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A Study of Microsatellite Instability in Primary Small Cell Lung Cancers by Microsatellite Analysis (원발성 소세포폐암에서 Microsatellite 분석을 이용한 Microsatellite 불안정화에 대한 연구)

  • Cho, Eun-Song;Chang, Joon;Park, Jae-Min;Shin, Dong-Hwan;Kim, Se-Hoon;Kim, Young-Sam;Chang, Yoon-Soo;Cho, Chul-Ho;Kwak, Seung-Min;Lee, Jun-Gu;Chung, Kyung-Young;Kim, Sung-Kyu;Lee, Won-Young;Kim, Se-Kyu
    • Tuberculosis and Respiratory Diseases
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    • v.48 no.2
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    • pp.180-190
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    • 2000
  • Background: Genomic instability, which is manifested by the replication error(RER) phenotype, has been proposed for the promotion of genetic alterations necessary for carcinogenesis. Merlo et al. reported frequent microsatellite instability in primary small cell lung cancers. However, Kim et al. found that instability occurred in only 1% of the loci tested and did not resemble the replication error-positive phenotype. The significance of microsatellite instability in the tumorigenesis of small cell lung cancer as well as the relationship between microsatellite instability and its clinical prognosis was investigated in our study. Methods: Fifteen primary small cell lung cancers were chosen for this study. The DNAs extracted from paraffin-embedded tissue blocks with primary tumor and corresponding control tissue were investigated. Forty microsatellite markers on chromosome 1p, 2p, 3p, 5q, 6p, 6q, 9p, 9q, 13q, and 17p were used in the microsatellite analysis. Results: Thirteen(86.7%) of 15 tumors exhibited LOH in at least one of the tested microsatellite markers. Three of 13 tumors exhibiting LOH lost a larger area in chromosome 9p. LOH was shown in 72.7% on chromosome 2p, 40% on 3p, 50% on 5q, 46.7% on 9p, 69.2% on 13q, and 66.7% on 17p(Table 1). Nine(60%) of 15 tumors exhibited shifted bands in at least one of the tested microsatellite markers. Nine cases exhibiting shifted bands showed altered loci ranging 2.5~52.5%(mean $9.4%\pm16.19$)(Table 2). Shifted bands occurred in 5.7% (34 of 600) of the loci tested(Table 2). Nine cases with shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 35 weeks. Six cases without shifted bands exhibited LOH ranging between 0~83.3%, and the median survival duration of those cases was 73 weeks. There was no significant difference between median survival durations of the two groups(p=0.4712). Conclusion: Microsatellite instability as well as the inactivation of several tumor suppressor genes may play important roles in the development and progression process of tumors. However, the relationship between microsatellite instability and its clinical prognosis in primary small cell lung cancer could not be established.

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Expression of Decidual Natural Killer (NK) Cells in Women of Recurrent Abortion with Increased Peripheral NK Cells (말초혈액자연살해세포가 증가된 반복유산 환자의 탈락막자연살해세포의 발현)

