77 research outputs found

    ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€ ์ œ์•ˆ ๋ฐ ๋…ธ์ถœํ‰๊ฐ€ : propylene glycol monomethyl ether acetate, ethyl lactate

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    ์‚ฐ์—…๋ณด๊ฑด์ „๊ณต/์„์‚ฌ์—ฐ๊ตฌ๋ชฉ์ : ๋ณธ ์—ฐ๊ตฌ๋Š” ๋ฐ˜๋„์ฒด ์ œ์กฐ๊ณต์ •์—์„œ ํฌํ† ๋ ˆ์ง€์ŠคํŠธ ์œ ๊ธฐ์šฉ๋งค๋กœ ๊ด‘๋ฒ”์œ„ํ•˜๊ฒŒ ์‚ฌ์šฉ๋˜๋‚˜ ๊ตญ๋‚ด ์ž‘์—…ํ™˜๊ฒฝ ๋…ธ์ถœ๊ธฐ์ค€์ด ์—†๋Š” PGMEA, ์ –์‚ฐ ์—ํ‹ธ(Ethyl lactate)์— ๋Œ€ํ•ด ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€์„ ์„ค์ •ํ•˜๊ณ , ์ทจ๊ธ‰ ์‚ฌ์—…์žฅ์˜ ์‹คํƒœ ์กฐ์‚ฌ๋ฅผ ํ†ตํ•ด ์ œ์•ˆ๋œ ๊ธฐ์ค€๊ณผ ์ž‘์—…ํ™˜๊ฒฝ ๊ด€๋ฆฌ ์ˆ˜์ค€์„ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค.์—ฐ๊ตฌ๋Œ€์ƒ ๋ฐ ๋ฐฉ๋ฒ•: ๊ด€๋ฆฌ๊ธฐ์ค€ ์„ค์ • ๋ฐฉ๋ฒ•์œผ๋กœ REACH TGD ๋ฐ ECETOC TRA์— ์˜ํ•œ EU DNELs, EPA RfC, ์‚ฐ์—…์•ˆ์ „๋ณด๊ฑด๊ณต๋‹จ์—์„œ ์ œ์‹œํ•œ RfCwork ๋“ฑ์„ ์‚ฌ์šฉํ•˜์˜€๋‹ค. PGMEA, ์ –์‚ฐ ์—ํ‹ธ๊ณผ ์œ ์‚ฌํ•œ ํŠน์„ฑ์„ ๊ฐ€์ง€๋ฉฐ, ๋…ธ์ถœ๊ธฐ์ค€์ด ์žˆ๋Š” 2-ethoxyethyl acetate, n-butyl lactate๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•œ ํ‰๊ฐ€๊ธฐ๋ฒ• ๊ฒ€์ •์„ ํ†ตํ•ด ๋„์ถœ๋œ ๋ฐฉ๋ฒ•์„ ์ ์šฉํ•˜์—ฌ ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€์„ ์ œ์•ˆํ•˜๊ณ , ํ•œ ๋ฐ˜๋„์ฒด ์‚ฌ์—…์žฅ์—์„œ ๋…ธ์ถœํ‰๊ฐ€๋ฅผ ์ˆ˜ํ–‰ํ•˜์˜€๋‹ค.์—ฐ๊ตฌ๊ฒฐ๊ณผ: ECETOC TRA์— ์˜ํ•œ ํก์ž… DNELs์€ ๊ทœ์ œ์ˆ˜์ค€์˜ 20%๋ฅผ ์ดˆ๊ณผํ•œ ๊ฐ’์„ ๋‚˜ํƒ€๋‚ด์—ˆ๊ณ , EPA RfC ๋ฐฉ๋ฒ•์€ ๊ทผ๋กœ์ž ๋…ธ์ถœ์กฐ๊ฑด์— ์ ํ•ฉํ•˜์ง€ ์•Š์•„ ์ œ์™ธํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ PGMEA, Ethyl lactate์— ๋Œ€ํ•œ ๊ด€๋ฆฌ๊ธฐ์ค€์œผ๋กœ REACH TGD์— ์˜ํ•œ ์ž‘์—…์ž ํก์ž… DNELs์™€ ๊ตญ๋‚ด RfCwork์˜ ๋ฒ”์œ„๊ฐ’์ธ 6.75mg/ใŽฅ(1.25ppm) ~ 21.7mg/ใŽฅ(4ppm) ๋ฐ 0.38mg/ใŽฅ(0.17ppm) ~ 5.36mg/ใŽฅ(1.1ppm)์œผ๋กœ ์„ค์ •ํ•˜์˜€๋‹ค. ์ด์— ์ž‘์—…ํ™˜๊ฒฝ์ธก์ • ๊ฒ€์ถœํ•œ๊ณ„๊ฐ’์„ ๊ณ ๋ คํ•˜์—ฌ ๊ด€๋ฆฌ๊ธฐ์ค€์€ 4ppm, 1.1ppm ์ดํ•˜๋กœ ์ œ์•ˆํ•˜์˜€๋‹ค. ๊ทธ๋ฆฌ๊ณ  ํ•œ ๋ฐ˜๋„์ฒด ์‚ฌ์—…์žฅ์—์„œ์˜ 60๊ฐœ์˜ ์ง€์—ญ์‹œ๋ฃŒ ์ธก์ • ๊ฒฐ๊ณผ, ๊ฒ€์ถœํ•œ๊ณ„ ์ดํ•˜๋กœ ๋ถ„์„๋˜์–ด ์ œ์•ˆ๋œ ๊ด€๋ฆฌ๊ธฐ์ค€ ์ดํ•˜์˜€๋‹ค.๊ฒฐ๋ก : PGMEA, Ethyl lactate์— ๋Œ€ํ•ด EU REACH TGD์— ์˜ํ•œ ํก์ž… DNELs ๋ฐ ์‚ฐ์—…์•ˆ์ „๋ณด๊ฑด๊ณต๋‹จ์—์„œ ์ œ์‹œํ•œ RfCwork ๋ฅผ ํ™œ์šฉํ•œ ๊ด€๋ฆฌ๊ธฐ์ค€ ์ œ์•ˆ์ด ์ ์ •ํ•จ์„ ํ™•์ธํ•˜์˜€๋‹ค.ope

    ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€ ์ œ์•ˆ ๋ฐ ๋…ธ์ถœํ‰๊ฐ€ : propylene glycol monomethyl ether acetate, ethyl lactate

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    ์‚ฐ์—…๋ณด๊ฑด์ „๊ณต/์„์‚ฌ์—ฐ๊ตฌ๋ชฉ์ : ๋ณธ ์—ฐ๊ตฌ๋Š” ๋ฐ˜๋„์ฒด ์ œ์กฐ๊ณต์ •์—์„œ ํฌํ† ๋ ˆ์ง€์ŠคํŠธ ์œ ๊ธฐ์šฉ๋งค๋กœ ๊ด‘๋ฒ”์œ„ํ•˜๊ฒŒ ์‚ฌ์šฉ๋˜๋‚˜ ๊ตญ๋‚ด ์ž‘์—…ํ™˜๊ฒฝ ๋…ธ์ถœ๊ธฐ์ค€์ด ์—†๋Š” PGMEA, ์ –์‚ฐ ์—ํ‹ธ(Ethyl lactate)์— ๋Œ€ํ•ด ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€์„ ์„ค์ •ํ•˜๊ณ , ์ทจ๊ธ‰ ์‚ฌ์—…์žฅ์˜ ์‹คํƒœ ์กฐ์‚ฌ๋ฅผ ํ†ตํ•ด ์ œ์•ˆ๋œ ๊ธฐ์ค€๊ณผ ์ž‘์—…ํ™˜๊ฒฝ ๊ด€๋ฆฌ ์ˆ˜์ค€์„ ์•Œ์•„๋ณด๊ณ ์ž ํ•˜์˜€๋‹ค.์—ฐ๊ตฌ๋Œ€์ƒ ๋ฐ ๋ฐฉ๋ฒ•: ๊ด€๋ฆฌ๊ธฐ์ค€ ์„ค์ • ๋ฐฉ๋ฒ•์œผ๋กœ REACH TGD ๋ฐ ECETOC TRA์— ์˜ํ•œ EU DNELs, EPA RfC, ์‚ฐ์—…์•ˆ์ „๋ณด๊ฑด๊ณต๋‹จ์—์„œ ์ œ์‹œํ•œ RfCwork ๋“ฑ์„ ์‚ฌ์šฉํ•˜์˜€๋‹ค. PGMEA, ์ –์‚ฐ ์—ํ‹ธ๊ณผ ์œ ์‚ฌํ•œ ํŠน์„ฑ์„ ๊ฐ€์ง€๋ฉฐ, ๋…ธ์ถœ๊ธฐ์ค€์ด ์žˆ๋Š” 2-ethoxyethyl acetate, n-butyl lactate๋ฅผ ๋Œ€์ƒ์œผ๋กœ ํ•œ ํ‰๊ฐ€๊ธฐ๋ฒ• ๊ฒ€์ •์„ ํ†ตํ•ด ๋„์ถœ๋œ ๋ฐฉ๋ฒ•์„ ์ ์šฉํ•˜์—ฌ ์ง์—…์  ๊ด€๋ฆฌ๊ธฐ์ค€์„ ์ œ์•ˆํ•˜๊ณ , ํ•œ ๋ฐ˜๋„์ฒด ์‚ฌ์—…์žฅ์—์„œ ๋…ธ์ถœํ‰๊ฐ€๋ฅผ ์ˆ˜ํ–‰ํ•˜์˜€๋‹ค.