Clinical Impact of Exosomal microRNA as a Novel Biomarker of Liver Fibrosis

( Young Chang ),( Jae-a Han ),( Suk Min Kang ),( Soung Won Jeong ),( Tom Ryu ),( Han Seul Park ),( Jeong-ju Yoo ),( Sae Hwan Lee ),( Sang Gyune Kim ),( Young Seok Kim ),( Hong Soo Kim ),( So Young Jin 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1

Aims: Many approaches have been suggested for the non-invasive diagnosis of liver fibrosis, including the use of serum biomarkers and ultrasound-based elastography, but none has yet replaced liver biopsy. MicroRNAs (miRNAs) have been suggested as potential diagnostic tools for liver diseases. We investigated alterations in the expression of serum exosomal miRNAs with the progression of liver fibrosis and evaluated their clinical applicability as biomarkers. Methods: This study prospectively enrolled 71 patients who underwent liver biopsy at a large-volume academic hospital in Korea. Exosomes were extracted from serum samples, and next-generation sequencing (NGS) of miRNAs was conducted in patients from different stages of liver fibrosis. Differential expression of miRNAs was quantified using targeted real-time quantitative polymerase chain reaction (RT-qPCR). A model was derived to discriminate advanced fibrosis based on miRNA levels using multivariate logistic regression. The performance of this model was evaluated and compared using area under the receiver operator characteristic (ROC) curve (AUC) and De- Long’s test. Results: NGS data revealed the relationship between exosomal miR-122 expression and liver fibrosis progression. The level of miR-122 decreased as the pathologic fibrosis grade progressed from stage 0 to 4. Patients with biopsy-proven advanced fibrosis had significantly lower levels of exosomal miR-122 (P<0.001) than those without advanced fibrosis. Exosomal miR-122 exhibited a fair performance in discriminating advanced fibrosis with an AUC of 0.77, which improved to 0.86 in combination with fibrosis-4 score (FIB-4) and transient elastography (TE). This value was higher than that reported for any other non-invasive modalities, including TE (AUC of 0.80) or FIB-4 (AUC of 0.57) alone. In a subgroup of patients with a non-viral etiology of liver disease, the performance of exosomal miR-122 as a biomarker improved, evident from the increase in the AUC value to 0.87. In this subpopulation, the combination model of miR- 122, FIB-4, and TE showed the best discrimination ability (AUC of 0.90), which was significantly higher than that of TE alone (AUC of 0.83; DeLong’s test P=0.046). Inhibition of miR-122 expression increased the proliferation of the human hepatic stellate cell line, LX-2, and upregulated the expression of collagen- 1A, a-smooth muscle actin, fibronectin, and transforming growth factor-ß. Conclusions: Exosomal miR-122 may serve as a novel biomarker for discriminating advanced liver fibrosis, and its accuracy may enhanced in combination with other non-invasive tests such as FIB-4 and TE.

3-D 동작 분석 장치를 이용한 한국성인(20대, 30대)의 동작 범위에 관한 연구

임현균,김진호,박수찬,류신아,이영신 한국운동역학회 1998 한국운동역학회지 Vol.8 No.2

Devices, such as a goniometer, have been used to measure a human being's active range of motion, but interferences between subjects and testers have affected the result precision. In this study, 56 dynamic motion ranges were measured using a 3-D motion analysis system which is quite accurate (2mm error for 1m). The 3-D motion analysis system consists of VICON 140, data acquisition system, and data analysis program (KRISSMAS). 80 Korean subjects (40 males, 28±6.1 aged and 40 females, 28.4±6.9 aged) participated. Subjects were divided into 4 groups by Ro¨hrer's index based on National Anthropometric Survey of Korea 1997. Basic statistical analysis were performed using SPSS (ver. 8.0) programs after refining data. Various comparisons were performed for the right and left side, male and female, age groups (20's, 30's. and 40's-60's) using previous studies. The results show that female subjects have more flexible joints in the neck, hip, ankle, and wrist, while male subjects have more flexibility in their waist. But most of the significances were not high (>0.05). The prediction that the right side of Korean bodies would be mort flexible was not a good hypothesis. And the joints flexibilities are not correlated with Ro¨hrer's Index.

