gene Set Investigation 99 4.4 Discussions and Conclusion 100 Chapter 5 Conclusions 102 Appendix A Multi-modal Data Entities 106 초록 125 감사의 글 128박

Studies on factors affecting beef taste and the effects of dietary glycerin on growth performance and carcass characteristics in Korean cattle steers

학위논문 (박사)-- 서울대학교 대학원 : 농업생명과학대학 농생명공학부, 2018. 2. 백명기.Beef marbling score and quality grade positively affect meat sensory characteristics, including tenderness, juiciness, flavor, and overall palatability. Korean cattle beef is well known for good palatability because of the high quality grade and thus high marbling. Limited information is available and variability exists in data on the associations among marbling score/quality grade, meat characteristics, and sensory traits in Korean cattle beef. Korean consumers prefer Korean cattle beef to domestic Holstein and imported beef because they believe that the palatability of Korean cattle beef is superior to that of other breeds. Limited information is available on the factors that affect the preference of Korean consumers for Korean cattle beef over other breeds. Two studies (study 1 and 2) were conducted to elucidate 1) the associations among quality grade/marbling and various carcass characteristics and sensory traits in Korean cattle beef, and 2) the factors that contribute to differences in the sensory traits of longissimus thoracis of different breeds. Glycerol, a by-product with biodiesel, also known as glycerin, serves as gluconeogenic substrate in the liver and kidney, and it has an energy value similar to corn on a pound-for-pound basis in dairy and feedlot cattle. Although many studies were conducted for the effect of glycerin on carcass composition and characteristics in various animal diets, the outcomes were not consistent. Also, limited information is available for effects of glycerin supplementation on meat characteristics in Korean cattle steers. Two studies (study 3 and 4) were conducted to identify 3) the effects of dietary glycerin replacement on growth performance, carcass characteristics and sensory traits in Korean cattle steers fed diets based on the similar TDN level between experimental diets, and 4) the effects of crude glycerin supplementation on growth performance and carcass characteristics in Korean cattle steers fed diets based on the different TDN level between experimental diets. 1. Comparison of carcass and sensory traits, fatty acid profiles and volatile compounds among quality grades in longissimus dorsi and semimembranosus muscles of Korean cattle steer This study was performed to compare carcass traits, sensory characteristics, physicochemical composition, nucleotides and collagen content, free amino acids, content and composition of fatty acids (FA), and volatile compounds among four quality grades (QG1++, 1+, 1, and 2), and to understand their association with carcass characteristics in longissimus dorsi (loin) and semimembranosus (rump) cuts of Korean cattle steers. This study confirms that marbling score (MS) and intramuscular fat (IMF) content are major positive determinants of QG in Korean cattle beef. Numeric values of tenderness, juiciness, and overall acceptability in loin tended to be highest in QG1++, and those of juiciness and overall acceptability tended to be lowest in QG 2. Juiciness and overall acceptability were strongly correlated with QG. Our results demonstrated that QGs are linked to sensory traits. However, the nucleotide contents including inosine monophosphate (IMP) may not be major factors determining meat palatability of Korean cattle beef in this study. Glutamic acid and proline were significantly associated with tenderness, juiciness, and overall acceptability, although they did not differ significantly among QGs. In addition, beef QGs affected the compositions and contents of FAs and volatile compounds in loin and rump. Loin FA percentages, especially those of oleic acid (C18:1n9) and monounsaturated FA (MUFA), generally increased with increasing QGs. Some volatile compounds in loin and rump varied with QGs and were positively or negatively correlated with flavor. 