์—ฐ๊ตฌ๊ฒฐ๊ณผ: ECETOC TRA์— ์˜ํ•œ ํก์ž… DNELs์€ ๊ทœ์ œ์ˆ˜์ค€์˜ 20%๋ฅผ ์ดˆ๊ณผํ•œ ๊ฐ’์„ ๋‚˜ํƒ€๋‚ด์—ˆ๊ณ , EPA RfC ๋ฐฉ๋ฒ•์€ ๊ทผ๋กœ์ž ๋…ธ์ถœ์กฐ๊ฑด์— ์ ํ•ฉํ•˜์ง€ ์•Š์•„ ์ œ์™ธํ•˜์˜€๋‹ค. ๋”ฐ๋ผ์„œ PGMEA, Ethyl lactate์— ๋Œ€ํ•œ ๊ด€๋ฆฌ๊ธฐ์ค€์œผ๋กœ REACH TGD์— ์˜ํ•œ ์ž‘์—…์ž ํก์ž… DNELs์™€ ๊ตญ๋‚ด RfCwork์˜ ๋ฒ”์œ„๊ฐ’์ธ 6.75mg/ใŽฅ(1.25ppm) ~ 21.7mg/ใŽฅ(4ppm) ๋ฐ 0.38mg/ใŽฅ(0.17ppm) ~ 5.36mg/ใŽฅ(1.1ppm)์œผ๋กœ ์„ค์ •ํ•˜์˜€๋‹ค. ์ด์— ์ž‘์—…ํ™˜๊ฒฝ์ธก์ • ๊ฒ€์ถœํ•œ๊ณ„๊ฐ’์„ ๊ณ ๋ คํ•˜์—ฌ ๊ด€๋ฆฌ๊ธฐ์ค€์€ 4ppm, 1.1ppm ์ดํ•˜๋กœ ์ œ์•ˆํ•˜์˜€๋‹ค. ๊ทธ๋ฆฌ๊ณ  ํ•œ ๋ฐ˜๋„์ฒด ์‚ฌ์—…์žฅ์—์„œ์˜ 60๊ฐœ์˜ ์ง€์—ญ์‹œ๋ฃŒ ์ธก์ • ๊ฒฐ๊ณผ, ๊ฒ€์ถœํ•œ๊ณ„ ์ดํ•˜๋กœ ๋ถ„์„๋˜์–ด ์ œ์•ˆ๋œ ๊ด€๋ฆฌ๊ธฐ์ค€ ์ดํ•˜์˜€๋‹ค.๊ฒฐ๋ก : PGMEA, Ethyl lactate์— ๋Œ€ํ•ด EU REACH TGD์— ์˜ํ•œ ํก์ž… DNELs ๋ฐ ์‚ฐ์—…์•ˆ์ „๋ณด๊ฑด๊ณต๋‹จ์—์„œ ์ œ์‹œํ•œ RfCwork ๋ฅผ ํ™œ์šฉํ•œ ๊ด€๋ฆฌ๊ธฐ์ค€ ์ œ์•ˆ์ด ์ ์ •ํ•จ์„ ํ™•์ธํ•˜์˜€๋‹ค.ope

    Usefulness of Quantitative Voxel-based Morphometry of MRI and FDG-PET in detection of Focal Cortical Dysplasia

