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    Development of Incremental Forging Process for Manufacturing Large Aluminum Cylinder and Flange

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    4์ฐจ ์‚ฐ์—…์˜ ๋ฐœ๋‹ฌ๊ณผ ์นœํ™˜๊ฒฝ ์—๋„ˆ์ง€์— ๋Œ€ํ•œ ๊ด€์‹ฌ์ด ๋†’์•„์ง€๊ณ  ์žˆ๋‹ค. ์ „๊ธฐ ์ž๋™์ฐจ์˜ ๊ฒฝ์šฐ ๋‚ด๋ถ€์˜ ๋ฐฐํ„ฐ๋ฆฌ ๋ฌด๊ฒŒ๋กœ ์ธํ•˜์—ฌ ์ฐจ์ฒด์˜ ๊ฒฝ๋Ÿ‰ํ™” ๊ธฐ์ˆ ์ด ์š”๊ตฌ๋˜๊ณ  ์žˆ๋‹ค. ์ด๋กœ ์ธํ•˜์—ฌ ์ฐจ๋Ÿ‰์˜ ์—ฐ๋น„ ํ–ฅ์ƒ ๋“ฑ์„ ์œ„ํ•ด ๊ฒฝ๋Ÿ‰ํ™”๋ฅผ ์œ„ํ•œ ๋‹ค์–‘ํ•œ ์—ฐ๊ตฌ๊ฐ€ ์ง„ํ–‰๋˜๊ณ  ์žˆ๋‹ค. ํ•ญ๊ณต ์šฐ์ฃผ ๋ฐ ์žฅ๊ฑฐ๋ฆฌ ๋ฐœ์‚ฌ์ฒด์— ๋Œ€ํ•œ ์—ฐ๊ตฌ ๋˜ํ•œ ํ™œ๋ฐœํžˆ ์ง„ํ–‰๋˜๊ณ  ์žˆ๋‹ค. ๊ฒฝ๋Ÿ‰ํ™”๋ฅผ ์œ„ํ•œ ๋งŽ์€ ์—ฐ๊ตฌ๋Š” ๋Œ€๋ถ€๋ถ„ ์•Œ๋ฃจ๋ฏธ๋Š„๊ณผ ๋งˆ๊ทธ๋„ค์Š˜๊ณผ ๊ฐ™์€ ๋น„์ฒ ๊ธˆ์†์„ ์ด์šฉํ•œ ์ œํ’ˆ์„ ์ƒ์‚ฐํ•˜๋Š” ๊ฒƒ์— ์ค‘์ ์„ ๋‘๊ณ  ์žˆ๋‹ค. ๋‹จ์กฐ ๊ณต์ •์œผ๋กœ ์ƒ์‚ฐํ•œ ๋Œ€ํ˜• ๋‹จ์กฐํ’ˆ์€ ๋งŽ์€ ์ด์ ์„ ๊ฐ€์ง€์ง€๋งŒ, ๋†’์€ ๋‹จ์กฐ ํ•˜์ค‘์ด ์š”๊ตฌ๋˜๋ฉฐ ๋Œ€์šฉ๋Ÿ‰ ๋‹จ์กฐ ํ”„๋ ˆ์Šค๋ฅผ ๋ณด์œ ํ•œ ํ˜„์žฅ์—์„œ๋งŒ ์ œ์ž‘ ๊ฐ€๋Šฅํ•˜๋‹ค๋Š” ๋‹จ์ ์ด ์žˆ๋‹ค. ์ด์— ์ž์œ  ๋‹จ์กฐ ๊ณต์ • ์ค‘ ์‹ค๋ฆฐ๋” ํ˜•์ƒ์„ ์ œ์ž‘ํ•˜๋Š”๋ฐ ์ด์ ์ด ์žˆ๋Š” ๋ฉ˜๋“œ๋  ๋‹จ์กฐ๋ฅผ ์ ์šฉํ•˜์˜€๋‹ค. ์ด๋•Œ ์‹ค๋ฆฐ๋” ์ œํ’ˆ์€ ๊ธฐ์šธ๊ธฐ๋ฅผ ๊ฐ€์ง„ ์›๋ฟ” ์‹ค๋ฆฐ๋” ํ˜•์ƒ์ด๊ธฐ ๋•Œ๋ฌธ์— ์ด๋ฅผ ๊ณ ๋ คํ•˜์—ฌ ๋™์ผ ์ฒด์ ์„ ๊ฐ€์ง„ ์˜ˆ๋น„ ์„ฑํ˜•์ฒด๋ฅผ ์„ค๊ณ„ํ•˜์˜€๋‹ค. ์‹œ๋ฎฌ๋ ˆ์ด์…˜๊ณผ ๋‚ฉ ์‹คํ—˜์„ ํ†ตํ•˜์—ฌ ๊ณต์ • ์ดˆ๊ธฐ์— ํฐ ์ง๊ฒฝ ๋ถ€๋ถ„์ด ์ฒ˜์Œ ๋‹จ์กฐ ๋˜์–ด ๊ธธ์ด๋ฐฉํ–ฅ ๋ณ€ํ˜•์œผ๋กœ ์ธํ•˜์—ฌ ์ง๊ฒฝ์„ ๊ฐ์†Œ์‹œํ‚ค๋Š” ๊ฒƒ์œผ๋กœ ํ™•์ธํ•˜์˜€์Šต๋‹ˆ๋‹ค. ์ด์— ์˜ˆ๋น„ ์„ฑํ˜•์ฒด์˜ ์ฒด์ ์„ ๋ณด์ƒํ•˜์—ฌ ์„ค๊ณ„๋ฅผ ์ˆ˜์ •ํ•˜์˜€๋‹ค. ์ˆ˜์ •ํ•œ ์˜ˆ๋น„ ์„ฑํ˜•์ฒด๋Š” ์ง๊ฒฝ ๊ฐ์†Œ ๋ฌธ์ œ๋ฅผ ํšจ๊ณผ์ ์œผ๋กœ ํ•ด๊ฒฐํ•˜์˜€๋‹ค. ์ด๋ฅผ ์‹œ์ œํ’ˆ ์ œ์ž‘์„ ํ†ตํ•˜์—ฌ ๊ฒ€์ฆํ•˜์˜€๋‹ค. ํ”Œ๋žœ์ง€ ์ œํ’ˆ์˜ ๊ฒฝ์šฐ ํšŒ์ „ ๊ธˆํ˜•์„ ์‚ฌ์šฉํ•˜๋Š” ์ ์ง„์  ๋‹จ์กฐ ๊ณต์ •์„ ๊ฐœ๋ฐœํ•˜์˜€๋‹ค. ์ƒˆ๋กœ ๋„์•ˆํ•œ ํšŒ์ „ ๊ธˆํ˜•์€ ๋‹จ์กฐ ํ•˜์ค‘์„ ๊ฐ์†Œํ•˜๊ณ  ์—ด๊ฐ„ ๋‹จ์กฐ๊ณต์ •์—์„œ ๊ณต์ž‘๋ฌผ๊ณผ ๊ธˆํ˜•์˜ ๋ถ€์ฐฉ์„ ๋ฐฉ์ง€ํ•  ์ˆ˜ ์žˆ๋„๋ก ํ•˜์˜€๋‹ค. ์ ์ง„์  ๋‹จ์กฐ ๊ณต์ •์˜ ๊ฐœ๋ฐœ์„ ํ†ตํ•˜์—ฌ ์š”๊ตฌ๋˜๋Š” ๋‹จ์กฐ ํ•˜์ค‘์„ ๊ฐ์†Œํ•จ์œผ๋กœ์จ ๋Œ€์šฉ๋Ÿ‰ ๋‹จ์กฐ ํ”„๋ ˆ์Šค๊ฐ€ ์—†์–ด๋„ ๋ณด๋‹ค ๋งŽ์€ ๊ณต์žฅ์—์„œ ๋ณธ ๊ณต์ •์„ ์ˆ˜์šฉํ•  ์ˆ˜ ์žˆ์„ ๊ฒƒ์œผ๋กœ ์˜ˆ์ƒ๋œ๋‹ค. ๋˜ํ•œ, ์†Œ์žฌ ํšŒ์ˆ˜์œจ์„ ์ ˆ์‚ญ ๊ณต์ •์— ๋น„ํ•˜์—ฌ ํ–ฅ์ƒ์‹œํ‚ฌ ์ˆ˜ ์žˆ๋‹ค. |With the fourth industrial revolution, interest in environmentally friendly energy is increasing. In the case of an electric car, there is a demand for a weight reduction technique for reducing the weight of the whole parts, and various researches are being carried out to reduce weight in various product groups such as raising the fuel efficiency. In addition, researches for lighter weight are being actively carried out in aerospace and medium-range launch vehicles. Most of the researches for lightweighting have been focused on manufacturing products using non-ferrous metals such as aluminum and magnesium. Forged products by die forging have many advantage, but they have a disadvantage that high forging loads are required and can only be made in the factory with large capacity forging presses. For this reason, we applied the mandrel forging, which is advantageous for manufacturing the cylinder shape. In this case, since the cylinder product has a conical cylinder shape having a