2. Comparison of reducing sugar content, sensory traits, and fatty acids and volatile compound profiles of longissimus thoracis among Korean cattle, Holsteins, and Angus steers This study was performed to compare intramuscular fat (IMF) and reducing sugar contents, sensory traits, and fatty acid (FA) and volatile compound profiles in longissimus thoracis (LT) among Korean cattle (KC), Holstein (HO), and Angus (AN) steers. The IMF, reducing sugar content, and sensory traits of the LT varied among KC, HO, and AN steers. The KC LT had the highest IMF and reducing sugar contents, and the best sensory traits (flavor, tenderness, juiciness, and overall acceptance). The IMF and reducing sugar contents were positively correlated with all of the sensory traits, suggesting that these factors may positively affect beef flavor. Palmitic acid (C16:0), oleic acid (C18:1n9), and monounsaturated FA (MUFA) may positively affect sensory traits, whereas linoleic acid (C18:2), and polyunsaturated FA (PUFA) may negatively affect sensory traits. The percentages of different volatile compounds in the LT also varied among the three breeds. The KC had the highest percentage of volatile compounds, including acetaldehyde, 3-methyl butanal, and 3-hydroxy-2-butanone, and these compounds were positively correlated with flavor. Our results demonstrated that variations in IMF, reducing sugar content, and FA and volatile compound profiles may contribute to differences in the sensory characteristics of the LT among breeds. The results of this study enhance our understanding of the association of reducing sugar and volatile compound contents with the sensory traits of beef. This information may help in determining beef palatability. 3. Effects of dietary glycerin replacement on growth performance and rumen and carcass characteristics in Korean cattle steers The study was performed to evaluate the effect of 3% dietary glycerin replacement on growth performance, blood metabolites, ruminal fermentation characteristics, carcass characteristics and sensory traits, hepatic gluconeogenic gene expression, and muscle glycogen contents in Korean cattle steers. Glycerin replacement in the finishing diet of Korean cattle steers had no impact on weight gain, average daily gain, and feed efficiency except for increase in average daily concentrate intake. This increased intake may be attributed to the sweet taste of glycerins property. Glycerin replacement did not affect carcass characteristics, chemical and physico-chemical composition, reducing sugar, glycogen, collagen, nucleotides, fatty acid, volatile compounds, and sensory traits in the longissimus thoracis. These results indicate that the glycerin inclusion level (3%) may be not enough to improve animal performance and carcass characteristics. In addition, feeding concentrate containing 3% of glycerin did not result in detrimental effects on growth performance, ruminal fermentation, animals physical condition, and metabolism. This is important not only on animal performance and carcass characteristics but also for sustainable and economic aspects because glycerin is a biodiesel residue and it can potentially partially replace some expensive ingredients such as corn, molasses, distillers dried grains with solubles as an energy source for beef cattle. 4. Effect of dietary crude glycerin supplementation on performance, blood metabolites, ruminal fermentation parameters, and carcass characteristics in Korean cattle steers This study was performed to evaluate the effect of dietary glycerin supplementation on growth performance, blood metabolites, ruminal fermentation characteristics, carcass characteristics and sensory traits, glycogen content in liver and muscle, and hepatic gluconeogenesis gene expression in Korean cattle steers finished in feedlot. This study confirms that dietary glycerin supplementation at 6.4% of DM did not lead to detrimental effect on feed intake in Korean cattle steers. Both glycerin and corn starch supplementation