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์ž์—ฐ๊ณผํ•™๋Œ€ํ•™ ๋‡Œ์ธ์ง€๊ณผํ•™๊ณผ, 2018. 2. ์ •์ฒœ๊ธฐ.Its important to detect the epileptogenic lesion in pre-surgical evaluation for refractory epilepsy surgery, since non-lesional epilepsy is known as a predictor of surgical failure. Focal Cortical Dysplasia (FCD) constitutes the most common non-lesional epilepsy. Voxel-based morphometry (VBM) of MRI has been useful in enhancing visualization of FCD compared to the conventional visual analysis. However, previous studies were based on qualitative methods to localize the lesion prone to subjectivity, depending on person. Thus, we investigated the usefulness of applying thresholds quantitatively through VBM of MR T1 and T2-weighted image in objective way rather than subjective method. Also, T1-weighted image and T2-weighted image are known to be sensitive to different structural information, since they have different relaxation time and echo time. Moreover, FDG-PET detects the metabolic abnormality of FCD as a hypometabolic lesion, while MRI detects FCD structural abnormality. As different modalities have different sensitivities of various FCD characteristics, multimodal analysis in diagnosis may improve detection sensitivity of neuronal disease. As a result, we investigated additive values of combining quantitative voxel-based analysis of T1-weighted image, T2-weighted image and FDG-PET in FCD detection. 55 patients who underwent epilepsy surgery and histologically proven as FCD between 2004 and 2016 (30 female, mean age at MRI 29.5 years, range 16-55 years) at Seoul National University Hospital were retrospectively recruited. Preoperative T1, T2 MRIs and FDG-PET were analyzed with voxel-based methods in SPM 12, Matlab. The gray-white matter junction of each patient was extracted and compared to those from healthy controls (26 subjects including 14 female, mean age at MRI 33 years, range 23-45 years). Thereafter, the junction image was made to highlight the blurred gray-white matter. Two observers chose potential lesion in each junction image, which made the blurred region stand out. For quantitative analysis, we applied threshold and among the over-threshold clusters, the 3 clusters with maximum size of voxels were selected as candidates of the lesion. FDG-PET data were compared to those in 50 normal controls (37.8 years), using two sample t-test (p<0.001). Among the clusters over the threshold, the area with maximum standard deviation was selected as a candidate lesion. The area chosen in MRI and PET analysis was compared with the area surgically resected on post-operative MRIs, taking the surgical outcome into account. Out of 46 patients whose seizure control after the surgery showed improvement, visual assessment alone in MRIs detected FCD in 16 patients. However, by voxel-based analysis, the FCD lesions were found in 21 patients. Furthermore, when conventional method and voxel-based method were combined, FCD lesions were detected in 26 patients with MRI T1 and T2-weighted image. Consideration of MRI and PET images together detected 30 patients lesion correctly, while MRI alone detected 26 patients lesion with combination of conventional visual analysis and voxel-based morphometric method. Furthermore, the more concordant suspected lesion in between the modalities, the better the surgical outcome presented. There were no significant differences in sensitivity concerning the gender, age at surgery and scanners difference respectively. Our results suggest that voxel based analysis based on the blurring of gray and white matter junction not only helps visualization qualitatively, but also can be used quantitatively additional to the conventional visual analysis (p<0.000). Also, consideration of both MRI and PET leads better detection of FCD with good surgical outcome.1. Introduction 1 2. Materials and Methods 83 3. Results 9 4. Discussion 15 5. Conclusion 22 References 23 List of Tables 25 List of Figures 28 Abstract in Korean 38Maste

    Reconstruction of changes in eolian particle deposition across the Mid-Pleistocene Transition in the north central Pacific

