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    ๊ณ„์ ˆ๋‚ด ๋ฐ ๊ณ„์ ˆ (S2S) ์˜ˆ์ธก์„ ์œ„ํ•œ ์ ์ ˆํ•œ ์•™์ƒ๋ธ” ํฌ๊ธฐ ์„ค์ •์— ๋Œ€ํ•œ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์ž์—ฐ๊ณผํ•™๋Œ€ํ•™ ์ง€๊ตฌํ™˜๊ฒฝ๊ณผํ•™๋ถ€,2019. 8. ์†์„์šฐ.In this study, the optimal ensemble size and the factor affecting its determination for Sub-seasonal to Seasonal (S2S) prediction are explored. The results show that the prediction skill, which is quantified by the mean square skill score (MSSS), increases with increasing ensemble size in a perfect model with an unbiased and reliable ensemble spread to observed variance. In this idealized prediction system, 10 to 20 ensemble members lead to 90% to 95% of the skill improvement in the theoretical maximum (infinite ensemble size). This theoretical estimation is applied to the European Centre for Medium-Range Weather Forecasts (ECMWF) S2S real-time forecast that consists of 51 ensemble members. The MSSS of the 500-hPa geopotential height, which represents tropospheric skill, is in good agreement with the theoretical estimation, indicating that approximately 10 to 20 members are needed to obtain a skill improvement close to the theoretical maximum. However, the stratospheric skill, verified at the 50-hPa geopotential height, is substantially lower than the theoretical estimation. This result is particularly true in the tropical stratosphere, where only 20-30% skill improvement of the theoretical maximum can be obtained even when using all ensemble members. The substantial overestimation of the stratospheric skill is mainly due to model mean bias. The role of mean bias in the ensemble size effect is highly dependent on ensemble spread and natural variability. By removing the bias, overestimation in the stratosphere can be reduced so that it is possible for 10-20 members to be optimal. Extending the results to all the levels and seasons available in the S2S dataset indicates that the effect of mean bias is remarkable in the tropical and summer hemispheric upper stratosphere.