did not improve average daily gain and feed efficiency in Korean cattle steers. Glycerin supplementation also did not affect rumen fermentation characteristics, carcass characteristics, IMF content, reducing sugar content, glycogen content in both liver and muscle, and sensory traits of Korean cattle steers. Both glycerin and corn starch supplementation did not affect serum glucose concentration at initial and 8th week, but glycerin supplementation slightly increased the average serum glucose concentration at 16th week. Although glycerin supplementation had no impact on carcass and meat quality, glycerin could be potentially considered as a good energy source to maintain the animals metabolism in finishing Korean cattle.CHAPTER ONE 1 GENERAL INTRODUCTION 1 CHAPTER TWO 4 LITERATURE REVIEW 4 1. Overview of Korean cattle 4 1) History of Korean cattle 4 2) Korean cattle industry 5 3) Beef quality grading system in Korea 7 4) Characteristics of Korean cattle beef 8 2. Factors affecting sensory traits 12 1) Tenderness 12 2) Flavor 13 3) Juiciness 17 4) Precursors of flavor 17 3. Glycerin as feedstuff 20 1) Properties of glycerol 21 2) Glycerol as energy source 22 3) Glycerol fermentation in rumen 25 4) Glycerol metabolism in ruminants 28 5) Effect of glycerol on carcass characteristics and sensory traits 30 4. References 33 CHAPTER THREE 43 Comparison of carcass and sensory traits, fatty acid profiles and volatile compounds among quality grades in longissimus dorsi and semimembranosus muscles of Korean cattle steers 43 1. Abstract 43 2. Introduction 45 3. Materials and methods 49 3.1. Animals and sampling 49 3.2. Proximate composition, cooking loss, shear force, pH, and color 53 3.3. Nucleotide content 53 3.4. Total and insoluble collagen contents 54 3.5. Free amino acids 55 3.6. Sensory evaluation 56 3.7. Fatty acid composition 57 3.8. Volatile compounds 58 3.9. Statistical analysis 60 4. Results and discussion 60 5. Conclusion 119 6. References 120 CHAPTER FOUR 127 Comparison of reducing sugar content, sensory traits, and fatty acids and volatile compound profiles of longissimus thoracis among Korean cattle, Holsteins, and Angus steers 127 1. Abstract 127 2. Introduction 128 3. Materials and methods 130 3.1. Beef sample preparation 130 3.2. Proximate composition, color, pH, shear force, and collagen content 133 3.3. Reducing sugars 133 3.4. Sensory evaluation 134 3.5. Fatty acid composition 135 3.6. Volatile compounds 136 3.7. Statistical analysis 137 4. Results and discussion 138 5. Conclusion 164 6. References 165 CHAPTER FIVE 169 Effects of dietary glycerin replacement on growth performance and rumen and carcass characteristics in Korean cattle steers 169 1. Abstract 169 2. Introduction 170 3. Materials and methods 173 3.1. Animals, housing, and diets 173 3.2. Blood, rumen fluid collections and measurements 177 3.3. Slaughter procedures and tissue sample collections 178 3.4. mRNA level in the liver 180 3.5. Chemical and physicochemical composition, color, pH, and shear force 181 3.6. Reducing sugar content 181 3.7. Sensory evaluation 181 3.8. Glycogen concentration 181 3.9. Fatty acid profile 182 3.10. Volatile compound 183 3.11. Statistical analysis 183 4. Results and discussion 184 5. Conclusion 208 6. References 209 CHAPTER SIX 215 Effect of dietary crude glycerin supplementation on growth performance, blood metabolites, ruminal fermentation parameters, and carcass characteristics in Korean cattle steers 215 1. Abstract 215 2. Introduction 216 3. Materials and methods 219 3.1. Animals, housing, and diets 219 3.2. Blood, rumen fluid collections and measurements 222 3.3. Slaughter procedures and tissue sample collections 223 3.4. mRNA level in the liver 225 3.5. Chemical and physicochemical compositions, color, pH, shear force, and water holding capacity 225 3.6. Reducing sugar content 226 3.7. Sensory evaluation 226 3.8. Glycogen concentration 226 3.9. Statistical analysis 226 4. Results and discussion 227 5. Conclusion 248 6. References 249 CHAPTER SEVEN 254 General conclusion 254 SUMMARY IN KOREAN 259Docto