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    We investigated flux, grain size distribution, Nd-Sr isotope composition, mineral composition, and trace metal composition (REEs and Sc) of inorganic silicate fraction (ISF, mainly Asian dust with an unrestricted amount of volcanic materials) deposited during 600 ~ 1000 ka across the Mid-Pleistocene Transition at core NPGP 1401-2A (32ยฐ01'N, 178ยฐ59'E, 5205m) taken from the central part of the North Pacific. Our results reveal about a 2-fold increase in ISF flux after 800 ka, which is associated with an increase in La/Sc and a decrease in mean grain size. Asian dusts are finer than volcanic materials and La/Sc increases with the enhanced contribution of Asian dusts. Thus, increased flux after 800 ka can be explained by the increased contribution of Asian dusts relative to volcanic materials, likely due to an intensified Westerly Jet (WJ) and the drying of the Asian continent after the MPT. Mean grain size of ISF varies systematically in relation to glacial-interglacial cycles with a decrease during glacial stages, which is consistent with the previous results in the study area. Such a cyclical pattern is also attributed to the increase in the relative contribution of Asian dusts over volcanic components in glacial stages due to intensified WJ and drying of the Asian continent. Thus, it can be concluded that climate changes that had occurred across the MPT were similar to those of interglacial to glacial transitions at least in terms of the dust budget. Different from the Shatsky Rise, however, compositional changes associated with glacial-interglacial mean grain size fluctuations are not observed in Nd-Sr isotope ratios and trace element composition in our study of the Hess Rise. This may be attributed to the location of the study site far (>4,000 km) from the volcanic sources. The volcanic component at the study site comprises less than 10% and varies within 3% over glacial-interglacial cycles. Such a small variation was not enough to imprint geochemical signals.๋ชฉ ์ฐจ List of Tables โ…ณ List of Figures โ…ด List of Appendix โ…ถ Abstract โ…ท 1. ์„œ ๋ก  1 2. ์—ฐ๊ตฌ ๋ฐฉ๋ฒ• 2.1 ์—ฐ๊ตฌ ์ง€์—ญ ๋ฐ ์‹œ๋ฃŒ 4 2.2 ๋ฌด๊ธฐ๊ทœ์‚ฐ์—ผ๊ด‘๋ฌผ์˜ ์ถ”์ถœ 7 2.2.1 ์„ธ๋ฆฝ์ž ๋ถ„๋ฆฌ 7 2.2.2 ํƒ„์‚ฐ์—ผ ์ œ๊ฑฐ 7 2.2.3 ์‚ฐํ™”/์ˆ˜์‚ฐํ™”๋ฌผ ์ œ๊ฑฐ 7 2.2.4 ์ƒ๋ฌผ๊ธฐ์› ๊ทœ์‚ฐ์—ผ ์ œ๊ฑฐ 8 2.3 ๋ฌด๊ธฐ๊ทœ์‚ฐ์—ผ๊ด‘๋ฌผ์˜ ํ”Œ๋Ÿญ์Šค ๊ณ„์‚ฐ 8 2.4 ์ž…๋„ ๋ถ„์„ 8 2.5 ์ง€ํ™”ํ•™ ๋ถ„์„ 9 2.6 ์ ํ† ๊ด‘๋ฌผ ๋ถ„์„ 10 2.7 ๋™์œ„์›์†Œ ๋ถ„์„ 10 3. ๊ฒฐ๊ณผ 11 4. ํ† ์˜ 4.1 ๋น™ํ•˜๊ธฐ/๊ฐ„๋น™๊ธฐ ์ž…๋„ ๋ณ€ํ™”์˜ ์›์ธ 21 4.1.1 ์ค‘์•™ํƒœํ‰์–‘์—์„œ ๋ฐœ์ƒ๋œ ๊ตญ์†Œ์  ๋Œ€๊ธฐ ์ˆœํ™˜ ๊ฐ•๋„ ๋ณ€ํ™”์— ๋”ฐ๋ฅธ ์ž…๋„ ๋ณ€ํ™” ๊ฐ€๋Šฅ์„ฑ 24 4.1.2 ์ค‘์•™ํƒœํ‰์–‘์—์„œ ์œ ์ž…๋˜๋Š” ํ’์„ฑ ํ‡ด์ ๋ฌผ ์ž…์ž์˜ ์ค‘๊ตญ ๋‚ด ๊ธฐ์›์ง€ ๋ณ€ํ™” ๊ฐ€๋Šฅ์„ฑ 24 4.1.1 ์ค‘์•™ํƒœํ‰์–‘ ํ™”์‚ฐ๊ธฐ์› ๋ฌผ์งˆ ์œ ์ž…์˜ ๊ฐ€๋Šฅ์„ฑ 28 4.2 MPT ์‹œ๊ธฐ ์ค‘์•™ํƒœํ‰์–‘์—์„œ ์ผ์–ด๋‚œ ๋Œ€๊ธฐ ํ™˜๊ฒฝ ๋ณ€ํ™” 32 5. ๊ฒฐ๋ก  35 ์ฐธ๊ณ ๋ฌธํ—Œ 37 ๋ถ€๋ก A 42 ๊ฐ์‚ฌ์˜ ๊ธ€ 73Maste

    Impaired Social and Role Function in Ultra-High Risk for Psychosis and First-Episode Schizophrenia: Its Relations with Negative Symptoms

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    OBJECTIVE: Psychosocial dysfunction was a nettlesome of schizophrenia even in their prodromal phase as well as first episode and its relations with psychopathology were not determined. The aim of the present study was to examine whether the social and role function impairment was found in ultra-high risk for psychosis (UHR) individuals as well as first-episode schizophrenia patients and to explore its relations with psychopathology. METHODS: Thirty-seven normal controls, 63 UHR participants and 28 young, first-episode schizophrenia patients were recruited. Psychosocial functioning was examined by using Global function: Social and Role scale. Psychopathologies of positive, negative and depressive symptom were also measured. RESULTS: Social and role functioning in UHR were compromised at the equivalent level of those of first-episode schizophrenia patients. Multiple linear regression analysis revealed that social and role dysfunction was associated with negative symptoms in each UHR and first-episode schizophrenia group. CONCLUSION: These findings suggest that the significant impairment of social and role function may be appeared before the active psychosis onset at the level of extent to those of first-episode schizophrenia patients. The psychosocial intervention strategy especially targeting the negative symptoms should be developed and provided to individuals from their prepsychotic stage of schizophrenia.ope