시ᆞ도 건강가정지원센터의 운영모형 개발 연구 : 역할 및 조직을 중심으로 It's Roles and Organization

장진경,오제은,한은주,류진아,원소연 한국가족관계학회 2006 한국가족관계학회지 Vol.11 No.1

건강가정지원센터 가정생활교육 프로그램 운영 및 성과 : 용산구·숙명여자대학교 시범사업을 중심으로

김명자,계선자,박미석,장진경,김연화,한은주,류진아 한국가족관계학회 2005 한국가족관계학회지 Vol.10 No.1

The purpose of this study is to propose a model for service programs and management strategies for the division of family education in Healthy Families Center. For the purpose, the researchers find out demands for the family education programs of people in Yong-San Gu, Seoul, exam the effect of each family education program of Yong-San Gu & Sookmyung Women's University Healthy Families Center from June to December, 2004. According to the results, people in Yong-San Gu need economic education service mostly, and they want to study at Saturday afternoon. The programs show positive effect on the improvement of family health.

Optimal expression and characterization of a fusion enzyme having dextransucrase and dextranase activities

Ryu, H.J.,Jin, X.,Lee, J.H.,Woo, H.J.,Kim, Y.M.,Kim, G.J.,Seo, E.S.,Kang, H.K.,Kim, J.,Cho, D.L.,Kimura, A.,Kim, D. IPC Science and Technology Press ; Elsevier Scienc 2010 Enzyme and microbial technology Vol.47 No.5

Long isomalto-oligosaccharides (IMOs) were generated via an engineered fusion enzyme of dextransucrase and dextranase (DSXR). To increase the expression level, response surface methodology (RSM) was utilized for optimization of protein expression conditions for enhancement of protein production by the effects of three-level-three-factors and their mutual interaction in Escherichia coli. Seventeen experiments were designed and conducted for investigation of cell density to start induction, induction temperature, and induction time. Optimal induction conditions included a cell density to start induction (A<SUB>600</SUB>) of 0.76 at 12.16<SUP>o</SUP>C for 18h for dextransucrase activity and a cell density to start induction (A<SUB>600</SUB>) of 0.75 at 10.5<SUP>o</SUP>C for 20.9h for dextranase activity. The produced dextransucrase or dextranase activity was obtained at 120.1+/-7.2 or 871+/-58U, respectively, from 1L cultures.

자기 방어적 소외와 공포

류아진(Ryu A-jin) 글로컬창의산업연구센터 2014 글로컬창의문화연구 Vol.- No.4

본 논문은 2005년 류승완 감독이 제작한 인권영화 <남자니까 아시잖아요>를 통해 현대 한국사회 성역할의 이중성에 대해 소외의 개념을 중심으로 분석하는 데 연구목표를 둔다. 이 영화에서 전형적인 가부장적 사상을 가진 주인공 우식은 사회로부터 부여된 ‘남성성’이란 성역할의 압박을 극복하지 못한 인물이며, 사회의 다양성을 내포한 인간 군상인 ‘포장마차’ 속 등장인물들과 여러 방면의 외적 갈등을 겪는다. 그로 인해 성역할 기대 충족을 위한 그의 투쟁, 우위 계층 선점의 명분이 무가치성으로 추락할 위기가 대두되자 그 불안은 곧 공포로 치환되고 자아를 보호하기 위해 방어적으로 타인에게서 자신을 분리시켜 의도적인 소외현상을 일으키게 된다. 이 소외의 표현은 우식의 타인에 대한 일방적인 비난의 형식으로 나타나며, 그 반동으로 타인과 자신은 다르다는 사실을 이용하여 자신의 존재 가치를 재차 확인?강조한다. 본고에서는 주인공을 통해 사회가 부여하는 성역할의 개념이 과연 무엇인지, 편견의 딜레마와 결말이 시사하는 한계가 무엇인지 현대 한국이라는 특정한 시간적·공간적 배경을 토대로 이를 고찰해보았다. The purpose of this paper is to analyze focusing on alienation about modern society of Korea and duality of gender roles through Human Rights Film <Hey Man> directed by Seung-wan Ryu. In the movie, The main character ‘Woo-sik’ who has typical patriarchal ideology is unable to overcome the pressure of gender roles granted by society and in conflict with various people in ‘street vendor’ signifying a different human character in the society of Korea. When his struggle for gender role expectations met and justification of the upper hierarchy preemption was facing with crisis of worthlessness, that anxiety turned into the fear. To protect his ego, he separated from others defensively, is lead to the intentional alienation phenomenon. The expression of the character’s alienation for others appeared in the form of a one-sided condemnation, he reaffirmed and emphasized his existence value taking advantage of the truth different from others. This paper analyzed what is the concept of gender roles granted by society through the main character and what is the suggested limit about movie ending and dilemma of prejudice. This is based on the time and space background about modern society of Korea.