  • Yeon, Myeong-Jin;Yang, Kwang-Moon;Park, Chan-Woo;Song, In-Ok;Kang, Inn-Soo;Hong, Sung-Ran;Cho, Dong-Hee;Cho, Yong-Kyoon
    • Clinical and Experimental Reproductive Medicine
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    • v.35 no.2
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    • pp.119-129
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    • 2008
  • Objective: The purpose of this study was to quantify decidual $CD56^+$ and $CD16^+$ NK cell subtype population and to evaluate the correlation between decidual NK cell expression and peripheral $CD56^+$ NK cell expression in women with a history of recurrent abortion and increased peripheral NK cells. Methods: Twenty-nine women with recurrent abortion and elevated peripheral $CD56^+$ NK cell percentage who had chromosomally normal conceptus were included in this study. Thirty-two women with recurrent abortion who had chromosomally abnormal conceptus were used as controls. Distribution of $CD56^+$ and $CD16^+$ NK cells in decidual tissues including implantation sites was examined by immunohistochemical staining. The degree of immunohistochemical staining was interpreted by score and percentage. Results: There was a significant difference in decidual $CD56^+$ NK cell score ($43.6{\pm}24.5$ vs. $23.9{\pm}16.3$ P =0.001) and $CD56^+$ NK cell percentage ($42.1{\pm}11.7$ vs. $33.9{\pm}15.8$ P =0.027) between increased peripheral NK cell group and control group. However, there was no statistically significant difference in decidual $CD16^+$ NK cell score ($18.7{\pm}9.5$ vs. $13.2{\pm}39.4$ P =0.108) and $CD16^+$ NK cell percentage ($24.7{\pm}5.9$ vs. $23.4{\pm}11.7$ P =0.599). There was no significant correlation between decidual NK cell score and peripheral NK cell percentage in increase peripheral NK cell group (peripheral $CD56^+$ NK cell percentage vs. decidual $CD56^+$ NK cell score, r=-0.016, P =0.932, peripheral $CD16^+$ NK cell percentage vs. decidual $CD16^+$ NK cell score, r=0.008, P =0.968). Conclusion: This study shows that $CD56^+$ decidual NK cells are increased in decidua of women exhibiting a history of recurrent abortion with increased $CD56^+$ peripheral NK cell. There was no significant correlation between decidual and peripheral NK cell increment in increase peripheral NK cell group. This study suggests the possibility that decidual NK cells may play an important role in the immune mechanism of recurrent abortion.

The Effect of Heat Shock Response on the Tumor Necrosis Factor-$\alpha$-induced Acute Lung Injury in Rats (Tumor Necrosis Factor-$\alpha$로 유도되는 백서의 급성 폐손상에 열충격반응이 미치는 효과)

  • Koh, Youn-Suck;Lim, Chae-Man;Kim, Mi-Jung;Cho, Won-Kyung;Jeoung, Byung-O;Song, Kyu-Young;Shim, Tae-Sun;Lee, Sang-Do;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong
    • Tuberculosis and Respiratory Diseases
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    • v.44 no.6
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    • pp.1343-1352
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    • 1997
  • Background : Heat-treated cells are known to be protected from lysis by TNF, which is considered to play a central role in the pathogenesis of sepsis-induced acute lung injury. The objective of the study was to investigate the effect of heat shock response by heat-pretreatment on the acute lung injury of the rats induced by intratracheally administered TNF-$\alpha$, Methods : We intratracheally instilled either saline or TNF (R&D, 500ng) with and without heat pretreatment in Sprague-Dawley rats weighing 250~350 g. The heated rats were raised their rectal temperature to $41^{\circ}C$ and was maintained thereafter for 13 minutes at 18 h before intratracheal administration of saline or TNF. After 5 h of intratracheal treatment, lung leak, lung myeloperoxidase activity (MPO) and heat shock proteins were measured in rats. Lung leak index was defined as counts per minute of $I^{25}$ in the right lung divided by counts per minutes of $I^{25}$ in 1.0 ml of blood. All data are expressed as means ${\pm}$SE. Results : There is no difference in acute lung leak index ($0.099{\pm}0.024$ vs $0.123{\pm}0.005$) among the rats given saline intratracheally with and without heat pretreatment, but MPO activity showed a decreased tendency in heat-pretreated rats ($4.58{\pm}0.79\;U/g$) compared with heat-unpretreated rats ($7.32{\pm}0.97\;U/g$) (P=0.064). Rats administered TNF intratracheally with heat-pretreatment had decreased lung leak index ($0.137{\pm}0.012$) and lung MPO activity ($5.51{\pm}1.04\;U/g$) compared with those of heat-unpretreated and TNF-administered rats ($0.186{\pm}0.016$, $14.34{\pm}1.22\;U/g$) (P<0.05 in each). There were no significant difference of lung leak index and MPO activity between TNF-treated rats with heat-pretreatment and saline-treated rats with and without heat-pretreatment. Conclusion : The heat shock response attenuated neutrophil recruitment and acute lung leak induced by intratracheal instillation of TNF-in rats.