    Pharmacokinetic-pharmacodynamic modeling and simulation study for exploration of optimal dosage regimens for low-dose aspirin therapy in Koreans

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ) --์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์˜ํ•™๊ณผ (์•ฝ๋ฆฌํ•™์ „๊ณต),2009.2.Maste

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์Œ์•…ํ•™๊ณผ ์ž‘๊ณก์ „๊ณต,2002.Maste

    ์„œ์ง€๋งˆ ์‹œ์˜ ์ƒ์ƒ์„ธ๊ณ„ ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ(์„์‚ฌ)--์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› :์ค‘์–ด์ค‘๋ฌธํ•™๊ณผ ๋ฌธํ•™์ „๊ณต,2003.Maste

    ์ •์ƒ์ธ 24์‹œ๊ฐ„ ์œ„ ์‚ฐ๋„์˜ ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ๋ง์„ ์ด์šฉํ•œ ์œ„์‚ฐ๋ถ„๋น„์–ต์ œ์ œ์˜ ํšจ๋Šฅ ํ‰๊ฐ€ ๋ฐฉ๋ฒ•๋ก  ์—ฐ๊ตฌ

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    ํ•™์œ„๋…ผ๋ฌธ (๋ฐ•์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์˜ํ•™๊ณผ ์•ฝ๋ฆฌํ•™ ์ „๊ณต, 2012. 8. ์žฅ์ธ์ง„.์œ„์‹๋„ ์—ญ๋ฅ˜์„ฑ ์งˆํ™˜ (Gastroesophageal Reflux Disease, GERD)์„ ๋น„๋กฏํ•œ ์œ„์‚ฐ ๋ถ„๋น„์™€ ๊ด€๋ จ๋œ ์งˆํ™˜์— ๋„๋ฆฌ ์‚ฌ์šฉ๋˜๋Š” proton pump inhibitor (PPI) ๊ณ„์—ด ์•ฝ๋ฌผ์˜ ๋‹จ์ ์„ ๊ทน๋ณตํ•˜๋Š” ์ƒˆ๋กœ์šด ๊ณ„์—ด์˜ ์œ„์‚ฐ๋ถ„๋น„ ์–ต์ œ์ œ๋กœ์„œ potassium-competitive acid blocker (P-CAB)๊ฐ€ ๋Œ€๋‘๋˜๊ณ  ์žˆ๋‹ค. ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” ์ƒˆ๋กญ๊ฒŒ ๊ฐœ๋ฐœ๋œ P-CAB ๊ณ„์—ด ์•ฝ๋ฌผ์ธ YH4808์˜ 1์ƒ ์—ฐ๊ตฌ ์ž๋ฃŒ๋ฅผ ํ™œ์šฉํ•œ ๋ชจ๋ธ๋ง ๋ฐ ์‹œ๋ฎฌ๋ ˆ์ด์…˜์„ ํ†ตํ•ด ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์„ ์ˆ˜๋ฆฝํ•˜๊ณ  ์ตœ์ ์˜ ์šฉ๋Ÿ‰์šฉ๋ฒ•์„ ํƒ์ƒ‰ํ•˜๊ณ ์ž ํ•˜์˜€๋‹ค. ์ž„์ƒ์—ฐ๊ตฌ๋ฅผ ์™„๋ฃŒํ•œ ํ”ผํ—˜์ž๋“ค ์ค‘ YH4808์„ ํˆฌ์—ฌ๋ฐ›์€ 79๋ช…์˜ ํ”ผํ—˜์ž์˜ ํ˜ˆ์ค‘ ๋†๋„ ๋ฐ ์ฑ„ํ˜ˆ ์‹œ๊ฐ„ ์ž๋ฃŒ์™€ ์œ„์•ฝ ๋˜๋Š” YH4808์„ ํˆฌ์—ฌ๋ฐ›์€ ํ”ผํ—˜์ž ์ค‘ Helicobactor pylori ์Œ์„ฑ์ด๋ฉด์„œ 24์‹œ๊ฐ„ ์œ„ ๋‚ด pH ๋ชจ๋‹ˆํ„ฐ๋ง์ด ์ ์ ˆํ•˜๊ฒŒ ์ˆ˜ํ–‰๋œ 71๋ช…์˜ ์ž๋ฃŒ๋กœ ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์„ NONMEM 7 (Level 1.2)์„ ์ด์šฉํ•˜์—ฌ ์ˆ˜๋ฆฝํ•˜์˜€๋‹ค. ์•ฝ๋™ํ•™ ๋ชจ๋ธ๊ณผ ๊ธฐ์ €์น˜ ๋ชจ๋ธ์„ ๋จผ์ € ์ˆ˜๋ฆฝํ•œ ํ›„ ๊ฐœ๋ณ„ ํŒŒ๋ผ๋ฏธํ„ฐ๋ฅผ ๊ณ ์ •ํ•˜์—ฌ ์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์„ ์ˆ˜๋ฆฝํ•˜๋Š” ์ˆœ์ฐจ์  ๋ถ„์„์„ ์‹ค์‹œํ•˜์˜€๋‹ค. YH4808์˜ ์•ฝ๋™ํ•™ ๋ชจ๋ธ์€ ํก์ˆ˜ ์ง€์—ฐ ์‹œ๊ฐ„์ด ์žˆ๋Š” 1์ฐจ ํก์ˆ˜ ๋ฐ 1์ฐจ ์†Œ์‹ค์„ ๋”ฐ๋ฅด๋Š” 2๊ตฌํš ๋ชจ๋ธ์ด ์„ ์ •๋˜์—ˆ์œผ๋ฉฐ, ์‹ํ›„ ํˆฌ์—ฌ์‹œ ์Œ์‹๋ฌผ์— ์˜ํ•˜์—ฌ ์ฒด๋‚ด ํก์ˆ˜๊ฐ€ 3.2๋ฐฐ ์ฆ๊ฐ€ํ•˜์˜€๋‹ค. ์œ„ ๋‚ด pH์˜ ๊ธฐ์ €์น˜ ๋ชจ๋ธ์—๋Š” ๊ฐ„์ ‘ ํšจ๊ณผ ๋ชจ๋ธ(indirect response model)์„ ๊ธฐ๋ณธ์œผ๋กœ ์‹์‚ฌ์˜ ์˜ํ–ฅ์™€ ์ผ์ฃผ ๋ณ€ํ™” ์˜ํ–ฅ์„ ๋ฐ˜์˜ํ•˜์˜€์œผ๋ฉฐ, ์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์€ ์œ„ ๋‚ด pH๊ฐ€ ์ฆ๊ฐ€ ์†๋„๊ฐ€ ์•ฝ๋ฌผ ๋†๋„์— ๋Œ€ํ•ด Emax ๋ชจ๋ธ์„ ๋”ฐ๋ผ ์˜ํ–ฅ์„ ๋ฐ›๋„๋ก ์ˆ˜๋ฆฝํ•˜์˜€๋‹ค. ๋ชจ๋ธ ํ‰๊ฐ€ ๊ฒฐ๊ณผ, ๊ตฌ์ถ•๋œ ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์€ ์‹ค์ œ ์ž„์ƒ์‹œํ—˜ ๊ฒฐ๊ณผ๋ฅผ ๋น„๊ต์  ์ž˜ ๋ฐ˜์˜ํ•˜์˜€๋‹ค. ์ˆ˜๋ฆฝ๋œ ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ๋กœ ์ตœ์  ์šฉ๋Ÿ‰์šฉ๋ฒ•์„ ํƒ์ƒ‰ํ•˜๊ธฐ ์œ„ํ•˜์—ฌ YH4808 ์น˜๋ฃŒ ์šฉ๋Ÿ‰์„ 1์ผ 200 mg์œผ๋กœ ๊ฐ€์ •ํ•˜๊ณ , ์‹ํ›„ ๋˜๋Š” ์‹์ „ ํˆฌ์—ฌ ๋ฐ 1์ผ 1ํšŒ ์šฉ๋ฒ• ๋˜๋Š” 1์ผ 2ํšŒ ์šฉ๋ฒ•์„ ์ ์šฉํ•˜์—ฌ ์œ„ ๋‚ด pH ๋ฅผ ์‹œ๋ฎฌ๋ ˆ์ด์…˜ํ•˜์˜€๋‹ค. ๊ทธ ๊ฒฐ๊ณผ, ์‹์ „ ํˆฌ์—ฌ์— ๋น„ํ•ด ์‹ํ›„ ํˆฌ์—ฌ์‹œ pH >4 ์œ ์ง€์‹œ๊ฐ„ ๋น„์œจ์ด ์•ฝ 20% ๋†’์•˜์œผ๋ฉฐ, 1์ผ 2ํšŒ ํˆฌ์—ฌ์‹œ 1์ผ 1ํšŒ ํˆฌ์—ฌ์— ๋น„ํ•ด ์•ผ๊ฐ„ pH > 4 ์œ ์ง€์‹œ๊ฐ„ ๋น„์œจ์ด ์•ฝ 12% ๋†’์•˜๋‹ค. 1์ผ 2ํšŒ ์šฉ๋ฒ•์‹œ 1ํšŒ 1ํšŒ ์šฉ๋ฒ•์— ๋น„ํ•ด ๋ณต์šฉํŽธ๋ฆฌ์„ฑ์ด ํฌ๊ฒŒ ๊ฐ์†Œํ•˜๋Š” ๋ฐ ๋น„ํ•˜์—ฌ ์œ„ ๋‚ด pH ์ƒ์Šน ํšจ๊ณผ๋Š” 1์ผ 1ํšŒ ์šฉ๋ฒ•์— ๋น„ํ•ด ํฐ ์ฐจ์ด๊ฐ€ ์—†์—ˆ๋‹ค. ๊ฒฐ๋ก ์ ์œผ๋กœ, ๋ณธ ์—ฐ๊ตฌ์—์„œ๋Š” 24์‹œ๊ฐ„ ์œ„ ๋‚ด pH ๋ชจ๋‹ˆํ„ฐ๋ง ์ž๋ฃŒ๋ฅผ ์ด์šฉํ•˜์—ฌ P-CAB ๊ณ„์—ด ์•ฝ๋ฌผ์ธ YH4808์˜ ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ์„ ์ˆ˜๋ฆฝํ•˜์˜€์œผ๋ฉฐ, ์ž„์ƒ์‹œํ—˜ ์‹œ๋ฎฌ๋ ˆ์ด์…˜์„ ํ†ตํ•ด ์ตœ์  ์šฉ๋Ÿ‰์šฉ๋ฒ•์„ ์ œ์‹œํ•˜์˜€๋‹ค.