slope, the preform having the same volume is designed in consideration of this. Through simulations and lead experiments, it was confirmed that the diameter was reduced due to longitudinal deformation by forging the large diameter part at the beginning of the process. The preform design was modified by compensating the volume. The modified preform effectively solved the diameter reduction problem. This was verified through prototype production. In case of a flange product, an incremental forging process with the rotating die was developed. The novel rotating die was suggested th reduce the forging load and to prevent the sticking with workpiece and die in hot forging. Therefore, it is expected that the design process can be available in factories without large-capacity forging presses. Further, the material recovery rate can be improved as compared with the machining process.1. ์„œ ๋ก  1 1.1 ์—ฐ๊ตฌ ๋ฐฐ๊ฒฝ 1 1.2 ์—ฐ๊ตฌ ๋ชฉ์  ๋ฐ ๋‚ด์šฉ 3 2. ๊ฐ•์†Œ์„ฑ ์œ ํ•œ ์š”์†Œ ํ•ด์„์˜ ์ด๋ก ์  ๋ฐฐ๊ฒฝ 6 3. ์‹ค๋ฆฐ๋” ์ œํ’ˆ์˜ ์ œ์ž‘ ๊ณต์ • 10 3.1 ์ ์ง„ ๋‹จ์กฐ ๊ณต์ • ์„ค๊ณ„ 10 3.1.1 ๊ณต์ • ์„ค๊ณ„ 10 3.1.2 ์˜ˆ๋น„ ์„ฑํ˜•์ฒด ์„ค๊ณ„ 12 3.2 ์ ์ง„ ๋‹จ์กฐ ๊ณต์ • ํ•ด์„ 14 3.2.1 ์˜ˆ๋น„ ์„ฑํ˜•์ฒด ๋ฌผ์„ฑ์น˜ 14 3.2.2 ๊ณต์ • ์กฐ๊ฑด 17 3.2.3 ์œ ํ•œ ์š”์†Œ ํ•ด์„ ๊ฒฐ๊ณผ 19 3.2.4 ๋Œ€๋‹จ๋ถ€ ์ฒด์ ์„ ์ฆ๊ฐ€ํ•œ ํ•ด์„ ๊ฒฐ๊ณผ 23 3.3 ๋‚ฉ ์‹คํ—˜์„ ํ†ตํ•œ ์„ฑํ˜• ๊ฐ€๋Šฅ์„ฑ ๊ฒ€์ฆ 26 3.4 ์‹œ์ œํ’ˆ ์ œ์ž‘ 31 3.4.1 ์‹œ์ œํ’ˆ ์ œ์ž‘ ์„ค๋น„ 31 3.4.2 ์‹œ์ œํ’ˆ ์ œ์ž‘ 32 4. ํ”Œ๋žœ์ง€ ์ œํ’ˆ์˜ ์ œ์ž‘ ๊ณต์ • 36 4.1 ํšŒ์ „-๋‹ค๋‹จ ๋‹จ์กฐ ๊ณต์ • ์„ค๊ณ„ 37 4.1.1 ๊ณต์ • ์„ค๊ณ„ 37 4.1.2 ์˜ˆ๋น„ ์„ฑํ˜•์ฒด ์„ค๊ณ„ 39 4.2 ํšŒ์ „-๋‹ค๋‹จ ๋‹จ์กฐ ๊ณต์ • ํ•ด์„ 40 4.2.1 ๊ณต์ • ์กฐ๊ฑด ๋ฐ ์†Œ์žฌ ๋ฌผ์„ฑ์น˜ 40 4.2.2 ํ•ด์„ ๊ฒฐ๊ณผ 43 4.2.3 ์ฝ˜ ๊ธˆํ˜•์„ ๋„์ž…ํ•œ ๊ณต์ • 46 4.3 ์‹œ์ œํ’ˆ ์ œ์ž‘ 50 5. ๊ฒฐ๋ก  54 ์ฐธ๊ณ ๋ฌธํ—Œ 56Maste