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A Study of Guidelines for Genetic Counseling in Preimplantation Genetic Diagnosis (PGD) (착상전 유전진단을 위한 유전상담 현황과 지침개발을 위한 기초 연구)

  • Kim, Min-Jee;Lee, Hyoung-Song;Kang, Inn-Soo;Jeong, Seon-Yong;Kim, Hyon-J.
    • Journal of Genetic Medicine
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    • v.7 no.2
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    • pp.125-132
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    • 2010
  • Purpose: Preimplantation genetic diagnosis (PGD), also known as embryo screening, is a pre-pregnancy technique used to identify genetic defects in embryos created through in vitro fertilization. PGD is considered a means of prenatal diagnosis of genetic abnormalities. PGD is used when one or both genetic parents has a known genetic abnormality; testing is performed on an embryo to determine if it also carries the genetic abnormality. The main advantage of PGD is the avoidance of selective pregnancy termination as it imparts a high likelihood that the baby will be free of the disease under consideration. The application of PGD to genetic practices, reproductive medicine, and genetic counseling is becoming the key component of fertility practice because of the need to develop a custom PGD design for each couple. Materials and Methods: In this study, a survey on the contents of genetic counseling in PGD was carried out via direct contact or e-mail with the patients and specialists who had experienced PGD during the three months from February to April 2010. Results: A total of 91 persons including 60 patients, 49 of whom had a chromosomal disorder and 11 of whom had a single gene disorder, and 31 PGD specialists responded to the survey. Analysis of the survey results revealed that all respondents were well aware of the importance of genetic counseling in all steps of PGD including planning, operation, and follow-up. The patient group responded that the possibility of unexpected results (51.7%), genetic risk assessment and recurrence risk (46.7%), the reproduction options (46.7%), the procedure and limitation of PGD (43.3%) and the information of PGD technology (35.0%) should be included as a genetic counseling information. In detail, 51.7% of patients wanted to be counseled for the possibility of unexpected results and the recurrence risk, while 46.7% wanted to know their reproduction options (46.7%). Approximately 96.7% of specialists replied that a non-M.D. genetic counselor is necessary for effective and systematic genetic counseling in PGD because it is difficult for physicians to offer satisfying information to patients due to lack of counseling time and specific knowledge of the disorders. Conclusions: The information from the survey provides important insight into the overall present situation of genetic counseling for PGD in Korea. The survey results demonstrated that there is a general awareness that genetic counseling is essential for PGD, suggesting that appropriate genetic counseling may play a important role in the success of PGD. The establishment of genetic counseling guidelines for PGD may contribute to better planning and management strategies for PGD.

The Characteristics and Significance of 'Wanpan Changgeuk' Written by Heogyu (허규 연출 '완판 창극'의 특징과 의의)

  • Kim, Kee-hyung
    • (The) Research of the performance art and culture
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    • no.20
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    • pp.5-30
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    • 2010
  • It has been diversified and serious attempt to establish the identity of Changgeuk, but it is still independent dramaturgy or the current unformed progressive art. In this situation, exploring works of the identity of changgeuk that is base on the performed individual and specific works in the title of Changgeuk is needed. The 80s and 90s Heo, Gyu was leading an active life as a director who was responsible for directing of Changgeuk. He dramatized Siljeon Pansori -which is a group of Pansori missing text- as well as 5-remained Songs in Pansori and he presented a number of creative Changgeuk works on stage. Especially, the completion of dramatizing 5-remained Songs in Pansori under the name of 'Wanpan Changgeuk -which means full version performance without omit-' is the one of his big achievement by performing "Heungbojeon" on the stage 1982 and "Jeokbyeokga" 1985. The purposes of this research are confirmation of Heo's direction of the formulation and considering its characteristics & significance through 'Wanpan Changgeuk' which written by Heo. Heo was a practical play who was interested in the subjective formulation of national culture and creative transmission for Korean traditional performance. He tried to formulate Changgeuk to a representative performance of Korea. In the process he pointed out those problems, (1) interpretation of a work problem, (2) actor's creative problems, (3) structure problem of theater for Changgeuk. He indicated that the other challenges are to use of the stage & device, to overcome sentimentalism, to stylize acting, to improve own quality, to control the speed and length of the song, to choose the suitable musical accompaniment, to create new repertories problems, and etc. Changgeuk is classified in 3 group by origin, (1)dramatizing of 5-remained Songs, (2)dramatizing of 7-missing Songs, (3)creative dramatizing. It contains all of 3 types that Heo's work. The dramatizing of remained 5 Songs are the great importance among those works. Heo hoped that Chaggeuk has become the most representative art work of Korea by performing 'Wanpan Changgeuk' compiled heritage of Korea's outstanding artistic achievement. The characteristics of 'Wanpan Changgeuk' can be summarized following four. (1) Directing attitudes that emphasizes tradition, (2) Accepting the elements of traditional performance actively, (3) Valuing the classy and ethic, (4) Emphasizing humor and active utilizing of the secondary characters. Heo's 'Wanpan Changgeuk' shows a peak of the artistic level which Changgeuk can be reached. He want to make Changgeuk a Korean representative artistic performance by compiling Pansori heritage and accommodating Korean traditional performance. Heo continued his effort to present Pansori's authenticity and to dramatize from beginning to end without missing. It shows very well that 'Wanpan Changgeuk' takes 4~5 hours for playing. It looks Heo's achievement in the 'Wanpan Changgeuk' influenced Changgeuk significantly since then. Heo's 'Wanpan Changgeuk' is matrix of 'Wanpan JangMak Changgeuk' attempted in the 1990s. Especially, their intent is consistent to synthesize texts and to show all the virtue of Pansori. But 90's 'Wanpan JangMak Changgeuk' aim for large stage, fancy device & costume and variety contents compared with 'Wanpan Changgeuk'. Recently, producers have tried not to make a impressive Changgeuk but to make a interesting one. They usually organize performance within 2 hours and prefer orchestral music to its unique sound. In those point of view, it seems that Heo's idle in 'Wanpan Changgeuk' has become one of target to conquer in these days.