์ดˆ ๋ก 1 ๋ชฉ ์ฐจ 3 List of Tables 3 List of Figures 4 List of abbreviations and symbols 7 ์„œ ๋ก  9 ์—ฐ๊ตฌ๋ฐฉ๋ฒ• 12 1. ์ž„์ƒ์—ฐ๊ตฌ 12 2. ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ๋ง 18 ์—ฐ๊ตฌ๊ฒฐ๊ณผ 21 1. ๋Œ€์ƒ ์ž๋ฃŒ 21 2. ์•ฝ๋™ํ•™ ๋ชจ๋ธ๋ง 25 3. ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ๋ง 34 A. ์œ„ ๋‚ด pH ๊ธฐ์ €์น˜ ๋ชจ๋ธ 37 B. ์•ฝ๋™-์•ฝ๋ ฅํ•™ ๋ชจ๋ธ 43 4. ์‹œ๋ฎฌ๋ ˆ์ด์…˜ 50 ๊ณ ์ฐฐ ๋ฐ ๊ฒฐ๋ก  55 ์ฐธ๊ณ ๋ฌธํ—Œ 58 ๋ถ€ ๋ก 61Docto

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    ํ•™์œ„๋…ผ๋ฌธ (์„์‚ฌ)-- ์„œ์šธ๋Œ€ํ•™๊ต ๋Œ€ํ•™์› : ์ˆ˜ํ•™๊ต์œก๊ณผ, 2015. 8. ๊น€์„œ๋ น.In this thesis, we study the (i,j)-step competition graph of an oriented complete bipartite graph. Kim et al. studied the competition graph of an oriented complete bipartite graph. We take a further step to study the (1,2)-step competition graph of an oriented complete bipartite graph by extending the results given by Kim et al. Then we study (i,j)-step competition graph, a more general version of (1,2)-step competition graph. Finally, we deal with the limit of (i,j)-step competition graph.Abstract 1 Introduction 1.1 The notion of (1,2)-step competition graphs 1.2 The competition graphs of oriented complete bipartite graphs 1.3 A preview of thesis 1.4 (i,j)-step competition graphs 2 (1,2)-step competition graphs 2.1 A characterization of (1,2)-step competition graphs 2.2 Structural characterization of (1,2)-step competition graphs 2.3 Extremal (1,2)-step competition graphs 3 (i,j)-step competition graphs 4 Closing remarks Abstract(in Korean)Maste
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