Microbiology aetioloty of halitosis

학위논문 (석사)-- 서울대학교 대학원 : 치의학과, 2011.2. 김영구.Maste

측두하악장애 통증 환자의 통증 기원 및 외상 병력에 따른 임상적 특징에 관한 연구

학위논문 (석사)-- 서울대학교 대학원 : 치의학과 구강내과·진단학 전공, 2016. 2. 정진우.Temporomandibular disorder(TMD) is a multifactorial disease with chronic pain that was related with physical and psychological symptoms. Pain is the most common TMD symptom and showed different psychosocial and clinical patterns depending on the origin in the previous studies. Trauma on the orofacial or neck region potentially lead to increase severity and frequency of tempormandibular joint pain and to aggravate psychological factors. The aims of this study were to compare the differences in the clinical pain and psychological condition between the patients with and without history of trauma on the orofacial or neck region, and among the myogenous, arthrogenous, and mixed pain origin of TMD pain patients. A total of 1052 patients (mean age 34.4±15.7 years, 791 women and 261 men) with TMD who visited the Orofacial Pain Clinic of Seoul National University Dental Hospital were evaluated. Patients were divided into trauma and non-trauma groups according to the history of trauma in the orofacial or neck region, and the patients with TMD pain were categorized into three groups (Myogenous, Arthrogenous, and Mixed) according to the pain origin based on the RDC/TMD axis I diagnostic guidelines. Each patient was evaluated the clinical characteristics according to the RDC / TMD axis I and axis II questionnaires. The psychological characteristics were evaluated by the Symptom Checklist-90-R (SCL-90-R). The obtained results were as follows: 1. There were no significant differences in age and gender among the TMD pain groups and between trauma and non-trauma groups. 2. Myogenous pain group showed significantly higher SOM, GSI, PSDI, and PST scores than arthrogenous pain group. Mixed pain group showed significantly higher SOM, I-S, DEP, ANX, HOS, PHOB, PAR, PSY, GSI, PSDI, and PST scores than arthogenous pain group. 3. Trauma group has significantly higher SOM, ANX, PSY, GSI, PSDI, and PST scores than non-trauma group. 4. Mixed pain group showed significantly higher intensity of pain than two other groups and the percentage of high disability group in GCPS was higher in the order to mixed pain group, myogenous pain group, arthrogenous pain group. 5. Trauma group showed significantly higher intensity of pain and higher percentage of high disability group. There were no significant differences in duration of pain among the each group. 6. Arthogenous pain group showed lowest prevalence of headache, subjective insomnia, and tinnitus among the TMD pain groups. Myogenous pain group had highest prevalence of sleep bruxism. 7. Trauma group showed significant high prevalence of headache than non-trauma group. There were no significant differences in the prevalence of subjective insomnia, sleep bruxism, and tinnitus between non-trauma and trauma groups. 8. Patients who had both myogenous origin and history of trauma showed highest scores in the most SCL-90-R dimensions among the groups. Trauma history and pain origin could affect the clinical symptoms and psychological characteristics of patients with TMD pain and should be considered for the establishment of treatment.Ⅰ. INTRODUCTION 1 Ⅱ. MATERIALS AND METHODS 2 1. Subjects 2 2. Evaluation of psychological characteristics 3 3. Evaluation of Clinical pan characteristics and contributing factors 4 Ⅲ. RESULTS 4 1. Evaluation of psychological characteristics 5 2. Evaluation of clinical pan characteristics and contributing factors 5 3. Comparison of pain intensity, pain duration, and psychological profiles among groups combined with pain origin subtypes and trauma history 5 Ⅳ. DISCUSSION 6 Ⅴ. CONCLUSIONS 8 Ⅵ. REFERENCES 9 TABLES 12 KOREAN ABSTRACT 23Maste

Effects of synchronization of carbohydrate and protein supply in total mixed ration with Korean rice wine residue on ruminal fermentation, nitrogen metabolism and microbial protein synthesis in holstein steers

학위논문 (석사)-- 서울대학교 대학원 : 농생명공학부, 2011.8. 하종규.Maste

The effect of proton pump inhibitor on endoscopic finding of larynx and esophagus in patients with laryngopharygeal reflux symptom