Thinking in Terms of East-West Contacts through Spreading Process of Sarmathia-Pattened Scabbard on Tillya-Tepe Site in Afghanistan (아프가니스탄 틸랴 테페의 사르마티아(Sarmathia)식 검집 패용 방식의 전개 과정으로 본 동서교섭)

  • Lee, Song Ran
    • Korean Journal of Heritage: History & Science
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    • v.45 no.4
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    • pp.54-73
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    • 2012
  • In this article, we examined the patterns of activities of the Sarmathians though in a humble measure, with a focus on the regions where the Sarmathian sheaths spreaded. One of the main weapons the mounted nomads like the Scythias, the Sarmathians, and the Alans used at war was a spear. Though complementary, a sword was the most convenient and appropriate weapon when fighting at a near distance, fallen from the horse to the ground. The Sarmathian swords continued the tradition of the Akinakes which the Scythias or the Persians used, but those of the Sarmathians showed some advances in terms of the easiness with which a sword was drawn out from a sheath, and the way the sheaths were worn to parts of a human body. It turns out that the Sarmathian sheaths, which were designed for the people to draw swords easily, having the sheaths attached to thighs through 4 bumps, spread extensively from Pazyryk, Altai, to South Siberia, Bactria, Parthia and Rome. The most noteworthy out of all the Sarmathian sheaths were the ones that were excavated from the 4th tomb in Tillatepe, Afghanistan which belonged to the region of Bactria. The owner of the fourth tomb of Tilla-tepe whose region was under the control of Kushan Dynasty at that time, was buried wearing Sarmathian swords, and regarded as a big shot in the region of Bactria which was also under the governance of Kushan Dynasty. The fact that the owner of the tomb wore two swords suggests that there had been active exchange between Bactria and Sarmathia. It seemed that the reason why the Sarmathians could play an important role in the exchange between the East and the West might have something to do with their role of supplying Chinese goods to Silk Road. That's why we are interested in how the copper mirrors of Han Dynasty, decoration beads like melon-type beads, crystal beads and goldring articulated beads, and the artifacts of South China which produced silks were excavated in the northern steppe route where the Sarmathians actively worked. Our study have established that the eye beads discovered in Sarmathian tomb estimated to have been built around the 1st century B.C. were reprocessed in China, and then imported to Sarmathia again. We should note the Huns as a medium between the Sarmathians and the South China which were far apart from each other. Thus gold-ring articulated beads which were spread out mainly across the South China has been discovered in the Huns' remains. On the other hand, between 2nd century B.C. and 2nd century A.D. which were main periods of the Sarmathians, it was considered that the traffic route connecting the steppe route and the South China might be West-South silk road which started from Yunnan, passed through Myanmar, Pakistan, and Afghanistan, and then went into the east of India. The West-south Silk road is presumed to have been used by nomadic tribes who wanted to get the goods from South China before the Oasis route was activated by the Han Dynasty's policy of managing the countries bordering on Western China.