The Influence of Feed Energy Density and a Formulated Additive on Rumen and Rectal Temperature in Hanwoo Steers

Cho, Sangbuem,Mbiriri, David Tinotenda,Shim, Kwanseob,Lee, A-Leum,Oh, Seong-Jin,Yang, Jinho,Ryu, Chaehwa,Kim, Young-Hoon,Seo, Kang-Seok,Chae, Jung-Il,Oh, Young Kyoon,Choi, Nag-Jin Asian Australasian Association of Animal Productio 2014 Animal Bioscience Vol.27 No.11

The present study investigated the optimum blending condition of protected fat, choline and yeast culture for lowering of rumen temperature. The Box Benken experimental design, a fractional factorial arrangement, and response surface methodology were employed. The optimum blending condition was determined using the rumen simulated in vitro fermentation. An additive formulated on the optimum condition contained 50% of protected fat, 25% of yeast culture, 5% of choline, 7% of organic zinc, 6.5% of cinnamon, and 6.5% of stevioside. The feed additive was supplemented at a rate of 0.1% of diet (orchard grass:concentrate, 3:7) and compared with a control which had no additive. The treatment resulted in lower volatile fatty acid (VFA) concentration and biogas than the control. To investigate the effect of the optimized additive and feed energy levels on rumen and rectal temperatures, four rumen cannulated Hanwoo (Korean native beef breed) steers were in a $4{\times}4$ Latin square design. Energy levels were varied to low and high by altering the ratio of forage to concentrate in diet: low energy (6:4) and high energy (4:6). The additive was added at a rate of 0.1% of the diet. The following parameters were measured; feed intake, rumen and rectal temperatures, ruminal pH and VFA concentration. This study was conducted in an environmentally controlled house with temperature set at $30^{\circ}C$ and relative humidity levels of 70%. Steers were housed individually in raised crates to facilitate collection of urine and feces. The adaptation period was for 14 days, 2 days for sampling and 7 days for resting the animals. The additive significantly reduced both rumen (p<0.01) and rectal temperatures (p<0.001) without depressed feed intake. There were interactions (p<0.01) between energy level and additive on ruminal temperature. Neither additive nor energy level had an effect on total VFA concentration. The additive however, significantly increased (p<0.01) propionate and subsequently had lower acetate:propionate (A/P) ratios than non-additive supplementation. High concentrate diets had significantly lower pH. Interactions between energy and additive were observed (p<0.01) in ammonia nitrogen production. Supplementation of diets with the additive resulted in lower rumen and rectal temperatures, hence the additive showed promise in alleviating undesirable effects of heat stress in cattle.

ALS/FTLD-linked TDP-43 regulates neurite morphology and cell survival in differentiated neurons

Han, Jeong-Ho,Yu, Tae-Hoon,Ryu, Hyun-Hee,Jun, Mi-Hee,Ban, Byung-Kwan,Jang, Deok-Jin,Lee, Jin-A Elsevier 2013 Experimental cell research Vol.319 No.13

<P><B>Abstract</B></P> <P>Tar-DNA binding protein of 43kDa (TDP-43) has been characterized as a major component of protein aggregates in brains with neurodegenerative diseases such as frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS). However, physiological roles of TDP-43 and early cellular pathogenic effects caused by disease associated mutations in differentiated neurons are still largely unknown. Here, we investigated the physiological roles of TDP-43 and the effects of missense mutations associated with diseases in differentiated cortical neurons. The reduction of TDP-43 by siRNA increased abnormal neurites and decreased cell viability. ALS/FTLD-associated missense mutant proteins (A315T, Q331K, and M337V) were partially mislocalized to the cytosol and neurites when compared to wild-type and showed abnormal neurites similar to those observed in cases of loss of TDP-43. Interestingly, cytosolic expression of wild-type TDP-43 with mutated nuclear localization signals also induced abnormal neurtie morphology and reduction of cell viability. However, there was no significant difference in the effects of cytosolic expression in neuronal morphology and cell toxicity between wild-type and missense mutant proteins. Thus, our results suggest that mislocalization of missense mutant TDP-43 may contribute to loss of TDP-43 function and affect neuronal morphology, probably via dominant negative action before severe neurodegeneration in differentiated cortical neurons.</P> <P><B>Highlights</B></P> <P> <UL> <LI> The function of nuclear TDP-43 in neurite morphology in mature neurons. </LI> <LI> Partial mislocalization of TDP-43 missense mutants into cytosol from nucleus. </LI> <LI> Abnormal neurite morphology caused by missense mutants of TDP-43. </LI> <LI> The effect of cytosolic expression of TDP-43 in neurite morphology and in cell survival. </LI> </UL> </P>