    STAT1/2๋ฅผ ๋งค๊ฐœ๋กœ ํ•œ ํฌ๋กœ๋งˆํ‹ด ์‚ผ์ฐจ๊ตฌ์กฐ๊ฐ€ ๊ฐ„์•”์˜ ์„ธํฌ๋…์„ฑ ํ•ญ์•”์ œ ๊ฐ์ˆ˜์„ฑ์— ๋ฏธ์น˜๋Š” ์—ญํ•  ๊ทœ๋ช…

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์œตํ•ฉ๊ณผํ•™๊ธฐ์ˆ ๋Œ€ํ•™์› ๋ถ„์ž์˜ํ•™ ๋ฐ ๋ฐ”์ด์˜ค์ œ์•ฝํ•™๊ณผ, 2019. 2. ๊น€ํƒœ์œ .Type I interferon signaling pathway๋Š” ์„ธํฌ๋…์„ฑํ•ญ์•”์ œ์— ์˜ํ•ด ํ™œ์„ฑํ™”๋˜๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ์œผ๋ฉฐ, ์ด์˜ ํšจ๊ณผ๋กœ anti-tumor immune response ํ˜„์ƒ์„ ์•ผ๊ธฐํ•œ๋‹ค. Type I interferon signaling pathway๋Š” ๋ฐ”์ด๋Ÿฌ์Šค์™€ ๊ฐ™์€ ๋ณ‘์›์ฒด ๊ฐ์—ผ์— ์˜ํ•ด ํ™œ์„ฑํ™” ๋˜๋Š” ์‹ ํ˜ธ์ „๋‹ฌ์ฒด๊ณ„์ด๋‹ค. ๋ฐ”์ด๋Ÿฌ์Šค์˜ ๊ฐ์—ผ์ด ์กด์žฌํ•˜์ง€ ์•Š์œผ๋‚˜ ๋งˆ์น˜ ๊ฐ์—ผ์ด ์žˆ๋Š” ๊ฒƒ์ฒ˜๋Ÿผ ๋ฐ˜์‘ํ•˜์—ฌ ์ด๋Ÿฌํ•œ ์‹ ํ˜ธ์ฒด๊ณ„๋ฅผ ํ™œ์„ฑํ™”์‹œํ‚ค๋Š” ํ˜„์ƒ์„ viral mimicry๋ผ ์ผ์ปซ๋Š”๋‹ค. ๋ณธ ๋…ผ๋ฌธ์—์„œ๋Š” ์„ธํฌ๋…์„ฑํ•ญ์•”์ œ ์ฒ˜๋ฆฌ๋กœ ์ธํ•˜์—ฌ ๊ฐ„์•”์„ธํฌ ๋‚ด์— ๋‚ด์žฌ๋˜์–ด ์žˆ๋˜ Endogenous retrovirus์˜ ๋ฐœํ˜„์ด ํ™œ์„ฑํ™” ๋˜์–ด ๊ทธ์˜ ์ „์‚ฌ์ฒด์ธ dsRNA๊ฐ€ ์ƒ์„ฑ๋˜๋Š” viral mimicry ํ˜„์ƒ์„ ํ™•์ธํ•˜์˜€๋‹ค. ์ด ๋•Œ, dsRNA๊ฐ€ ์ฃผ์š” ๋งค๊ฐœ์ฒด๊ฐ€ ๋˜์–ด ๋‹ค์–‘ํ•œ Interferon stimulated genes (ISGs)์˜ ๋ฐœํ˜„์„ ๋™์‹œ๋‹ค๋ฐœ์ ์œผ๋กœ ์ฆ๊ฐ€์‹œํ‚ค๊ฒŒ ๋˜๋Š”๋ฐ, ์ด ๊ณผ์ •์—์„œ signal transducer and activator of transcription 1/2๋ผ๊ณ  ์•Œ๋ ค์ง„ STAT1๊ณผ STAT2์— ์˜ํ•œ ํฌ๋กœ๋งˆํ‹ด ์‚ผ์ฐจ๊ตฌ์กฐ ํ˜•์„ฑ์ด ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•œ๋‹ค๋Š” ๊ฒƒ์„ ๋ฐํ˜”๋‹ค. ํฌ๋กœ๋งˆํ‹ด ์‚ผ์ฐจ๊ตฌ์กฐ์˜ ํ˜•์„ฑ์€ ์œ ์ „์ž์˜ ๋ฐœํ˜„์„ ์กฐ์ ˆํ•˜๋Š” ๊ฒƒ์œผ๋กœ ์•Œ๋ ค์ ธ ์žˆ๋Š”๋ฐ, ์—ผ์ƒ‰์ฒด ์ƒ์—์„œ ๋ฉ€๋ฆฌ ๋–จ์–ด์ ธ ์žˆ๋Š” ์œ ์ „์ž๋“ค๋กœ ํ•˜์—ฌ๊ธˆ ๋ฌผ๋ฆฌ์ ์œผ๋กœ ๊ฐ€๊น๊ฒŒ ํ•˜์—ฌ ํšจ๊ณผ์ ์ธ ์œ ์ „์ž๋ฐœํ˜„์„ ์กฐ์ ˆํ•˜๊ฒŒ ๋œ๋‹ค. ์„ธํฌ๋…์„ฑํ•ญ์•”์ œ ํ˜น์€ dsRNA ํ•ฉ์„ฑ๋ฌผ์งˆ์„ ์ฒ˜๋ฆฌํ•˜๊ฒŒ ๋˜๋ฉด, ISG locus์—์„œ์˜ STAT1๊ณผ 2์˜ ๊ฒฐํ•ฉ์ด ์ฆ๊ฐ€ํ•จ๊ณผ ๋™์‹œ์— ์‚ผ์ฐจ๊ตฌ์กฐ๊ฐ€ ํ˜•์„ฑ๋˜๋Š” ๊ฒƒ์„ ํ™•์ธํ•˜์˜€๋‹ค. ์ด๋Ÿฌํ•œ ํ˜„์ƒ์€ STAT1/2๋ฅผ CRISPR/Cas9 KO system์„ ์ด์šฉํ•˜์—ฌ ๋ฐœํ˜„์„ ๊ฐ์†Œ์‹œ์ผฐ์„ ๋•Œ ์‚ฌ๋ผ์ง€๋Š” ๊ฒƒ์„ ์ฆ๋ช…ํ•˜์˜€๋‹ค. ๋˜ํ•œ, IFIT1์—์„œ STAT1/2์˜ ๊ฒฐํ•ฉํ•˜๋Š” ๋ถ€์œ„๋ฅผ CRISPR system์„ ์ด์šฉํ•˜์—ฌ ์ž˜๋ผ๋ƒˆ์„ ๋•Œ์—๋„ ๋™์ผํ•œ ํ˜„์ƒ์ด ๋‚˜ํƒ€๋‚จ์„ ์ฆ๋ช…ํ•˜์˜€๋‹ค. ์„ธํฌ๋…์„ฑํ•ญ์•”์ œ์— ๋Œ€ํ•œ ๊ฐ์ˆ˜์„ฑ์€ STAT1์˜ ๋ฐœํ˜„์ด ์ €ํ•ด๋˜์—ˆ์„ ๋•Œ ๊ฐ์†Œํ•˜๋Š” ์–‘์ƒ์„ ๋ณด์˜€๋‹ค. ์ด๋ฅผ ๋ฐ”ํƒ•์œผ๋กœ STAT1/2๋ฅผ ๋งค๊ฐœ๋กœ ํ•œ ํฌ๋กœ๋งˆํ‹ด ์‚ผ์ฐจ๊ตฌ์กฐ๊ฐ€ ISG์˜ ๋ฐœํ˜„์„ ๊ฒฐ์ •ํ•˜๋Š” ๋ฐ์— ์ค‘์š”ํ•œ ์—ญํ• ์„ ํ•˜๋ฉฐ, ์ด๋Š” ์„ธํฌ๋…์„ฑํ•ญ์•”์ œ์— ๋Œ€ํ•œ ํšจ๊ณผ์— ์˜ํ–ฅ์„ ๋ฏธ์น˜๋Š” ๊ฒƒ์„ ๋ณธ ๋…ผ๋ฌธ์„ ํ†ตํ•ด ๊ทœ๋ช…ํ•˜์˜€๋‹ค.Anti-tumor effects of chemotherapeutic agents are known to induce type ฮ™ interferon signaling pathways that enhance the immunogenicity of dying cancer cells, and thereby stimulate anti-tumor immune response. The chemotherapeutic agent induced immune response is termed as viral mimicry, as these type ฮ™ interferon related gene signatures are similar to those induced by viral pathogens. Here we demonstrate that treatment of chemotherapeutic agents stimulates rapid production of multiple interferon-stimulated genes (ISGs) via double-stranded RNAs derived from endogenous retroviruses in human hepatocellular carcinoma cells. Clustered ISG locus forms higher-order chromatin structure mediated by signal transducer and activator of transcription 1/2 (STAT1/2) during coordinate transcriptional regulation of these genes after chemotherapy. The finely tuned regulation of multiple ISGs transcription is abrogated when physical proximity is destroyed by STAT1 depletion. In addition, chemotherapeutic efficacy is abrogated when STAT1 expression is destroyed. Overall, our results suggest that transcriptional regulation of ISGs by STAT1/2-mediated higher-order chromatin structure is crucial for the efficient anti-tumor treatmentTable of Contents Abstract -------------------------------------------------------------------------โ…ฐ Table of Contents -------------------------------------------------------------โ…ฒ List of Tables ------------------------------------------------------------------โ…ณ List of Figures -----------------------------------------------------------------โ…ด 1. Introduction --------------------------------------------------------------1 2. Materials and Methods ------------------------------------------------4 3. Results -------------------------------------------------------------------14 4. Discussion ---------------------------------------------------------------40 5. References --------------------------------------------------------------44 Abstract in Korean --------------------------------------------------------------48Maste

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