6·25 Special Play Study (6·25 특집극 <최후의 증인> 연구)

  • Song, Chihyuk
    • (The) Research of the performance art and culture
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    • no.42
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    • pp.47-75
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    • 2021
  • This thesis looks into the interpretation of the Korean War and mystery genre in Korea in the 1970s by analyzing the special drama , in which the theme was directly related to the Korean War, airing through MBC in 1979. It begins by finding the change in direction in the 1970s when the world of TV was dictated through the heavy censorship and the memory of the war by the government. It also looks at the intentions of the producer who was taking in the new way and the viewers who also accepted this drama and its reflections. In order to gain some insights into these issues, it compares between the drama "The Last Witness" and the original novel by Seong-jong Kim who holds the same time to see the way in which this is dramatized. The drama, "The Last Witness", was produced with a plan to generate a high-quality special drama which combined both artistry and sense of purpose. Nevertheless, as watching TV became a leisurely past-time during this period, TV dramas become more aggressive and suggestive in order to attract viewers. This ultimately was encored with obstacles due to the regime and the heavy censorship at the time. The genre of special drama that is well known in South Korea, is designed as an art form to satisfy both their unique artistry and its purpose. The conflict is seen between the key elements of the artistic drama crated by the producers and the 'encouraged' elements that often are needed to engage the viewers. Thus, more often than not, special dramas defeat the original intention of national harmony, encouraged by the regime. This is due to the 'novelty' aspect which grows from the effort of bringing enjoyment to viewers whilst also trying to achieve the artistic drama to life. Alongside this, crime element in this drama is designed in a way that visually embodies the process of deduction, becoming a new possibility to secure the reality of the times. However, it was also a paradoxical existence since it was indicated as an example of unrefined culture that lost its original intention. In that way, it is worth to think that detective suspense stories, which were not popular in Korea, influenced viewers as a tv drama series in the 1970s through the various elements that compose the genre. They went through a process of transplantation and acceptance whilst also attempting to satisfy the viewers and their encouraged elements to engage them. As is well known, crime drama in Korea has its own style by mixing anticommunism and detective reasoning. This combination is found in the way in which the genre naturally forms through the elements selected and excluded in the dramatization of "The Last Witness". The point is that the special drama "The Last Witness" can be seen as an intermediate form that shows the tendency of transformation from the detective reasoning form alongside the crime aspects as TV dramas began to include anticommunism messaging and investigation in the 1970s. In conclusion, when the detective reasoning is used as an element in a TV drama, it shows the trust of the public system and it constantly seeks the possibility of circumventing the political interpretation. The memories of the war is seen as a tool that neutralizes the dismal imaginations inscribed on the dark side of society and the system. As a result, "The Last Witness", broadcasted at the end of the Yushin regime in Korea, is a strange result which combines the logic of a special drama and the encouraged characteristics of television dramas. The viewers' desire which is the discussion about the hidden traces from the texts needs to be restored again.

A Case Study(II) on Development and Application of 'Literature-Art-Science' Integrated Education Programs ('문학-미술-과학' 융합교육 프로그램의 개발 및 적용 사례 연구(II))