행동 복제 강화학습 및 딥러닝 사물 부분 검출 기술에 기반한 사람형 로봇손의 사물 조작

오지헌 ( Ji Heon Oh ),류가현 ( Ga Hyun Ryu ),박나현 ( Na Hyeon Park ),( Edwin Valarezo Añazco ),( Patricio Rivera Lopez ),원다슬 ( Da Seul Won ),정진균 ( Jin Gyun Jeong ),장윤정 ( Yun Jung Chang ),김태성 ( Tae-seong Kim ) 한국정보처리학회 2020 한국정보처리학회 학술대회논문집 Vol.27 No.2

최근 사람형(Anthropomorphic)로봇손의 사물조작 지능을 개발하기 위하여 행동복제(Behavior Cloning) Deep Reinforcement Learning(DRL) 연구가 진행중이다. 자유도(Degree of Freedom, DOF)가 높은 사람형 로봇손의 학습 문제점을 개선하기 위하여, 행동 복제를 통한 Human Demonstration Augmented(DA)강화 학습을 통하여 사람처럼 사물을 조작하는 지능을 학습시킬 수 있다. 그러나 사물 조작에 있어, 의미 있는 파지를 위해서는 사물의 특정 부위를 인식하고 파지하는 방법이 필수적이다. 본 연구에서는 딥러닝 YOLO 기술을 적용하여 사물의 특정 부위를 인식하고, DA-DRL 을 적용하여, 사물의 특정 부분을 파지하는 딥러닝 학습 기술을 제안하고, 2 종 사물(망치 및 칼)의 손잡이 부분을 인식하고 파지하여 검증한다. 본 연구에서 제안하는 학습방법은 사람과 상호작용하거나 도구를 용도에 맞게 사용해야하는 분야에서 유용할 것이다.

휴먼형 로봇 손의 사물 조작 수행을 이용한 인간 행동 복제 강화학습 정책 최적화 방법 성능 평가

박나현 ( Na Hyeon Park ),오지헌 ( Ji Heon Oh ),류가현 ( Ga Hyun Ryu ),( Edwin Valarezo Añazco ),( Patricio Rivera Lopez ),원다슬 ( Da Seul Won ),정진균 ( Jin Gyun Jeong ),장윤정 ( Yun Jung Chang ),김태성 ( Tae-seong Kim ) 한국정보처리학회 2020 한국정보처리학회 학술대회논문집 Vol.27 No.2

로봇이 사람과 같이 다양하고 복잡한 사물 조작을 하기 위해서 휴먼형 로봇손의 사물 파지 작업이 필수적이다. 자유도 (Degree of Freedom, DoF)가 높은 휴먼형(anthropomorphic) 로봇손을 학습시키기 위하여 사람 데모(human demonstration)가 결합된 강화학습 최적화 방법이 제안되었다. 본 연구에서는 강화학습 최적화 방법에 사람 데모가 결합된 Demonstration Augmented Natural Policy Gradient (DA-NPG)와 NPG 의 성능 비교를 통하여 행동 복제의 효율성을 확인하고, DA-NPG, DA-Trust Region Policy Optimization (DA-TRPO), DA-Proximal Policy Optimization (DA-PPO)의 최적화 방법의 성능 평가를 위하여 6 종의 물체에 대한 휴먼형 로봇손의 사물 조작 작업을 수행한다. 그 결과, DA-NPG 와 NPG를 비교한 결과를 통해 휴먼형 로봇손의 사물 조작 강화학습에 행동 복제가 효율적임을 증명하였다. 또한, DA-NPG 는 DA-TRPO 와 유사한 성능을 보이면서 모든 물체에 대한 사물 파지에 성공하여 가장 안정적이었다. 반면, DA-TRPO 와 DA-PPO 는 사물 조작에 실패한 물체가 존재하여 불안정한 성능을 보였다. 본 연구에서 제안하는 방법은 향후 실제 휴먼형 로봇에 적용하여 휴먼형 로봇 손의 사물조작 지능 개발에 유용할 것으로 전망된다.