๋ณธ ์—ฐ๊ตฌ๋Š” ๊ณ„์ ˆ๋‚ด ๋ฐ ๊ณ„์ ˆ(S2S) ์˜ˆ์ธก์„ ์œ„ํ•œ ์ตœ์ ์˜ ์•™์ƒ๋ธ” ํฌ๊ธฐ์™€ ๊ทธ ๊ฒฐ์ •์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ์š”์ธ์— ๋Œ€ํ•ด ๋‹ค๋ฃจ๊ณ  ์žˆ๋‹ค. ๋ฐ”์ด์–ด์Šค๊ฐ€ ์—†๊ณ  ๊ด€์ธก์˜ ๋ถ„์‚ฐ์— ์ž˜ ๋ถ€ํ•ฉํ•˜๋Š” ์•™์ƒ๋ธ” ์Šคํ”„๋ ˆ๋“œ๋ฅผ ๊ฐ–์ถ˜ ์™„๋ฒฝํ•œ ๋ชจ๋ธ์—์„œ, ํ‰๊ท ์ œ๊ณฑ๊ธฐ์ˆ (Mean Square Skill Score; MSSS)๋กœ ์ •๋Ÿ‰ํ™”๋˜๋Š” ๋ชจ๋ธ์˜ ์˜ˆ์ธก์„ฑ์€ ์•™์ƒ๋ธ” ํฌ๊ธฐ๊ฐ€ ์ฆ๊ฐ€ํ•จ์— ๋”ฐ๋ผ ํ•ญ์ƒ ํ–ฅ์ƒ๋ฉ๋‹ˆ๋‹ค. ์ด๋Ÿฌํ•œ ์ด์ƒ์ ์ธ ์˜ˆ์ธก์‹œ์Šคํ…œ์—์„œ 10-20๊ฐœ์˜ ์•™์ƒ๋ธ” ๋ฉค๋ฒ„๊ฐ€ ์žˆ์œผ๋ฉด ์ด๋ก ์ ์œผ๋กœ ์–ป์„ ์ˆ˜ ์žˆ๋Š” ์ตœ๋Œ€(๋ฌดํ•œ ๊ฐœ ์•™์ƒ๋ธ” ๋ฉค๋ฒ„)์˜ 90์—์„œ 95%์— ํ•ด๋‹นํ•˜๋Š” ์˜ˆ์ธก์„ฑ ํ–ฅ์ƒ์„ ๊ธฐ๋Œ€ํ•  ์ˆ˜ ์žˆ๋‹ค. 51๊ฐœ์˜ ์•™์ƒ๋ธ” ๋ฉค๋ฒ„๋ฅผ ๊ฐ€์ง„ ์œ ๋Ÿฝ์ค‘๊ธฐ์˜ˆ์ธก์„ผํ„ฐ(European Centre for Medium-Range Weather Forecasts; ECMWF)์˜ S2S ์‹ค์‹œ๊ฐ„ ์˜ˆ์ธก ์ž๋ฃŒ๋ฅผ ์œ„์˜ ์ด๋ก ์  ์ถ”์ •๊ณผ ๋น„๊ตํ•˜์˜€๋‹ค. ๋Œ€๋ฅ˜๊ถŒ์˜ ์˜ˆ์ธก์„ฑ์„ ๋‚˜ํƒ€๋‚ด๋Š” 500-hPa ์ง€์œ„๊ณ ๋„์˜ MSSS๋Š” ์ด๋ก ์ ์ธ ์ถ”์ •์น˜์™€ ์ž˜ ์ผ์น˜ํ•˜๋ฉฐ, ์ด๋Š” 10-20๊ฐœ์˜ ๋ฉค๋ฒ„๋กœ ์ด๋ก ์ ์ธ ์ตœ๋Œ€์น˜์— ๊ทผ์ ‘ํ•œ ์˜ˆ์ธก์„ฑ ํ–ฅ์ƒ์„ ์–ป์„ ์ˆ˜ ์žˆ์Œ์„ ์˜๋ฏธํ•œ๋‹ค. ๊ทธ๋Ÿฌ๋‚˜ 50-hPa ์ง€์œ„๊ณ ๋„์˜ MSSS๋กœ ํ‰๊ฐ€๋œ ์„ฑ์ธต๊ถŒ ์˜ˆ์ธก์„ฑ์€ ์ด๋ก ์  ์ถ”์ •์— ๋น„ํ•ด ์ƒ๋‹นํžˆ ๋‚ฎ์€ ๊ฒƒ์œผ๋กœ ๋‚˜ํƒ€๋‚ฌ๋‹ค. ํŠนํžˆ ์—ด๋Œ€ ์„ฑ์ธต๊ถŒ ์˜์—ญ์—์„œ๋Š” ๋ชจ๋“  ์•™์ƒ๋ธ” ๋ฉค๋ฒ„๋ฅผ ์‚ฌ์šฉํ–ˆ์„ ๋•Œ์—๋„ ์˜ˆ์ธก์„ฑ ํ–ฅ์ƒ์ด ์ด๋ก ๊ฐ’์˜ 20-30% ์ˆ˜์ค€์— ๋ถˆ๊ณผํ–ˆ๋‹ค. ์„ฑ์ธต๊ถŒ์—์„œ ๋‚˜ํƒ€๋‚˜๋Š” ๊ณผ๋Œ€์ถ”์ • ๊ฒฝํ–ฅ์€ ์ฃผ๋กœ ๋ชจ๋ธ์˜ ํ‰๊ท  ๋ฐ”์ด์–ด์Šค์— ๊ธฐ์ธํ•œ๋‹ค. ์ด ๊ฐ™์€ ์•™์ƒ๋ธ” ํฌ๊ธฐ ํšจ๊ณผ์— ๋Œ€ํ•œ ๋ฐ”์ด์–ด์Šค์˜ ์˜ํ–ฅ์€ ์•™์ƒ๋ธ” ์Šคํ”„๋ ˆ๋“œ์™€ ๊ด€์ธก์˜ ๋ถ„์‚ฐ์— ํฌ๊ฒŒ ์˜ํ–ฅ์„ ๋ฐ›๋Š”๋‹ค. ๋‹จ์ˆœํžˆ ๋ฐ”์ด์–ด์Šค๋ฅผ ์ œ๊ฑฐํ•˜๋Š” ๋ฐ”์ด์–ด์Šค ๋ณด์ •(bias correction)์„ ํ†ตํ•ด ์„ฑ์ธต๊ถŒ์—์„œ์˜ ๊ณผ๋Œ€์ถ”์ •์„ ์™„ํ™”ํ•  ์ˆ˜ ์žˆ์œผ๋ฉฐ, ๋Œ€๋ฅ˜๊ถŒ๊ณผ ๋งˆ์ฐฌ๊ฐ€์ง€๋กœ 10-20๊ฐœ๋ฅผ ์ตœ์  ์•™์ƒ๋ธ” ๊ทœ๋ชจ๋กœ ์ทจํ•  ์ˆ˜ ์žˆ๋‹ค. ์ „์ฒด ๊ณ ๋„์™€ ๊ณ„์ ˆ์— ๋Œ€ํ•œ ํ™•์žฅ์„ ํ†ตํ•ด, ์—ด๋Œ€ ๋ฐ ์—ฌ๋ฆ„๋ฐ˜๊ตฌ ์ƒ๋ถ€ ์„ฑ์ธต๊ถŒ์—์„œ ๋™์ผํ•˜๊ฒŒ ๋ฐ”์ด์–ด์Šค์˜ ์˜ํ–ฅ์ด ๊ทน๋ช…ํ•˜๊ฒŒ ๋‚˜ํƒ€๋‚จ์„ ํ™•์ธํ•  ์ˆ˜ ์žˆ๋‹ค.1. Introduction 1 2. Methodology 4 2.1. Error Estimation in a Perfect Model 4 2.2. Evaluation Metrics (MSSS and SIR) 7 3. Application to the S2S Prediction System 10 3.1. ECMWF S2S Real-time Forecast 10 3.2. Prediction skills 11 3.3. Role of Mean Bias in Overestimation of Skill 13 3.4. Vertical and Seasonal Extension 18 4. Summary and Conclusions 21 References 24 Table 28 Figures 29 Abstract in Korean 40Maste

    ์‹ ํ–‰์ •์ˆ˜๋„ ๊ฑด์„ค์˜ ์‚ฌํšŒยท๊ฒฝ์ œ์  ํŒŒ๊ธ‰์˜ํ–ฅ ๋ถ„์„์—ฐ๊ตฌ(The soco-economic impact analysis on the construction of new capital in Korea)

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    ๋…ธํŠธ : ์ด ์—ฐ๊ตฌ๋ณด๊ณ ์„œ์˜ ๋‚ด์šฉ์€ ๊ตญํ† ์—ฐ๊ตฌ์›์˜ ์ž์ฒด ์—ฐ๊ตฌ๋ฌผ๋กœ์„œ ์ •๋ถ€์˜ ์ •์ฑ…์ด๋‚˜ ๊ฒฌํ•ด์™€๋Š” ์ƒ๊ด€์—†์Šต๋‹ˆ๋‹ค

    ์ง€์—ญ๊ฐœ๋ฐœ์‚ฌ์—…์˜ ํšจ์œจ์  ์ถ”์ง„์„ ์œ„ํ•œ SOCํˆฌ์ž ์—ฐ๊ณ„์ง‘ํ–‰ ๋ฐฉ์•ˆ

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    ๋…ธํŠธ : ์ด ์—ฐ๊ตฌ๋ณด๊ณ ์„œ์˜ ๋‚ด์šฉ์€ ๊ตญํ† ์—ฐ๊ตฌ์›์˜ ์ž์ฒด ์—ฐ๊ตฌ๋ฌผ๋กœ์„œ ์ •๋ถ€์˜ ์ •์ฑ…์ด๋‚˜ ๊ฒฌํ•ด์™€๋Š” ์ƒ๊ด€์—†์Šต๋‹ˆ๋‹ค

    ๋น„์šฉ์ข…์„ ๋™๋ฐ˜ํ•œ ํ˜ธ์‚ฐ๊ตฌ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ์— ๋Œ€ํ•œ resveratrol์˜ ์น˜๋ฃŒํšจ๊ณผ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜ํ•™๊ณผ ์ด๋น„์ธํ›„๊ณผํ•™ ์ „๊ณต, 2012. 8. ๋ฏผ์–‘๊ธฐ.์„œ๋ก : ๋งŒ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ์€ ์ฝ”๋ง‰ํž˜๊ณผ ํ›„๊ฐ์žฅ์•  ๋“ฑ์˜ ์ฆ์ƒ์„ ์œ ๋ฐœํ•˜๊ณ  ์‚ถ์˜ ์งˆ์„ ๋–จ์–ด๋œจ๋ฆฌ๋Š” ์งˆํ™˜์ด๋ฉฐ ํ”ํžˆ ๋น„์šฉ์ข…์„ ๋™๋ฐ˜ํ•œ๋‹ค. ์Šคํ…Œ๋กœ์ด๋“œ ์ œ์ œ์˜ ์ „์‹ ์  ํˆฌ์—ฌ๋Š” ๋น„์šฉ์ข…์— ๋Œ€ํ•œ ๋งค์šฐ ํšจ๊ณผ์ ์ธ ์•ฝ๋ฌผ ์น˜๋ฃŒ์ด๋‚˜ ์žฅ๊ธฐ๊ฐ„ ์‚ฌ์šฉํ•˜๊ฒŒ ๋˜๋ฉด ๊ณจ๋‹ค๊ณต์ฆ, ์šฐ์šธ์ฆ ๋ฐ ๋‹น๋‡จ ๋“ฑ์˜ ํ•ฉ๋ณ‘์ฆ์„ ์œ ๋ฐœํ•˜๋ฏ€๋กœ ์ œํ•œ์ ์œผ๋กœ ์‚ฌ์šฉํ•  ์ˆ˜ ๋ฐ–์— ์—†๋‹ค. ์ตœ๊ทผ ํฌ๋„์ƒ๊ตฌ๊ท  ์žฅ๋…์†Œ Bํ˜•์„ ์ด์šฉํ•œ ํ˜ธ์‚ฐ๊ตฌ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ ๋งˆ์šฐ์Šค ๋ชจ๋ธ์ด ํ™•๋ฆฝ๋˜์—ˆ๋Š”๋ฐ ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” resveratrol์ด ๋น„์šฉ์ข…์„ ๋™๋ฐ˜ํ•œ ํ˜ธ์‚ฐ๊ตฌ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ์— ๋ฏธ์น˜๋Š” ์น˜๋ฃŒ ํšจ๊ณผ์™€ ๊ทธ ์ž‘์šฉ ๊ธฐ์ „์— ๋Œ€ํ•ด์„œ ํƒ๊ตฌํ•˜์˜€๋‹ค. ๋Œ€์ƒ ๋ฐ ์—ฐ๊ตฌ ๋ฐฉ๋ฒ•: ์‹คํ—˜๊ตฐ์€ ๋‚œ์•Œ๋ถ€๋ฏผ์œผ๋กœ ๊ฐ์ž‘์‹œํ‚ค๊ณ  ์Œ์„ฑ๋Œ€์กฐ๊ตฐ์—๋Š” PBS๋ฅผ ํˆฌ์—ฌํ•˜์˜€๋‹ค. ์‹คํ—˜๊ตฐ์€ ์‹คํ—˜ ํ›„๋ฐ˜ 8์ฃผ๊ฐ„ ๋งค์ฃผ ํ•œ ๋ฒˆ์”ฉ ํฌ๋„์ƒ๊ตฌ๊ท  ์žฅ๋…์†Œ Bํ˜•์œผ๋กœ ๋น„๊ฐ•๋‚ด ์ž๊ทน์„ ์‹œํ–‰ํ•˜์˜€์œผ๋ฉฐ ์ฃผ์ž…ํ•œ ์•ฝ๋ฌผ์— ๋”ฐ๋ผ 4๊ทธ๋ฃน์œผ๋กœ ๋‚˜๋ˆ„์—ˆ๋‹ค. ์–‘์„ฑ๋Œ€์กฐ๊ตฐ์—๋Š” DMSO์™€ PBS์˜ ํ˜ผํ•ฉ๋ฌผ์„ ์ฃผ์ž…ํ•˜์˜€๊ณ  ๋‚˜๋จธ์ง€ ์„ธ ์น˜๋ฃŒ๊ตฐ์—๋Š” ๊ฐ๊ฐ triamcinolone acetonide, ์ €๋†๋„ resveratrol, ๊ณ ๋†๋„ resveratrol์„ ํˆฌ์—ฌํ•˜์˜€๋‹ค. ์ „๋ฐ˜์ ์ธ ์—ผ์ฆ ์ƒํƒœ์™€ ๋น„์šฉ์ข… ๊ด€์ฐฐ์„ ์œ„ํ•œ Hemoxylin eosin ์—ผ์ƒ‰, ํ˜ธ์‚ฐ๊ตฌ ์นจ์œค ๊ด€์ฐฐ์„ ์œ„ํ•œ Sirius red ์—ผ์ƒ‰, ๋น„๋ฐ˜์„ธํฌ ๊ด€์ฐฐ์„ ์œ„ํ•œ Giemsa ์—ผ์ƒ‰, ์ƒํ”ผํ•˜ ์„ฌ์œ ํ™” ํ™•์ธ์„ ์œ„ํ•œ Massons trichrome ์—ผ์ƒ‰, ๋ถ„๋น„์„ธํฌ์˜ ํ˜•์„ฑ์„ ๊ด€์ฐฐํ•˜๊ธฐ ์œ„ํ•ด Alcian blue ์—ผ์ƒ‰์„ ์‹œํ–‰ํ•˜์˜€๋‹ค. ๋˜ํ•œ, ๋ฉด์—ญ์กฐ์งํ™”ํ•™์—ผ์ƒ‰๊ณผ Western blot์„ ์‹œํ–‰ํ•˜์—ฌ ๊ทธ๋ฃน๊ฐ„ cyclooxygense-2์™€ 5-lipooxygense์˜ ๋ฐœํ˜„ ์ •๋„๋ฅผ ๋น„๊ตํ•˜์˜€์œผ๋ฉฐ, ์‹ค์‹œ๊ฐ„ PCR์„ ์‹œํ–‰ํ•˜์—ฌ IL-4, IL-5, prostaglandin D synthase ๋ฐ leukotriene C4 synthase ์œ ์ „์ž์˜ ๋ฐœํ˜„ ์ •๋„๋ฅผ ๊ทธ๋ฃน๊ฐ„์— ๋น„๊ตํ•˜์˜€๋‹ค. ๊ฒฐ๊ณผ: ๊ณ ๋†๋„ resveratrol์„ ํˆฌ์—ฌํ•œ ์‹คํ—˜๊ตฐ์—์„œ ์กฐ์ง๋‚ด ํ˜ธ์‚ฐ๊ตฌ ์นจ์œค, ์ƒํ”ผํ•˜ ์„ฌ์œ ํ™” ๋ฐ ์ „์ฒด ์—ผ์ฆ ์„ธํฌ ์ค‘ ํ˜ธ์‚ฐ๊ตฌ์˜ ๋น„์œจ ๋“ฑ์ด ์–‘์„ฑ ๋Œ€์กฐ๊ตฐ์— ๋น„ํ•ด ์˜๋ฏธ์žˆ๊ฒŒ ๊ฐ์†Œํ•˜์˜€์œผ๋ฉฐ triamcinolone acetonide์™€ ๋น„์Šทํ•œ ํšจ๊ณผ๋ฅผ ๋ณด์—ฌ์ฃผ์—ˆ๋‹ค. ๋˜ํ•œ, ํ†ต๊ณ„์ ์ธ ์œ ์˜์„ฑ์„ ์–ป์„ ์ˆ˜๋Š” ์—†์—ˆ์ง€๋งŒ ๋น„์šฉ์ข…์˜ ๊ฐฏ์ˆ˜๋„ ๊ฐ์†Œํ•˜๋Š” ๊ฒฝํ–ฅ์„ ๋ณด์˜€๋‹ค. ํ•œํŽธ, ๋ฉด์—ญ์กฐ์งํ™”ํ•™์—ผ์ƒ‰๊ณผ Western blot์—์„œ๋„ ๊ณ ๋†๋„ resveratrol์ด triamcinolone acetonide์™€ ๋น„์Šทํ•œ 5-lipooxygense ๋ฐœํ˜„ ์–ต์ œ ํšจ๊ณผ๋ฅผ ๋ณด์˜€๋‹ค. ๋˜ํ•œ, IL-4, IL-5, prostaglandin D synthase ๋ฐ leukotriene C4 synthase์˜ ์œ ์ „์ž ๋ฐœํ˜„์€ ์–‘์„ฑ ๋Œ€์กฐ๊ตฐ์—์„œ ๊ฐ€์žฅ ๋†’๊ฒŒ ๋‚˜ํƒ€๋‚ฌ์œผ๋ฉฐ, ์ €๋†๋„ ๋ฐ ๊ณ ๋†๋„ resveratrol์„ ํˆฌ์—ฌํ•œ ๊ตฐ ๋ชจ๋‘์—์„œ ์œ ์˜ํ•˜๊ฒŒ ๊ฐ์†Œํ•˜์˜€๋‹ค. ์ €๋†๋„ resveratrol์€ ์ „์ฒด์ ์ธ ํ˜ธ์‚ฐ๊ตฌ ์—ผ์ฆ์„ ๋šœ๋ ทํ•˜๊ฒŒ ์ค„์ด์ง€๋Š” ๋ชปํ–ˆ์ง€๋งŒ ์ „์ฒด ์—ผ์ฆ ์„ธํฌ ์ค‘ ํ˜ธ์‚ฐ๊ตฌ์˜ ๋น„์œจ๊ณผ ์ƒํ”ผํ•˜ ์„ฌ์œ ํ™” ์ •๋„๋ฅผ ๊ฐ์†Œ์‹œํ‚ค๋Š” ํšจ๊ณผ๋ฅผ ๋ณด์˜€๋‹ค. ๊ฒฐ๋ก : ํ˜ธ์‚ฐ๊ตฌ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ ๋งˆ์šฐ์Šค ๋ชจ๋ธ์—์„œ resveratrol์„ ๊ณ ๋†๋„๋กœ ํˆฌ์—ฌํ•˜๋Š” ๊ฒฝ์šฐ ๋šœ๋ ทํ•œ ํ•ญ์—ผ์ฆ ์ž‘์šฉ๊ณผ ๋น„์šฉ์ข… ๊ฐ์†Œ ํšจ๊ณผ๋ฅผ ํ™•์ธํ•  ์ˆ˜ ์žˆ์—ˆ์œผ๋ฉฐ, lipooxygense pathway ์˜ ๋ฐœํ˜„ ์–ต์ œ๊ฐ€ ์ค‘์š”ํ•œ ๊ธฐ์ „์œผ๋กœ ์ƒ๊ฐ๋œ๋‹ค. Resveratrol์€ ๋น„์šฉ์ข…์„ ๋™๋ฐ˜ํ•œ ํ˜ธ์‚ฐ๊ตฌ์„ฑ ๋น„๋ถ€๋น„๋™์—ผ์˜ ์ƒˆ๋กœ์šด ํ›„๋ณด ์น˜๋ฃŒ์ œ๋กœ ํ–ฅํ›„ ํ™˜์ž์— ๋Œ€ํ•œ ์ž„์ƒ ์—ฐ๊ตฌ๊ฐ€ ํ•„์š”ํ•  ๊ฒƒ์œผ๋กœ ๋ณด์ธ๋‹ค.Background: Patients with chronic rhinosinusitis often suffer from nasal stuffiness, olfactory dysfunction, and the decline of quality of life. Chronic rhinosinusitis is frequently accompanied by nasal polyps. Although systemic administration of corticosteroids is efficient medical treatment for nasal polyps, it cannot be used for long-term periods because of its detrimental side effects such as osteoporosis, depression and diabetes mellitus. Therefore, search for safe and effective novel drugs for nasal polyps is needed. Recently, a murine model of eosinophilic rhinosinusitis with nasal polyps was established by using Staphylococcus aureus enterotoxin B. Using the same protocols, therapeutic effects of resveratrol on eosinophilic rhinosinusitis with nasal polyps were examined, and the mechanism of actions were investigated in this study. Materials and Methods: Mice in the experimental groups were sensitized with ovalbumin whereas those in the control group received phosphate-buffered saline. Experimental groups were challenged intranasally with Staphylococcus aureus enterotoxin B weekly during the late 8 weeks of experiments, and divided into 4 subgroups according to the administered drugs: a mixture of dimethyl sulfoxide and phosphate-buffered saline, triamcinolone acetonide, low-dose and high-dose resveratrol. Histopathologic changes were observed using hemotoxylin and eosin for overall inflammation and polyp-like lesions, Sirius red for eosinophils, Giemsa for mast cells, Massons trichrome for collagen, and alcian blue staining for secretory cells. The expression of cyclooxygense-2 and 5-lipooxygense were evaluated by immunohistochemical staining and Western blot analysis. The levels of interleukin (IL)-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase transcripts were determined by quantitative real-time PCR. The differences in histologic and immunologic findings were compared between groups. Results: The degree of eosinophilic infiltration and subepithelial fibrosis, the proportion of eosinophils in total inflammatory cells were significantly decreased by administration of high-dose resveratrol, and its potency was similar to that of triamcinolone acetonide. By means of immunohistochemical staining and Western blot analysis, it was identified that 5-lipooxygenase expression was strongly inhibited by high-dose resveratrol. The gene expression of IL-4, IL-5, prostaglandin D synthase, and leukotriene C4 synthase was highest in mice with eosinophilic rhinosinusitis with nasal polyps, and administration of low- or high-dose resveratrol lowered their expression significantly. The number of polyp-like lesions also decreased, but this change was not statistically significant. Although low-dose resveratrol did not show definite anti-inflammatory effects, it reduced the proportion of eosinophils in total inflammatory cells and the degree of subepithelial fibrosis. Conclusion: Resveratrol, particularly in a high dose, exhibited apparent anti-inflammatory and polyp-reducing effects in a murine model of eosinophilic rhinosinusitis with nasal polyps, and a key mechanism of its action is believed to be the inhibition of the lipooxygenase pathway. Resveratrol appears to be a new potential drug for the treatment of eosinophilic rhinosinusitis with nasal polyps although a further human study is needed to confirm it.Abstract ------------------------------------------------------------------------------------ i Contents ---------------------------------------------------------------------------------- iv List of Figures --------------------------------------------------------------------------- v List of Abbreviations ------------------------------------------------------------------ vii Introduction --------------------------------------------------------------------------------1 Materials and Methods -----------------------------------------------------------------3 Results ------------------------------------------------------------------------------------10 Discussion -------------------------------------------------------------------------------16 References ------------------------------------------------------------------------------25 Figures -----------------------------------------------------------------------------------34 Abstract (Korean) ----------------------------------------------------------------------48 Acknowledgement ---- ----------------------------------------------------------------50Docto

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