  • Choi, Byung Kil
    • Korea Science and Art Forum
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    • v.32
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    • pp.319-334
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    • 2018
  • This research is a case study to make sure the enhancement of students' imagination and creativity through developing and applying the Literature-Art-Science Integrated Education Program. Its research object was totally 25 persons of 29 students of the 1st to the 4 th Grades from Gunsan Sulsan Elementary School. Its research period lasted for 4 months from September to December, 2017, and I, as the research place, used the art room at Gunsan Sulsan Elementary School. The programs were totally 10 sessions with a unit of 1 session per each grade for 2 hours from 1:00 to 3:00 in the afternoon from Monday through Friday. I fixed ten themes of this program-eight plane modeling, and two solid modeling, and finished the work of storytelling during summer vacation. And I arranged their levels as low:middle:high(3:5:2) ones. The former was 'A Film of Monster Gorilla'(L), 'Learning the Spirit of Gyeongju Choi's Family'(M), 'A Tale of My Friend Made of Natural Materials'(L), 'The Reading of My Dream'(M), 'Gathering the Objects in My Mobile'(M), 'A Mock Trial of Marrying Off'(M), 'Painting My Favorite Children's Poem'(H), and 'Painting My Favorite Children's Song'(H), and the latter was 'Seeking for a Bluebird in My Mind'(L), and 'Making My Cherished Object' (M). Then I used the unique art expression technique per each theme, which were in sequence marbling, Korean paper art, combine painting, collage, imaginary painting, imaginary painting, play dough art, imaginary painting techniques. And I delivered to the students the scientific knowledge in terms of growing or manufacturing processes of materials used for making artworks. Prior to and after the processing this program, I surveyed about the students' ability of integrated thinking and emotional experience by 'Figure B Type' and 'Figure A Type' of The Torrance Tests of Creative Thinking, and took statistics with the resultant data. And I executed a paired t-test in order to verify the significance of mean difference in the result of investigation with those data. From the analyzed result according to the elements of creativity and the mean quotients of creativity, there showed a significant difference (t=3.47, p<.01) in 'fluency', and also a significant difference(t=3.59, p<.01) in 'creativity.' Judging from the statistic values of two fields such as the student's ability of integrated thinking and emotional experience, I estimate that over the majority of the students showed the enhancement in self-confident creative expression as well as higher interest and concern through this program. The result that I arranged and analyzed the making process of artworks, the photos of the resultant, etc. as such is as follows : Firstly, from this program being proceeded as art-centered STEAM class, the student's systematic problem-solving ability was improved in his ability of integrated thinking to transform the literary contents into artistic one. Secondly, the student obtained the emotional experience such as interest in the class, self-confidence, intellectual satisfaction, self-fulfillment, etc. through art-centered STEAM class using ten art expression techniques. Thirdly, the student's mind willing to cooperate, communicate with his friends, and care for them was ripened in the process of problem-solving. Fourth, the student's self-confidence was further instilled when presenting famous artists and their artworks in the introduction and finale of ten art expression techniques. Likewise, the statistic values on the fields of student's ability of integrated thinking and emotional experience illustrate that over the majority of the students showed improvement in the ability of creative expression with confidence as well as higher interest and concern upon this program.

The cinematic interpretation of pansori and its transformation process (판소리의 영화적 해석과 변모의 과정)

  • Song, So-ra
    • (The) Research of the performance art and culture
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    • no.43
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    • pp.47-78
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    • 2021
  • This study was written to examine the acceptance of pansori in movies based on pansori, and to explore changes in modern society's perception and expectations of pansori. A pansori is getting the love of the upper and lower castes in the late Joseon period, but loses the status at the time of the Japanese colonial rule and Korean War. In response, the country designated pansori as an important intangible cultural asset in 1964 to protect the disappearance of pansori. Until the 1980s, however, pansori did not gain popularity by itself. After the 2000s, Pansori tried to breathe in with the contemporary public due to the socio-cultural demand to globalize our culture. And now Pansori is one of the most popular cultures in the world today, as the pop band Feel the Rhythm of KOREA shows. The changing public perception of pansori and its status in modern society can also be seen in the mass media called movies. This study explored the process of this change with six films based on pansori, from "Seopyeonje" directed by Lim Kwon-taek in 1993 to the film "The Singer" in 2020. First, the films "Seopyeonje" and "Hwimori" were produced in the 1990s. Both of these films show the reality of pansori, which has fallen out of public interest due to the crisis of transmission in the early and mid-20th century. And in the midst of that, he captured the scene of a singer struggling fiercely for the artistic completion of Pansori itself. Next, look at the film "Lineage of the Voice" in 2008 and "DURESORI: The Voice of East" in 2012. These two films depict the growth of children who perform art, featuring contemporary children who play pansori and Korean traditional music. Pansori in these films is no longer an old piece of music, nor is it a sublime art that is completed in harsh training. It is only naturally treated as one of the contemporary arts. Finally, "The Sound of a Flower" in 2015 and "The Singer" in 2020. The two films constructed a story from Pansori's history based on the time background of the film during the late Joseon Dynasty, when Pansori was loved the most by the people. This reflects the atmosphere of the times when traditions are used as the subject of cultural content, and shows the changed public perception of pansori and the status of pansori.