학위논문 (석사)-- 서울대학교 대학원 : 의학과(이비인후과전공), 2013. 8. 이철희.서론: 인후두역류증은 이비인후과 영역에서 흔한 질환으로 최근 병태생리를 이해하는데 위-식도 역류에 주목하고 있다. 인후두 역류증 환자에서 후두 및 식도에 대한 내시경적 소견이 양성자 펌프 억제제를 사용한 후 어떻게 변하는지 확인하고 증상과 어떤 관련성을 보이는지 연구하였다. 방법: 2012년 10월부터 2013년 3월까지 인후두역류증으로 이비인후과를 내원한 환자 36명을 대상으로 이루어졌다. 내원 시 설문지를 통한 역류 증상 점수와 후두 내시경을 통한 역류 소견 지수를 얻었다. 경비식도내시경 검사를 통해 위식도역류 여부를 확인하고 Los Angeles 분류에 따라 역류성 식도염을 분류하였다. 양성자 펌프 억제제를 2개월간 복용한 후 설문지, 후두 내시경, 경비강 식도내시경을 시행하여 치료 전과 동일한 방법으로 자료를 얻었다. 결과: 총 36명의 환자 중 2개월 후 검사를 종료한 22명을 대상으로 분석하였다. 평균 연령은 52.8세이었으며, 남자는 4명, 여자는 18명이었다. 주된 증상은 경부 이물감이었다. 치료 전에 비해 치료 후 인후두 역류 증상, 역류 소견 지수와 역류성 식도염의 소견의 호전율은 각각 50%, 45%, 27%이었으며, 증상 및 후두 소견은 통계적으로 유의하게 호전되었다(p=0.003, 0.018). 그러나 역류 증상의 호전 여부, 역류 소견의 호전 여부, 역류성 식도염의 호전 여부 사이에는 상관관계가 보이지 않았다. 역류 증상의 호전이 된 11명 중에 4명은 후두 및 인두의 내시경적인 변화를 보이지 않았다. 결론: 인후두 역류증에서 양성자 펌프 억제제가 증상 호전에 도움을 주지만, 후두 및 식도의 내시경적 소견의 호전과 연관성을 보이지 않는다.Introduction: layrngopharyngeal reflux(LPR) is a common disorder. The mechanism of LRP is not clear until now. Here, we evaluated the endoscopic findings of larynx and esophagus after proton pump inhibitor(PPI), and analyzed the relationship with patients symptom. Methods: The 36 patients who complained of LPR symptom were enrolled. The reflux symptom, larynx finding and esophageal finding were assessed by reflux symptom index, reflux finding score and Los angeles classification, respectively. The data were collected at pre-treatment and 2 month after PPI treatment. Results:. Of the 36 patients with LPR, the 22 patients who finished all examinations were analyzed. Mean age was 52.8 years and 4 patients were male. The most common symptom was foreign body sensation on throat. The symptom, laryngeal finding and esophageal finding were improved significantly at 2 months after PPI treatment. There was no correlation between symptom, laryngeal finding and esophageal finding. Of patients whose symptom improved, the laryngeal and esophageal finding did not improve. Conclusions: Although symptom, laryngeal finding and esophageal finding may be improved after PPI treatment, the improvement of symptom may not correlate the improvement of endoscopic finding of larynx and esophagus.초록 i 목차 iii 표 및 그림 목록 iv 서론 1 대상환자 및 방법 3 결과 11 고찰 21 결론 24 참고문헌 25 초록 (영문) 28Maste

Review On Weak Convergence of Diffusion Processes Generated by Energy Forms

학위논문 (석사)-- 서울대학교 대학원 : 수리과학부, 2014. 2. Gerald Trutnau.We prove weak convergence of a sequence of stationary measures associated with Dirichlet forms using Mosco-convergence and Prokhorov's theorem. We explain explicitly the details in Uemura's paper, [5] 『On Weak Convergence of Diffusion Processes Generated by Energy Forms (1995)』.Abstract 1 Introduction 2 Statement of Theorem 3 Conservativeness and Tightness 4 Mosco-Convergence 5 Theorem 7 of Albeverio-Hegh-Krohn-Streit, [1] 6 Proof of Main Theorem 7 An Example References 국문 초록Maste

Ti-V-O 산화물의 상변화에서 하소분위기및 온도의 영향

Ti1-xVxO2 oxides were produced by a coprecipitation process using TiCl4 and VOCl3 as starting materials. As-precipitated gels were calcined at 500~800°C, either in a vacuum or oxygen atmosphere. Effects of the calcination atmosphere and temperature on the phase transition of crystalline Ti-V-O oxides were studied. Calcination in an oxygen atmosphere produced Ti-V-O oxides, which are mixtures of TiO2 and V2O5 oxides formed for all the calcination temperatures. Calcinations at 800°C in vacuum resulted in the formation of a rutile Ti1-xVxO2 single phase for all compositions of vanadium. A significant portion of vanadium ions is incorporated into the TiO2 lattice, which consistently decreases the lattice parameters of the rutile Ti1-xVxO2 phase as the vanadium addition increases