Anti-inflammatory Effects of Pentoxifylline and Neutrophil Elastase Inhibitor on Lipopolysaccharide-Induced Acute Lung Injury In Vitro (In Vitro 내독소 유도성 급성 폐손상에서 Pentoxifylline과 Neutrophil Elastase Inhibitor의 항염효과)

  • Kim, Young-Kyoon;Kim, Seung-Joon;Park, Yong-Keun;Kim, Seok-Chan;Kim, Kwan-Hyoung;Moon, Hwa-Sik;Song, Jeong-Sup;Park, Sung-Hak;Kim, Sang-Ho
    • Tuberculosis and Respiratory Diseases
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    • v.49 no.6
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    • pp.691-702
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    • 2000
  • Background : Acute lung injury (ALI) is a commonly encountered respiratory disease and its prognosis is poor when the treatment is not provided promptly and properly. However no specific pharmacologic treatment is currently available for ALI, although recently several supportive drugs have been under scrutiny. We studied anti-inflammatory effects of pentoxifylline (PF), a methylated xanthine, and ONO-5046, a synthetic neutrophil elastase inhibitor on lipopolysaccharide (LPS)-induced ALI in vitro. Methods : To establish an in vitro model of LPS-induced ALI, primary rat alveolar macrophages and peripheral neutrophils in various ratios (1:0, 5:1, 1:1, 1:5, 0:1) were co-cultured with transformed rat alveolar epithelial cells (L2 cell line) or vascular endothelial cells (IP2-E4 cell line) under LPS stimulation. Each experiment was divided into five groups-control, LPS, LPS+PF, LPS+ONO, and LPS+PF+ONO. We compared LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils in various ratios, and the resultant cytotoxicity on L2 cells or IP2-E4 cells between groups. In addition we also compared the productions of tumor necrosis factor (TNF)-$\alpha$ interleukin (IL)-$1{\beta}$, monocyte chemotactic protein(MCP)-1, IL-6, and IL-10 as well as mRNA expressions of TNF-$\alpha$ inducible nitric oxide synthetase(iNOS), and MCP-1 from LPS-stimulated primary rat alveolar macrophages between groups. Results : (1) PF and ONO-5046 in each or both showed a trend to suppress LPS-induced superoxide anion productions from primary rat alveolar macrophages and peripheral neutrophils regardless of their ratio, except for the LPS+PF+ONO group with the 1:5 ratio, although statistical significance was limited to a few selected experimental conditions. (2) PF and ONO-5046 in each or both showed a trend to prevent IP2-E4 cells from LPS-induced cytotoxicity by primary rat alveolar macrophages and peripheral neutrophils regardless their ratio, although statistical significance was limited to a few selected experimental conditions. the effects of PF and/or ONO-5046 on LPS-induced L2 cell cytotoxicity varied according to experimental conditions. (3) PF showed a trend to inhibit LPS-induced productions of INF-$\alpha$ MCP-1, and IL-10 from primary rat alveolar macrophages. ONO-5046 alone didnot affect the LPS-induced productions of proinflammatory cytokines from primary rat alveolar macrophages but the combination of PF and ONO-5046 showed a trend to suppress LPS-induced productions of INF-$\alpha$ and IL-10 PF and ONO-5046 in each or both showed a trend to increase LPS-induced IL-$\beta$ and IL-6 productions from primary rat alveolar macrophages. (4) PF and ONO-5046 in each or both showed a trend to attenuate LPS-induced mRNA expressions of TNF-$\alpha$ and MCP-1 from primary rat alveolar macrophages but at the same time showed a trend increase iNOS mRNA expression. Conclusion : These results suggest that PF and ONO-5046 may play a role in attenuating inflammation in LPS-induced ALI and that further study is needed to use these drugs as a new supportive therapeutic strategy for ALI.

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