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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 劉興華 | |
| dc.contributor.author | Wei-Che Chiang | en |
| dc.contributor.author | 江維哲 | zh_TW |
| dc.date.accessioned | 2021-06-16T06:43:20Z | - |
| dc.date.available | 2015-10-09 | |
| dc.date.copyright | 2014-10-09 | |
| dc.date.issued | 2014 | |
| dc.date.submitted | 2014-07-28 | |
| dc.identifier.citation | 1. Bizzari S., Oppenberg B., and Iskikawa Y. 2000. Plasticizers. Chemical economics handbook. Palo Alto, CA: SRI International.
2. Heudorf U., Mersch-Sundermann V., and Angerer J. 2007. Phthalates: Toxicology and exposure. Int. J. Hyg. Environ. Health 210:623–634. 3. Hanawa T., Muramatsu E., Asakawa K., Suzuki M., Tanaka M., Kawano K., Seki T., Juni K., Nakajima S. 2000. Investigation of the release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing for intravenous administration. Int J Pharm. 210 (1-2):109-15. 4. Craig S.B., Bhatt U.H., Patel K. 1997. Stability and compatibility of topotecan hydrochloride for injection with common infusion solutions and containers. J. Pharm. Biomed. Anal. 16, 199–205. 5. Nuijen B., Bouma M., Henrar R.E., Manada C., Bult A., Bejen J.H. 1999. Compartibility and stability of aplidine, a novel marine derived depsipeptide antitumor agent, in infusion devices, and its hemolytic and precipitation potential upon i.v. administration. Anti-Cancer Drugs 10, 879–887. 6. Takehisa H., Naoko E., Masahiko S., Katsuhide T., Moriyuki O., Keizoh S., Mutsuko T., Kenji K., Shin'ichiro N., Toshio O. 2005. Release behavior of diethylhexyl phthalate from the polyvinyl-chloride tubing used for intravenous administration and the plasticized PVC membrane. Int J Pharm. 297(1-2): 30-7. Epub. 7. Nakajima S., Kawano K., Nakazawa K. 1985. Loss of isosorbide dinitrate from solutions in administration set. Yakuzaigaku 45, 285–290. 8. Nakazawa K., Kawano K., Ito M., Amemiya H., Nakajima S. 1988. The effect of pH in the solutions on the absorption of cinnamic acid into the administration set. Yakugaku Zasshi 108, 1110–1113. 9. Lyche JL., Gutleb AC., Bergman A., Eriksen GS., Murk AJ., Ropstad E., Saunders M., Skaare JU. 2009. Reproductive and developmental toxicity of phthalates. J Toxicol Environ Health B Crit Rev.12(4):225-49. 10. Koo H. J., and Lee B. M. 2004. Estimated exposure to phthalates in cosmetics and risk assessment. J. Toxicol. Environ. Health A 67:1901–1914. 11. Kavlock R., Barr D., Boekelheide K., Breslin W., Breysse P., Chapin R., Gaido K., Hodgson E., Marcus M., Shea K., and Williams P. 2006. NTP-CERHR Expert Panel update on the reproductive and developmental toxicity of di (2-ethylhexyl) phthalate. Reprod. Toxicol. 22:291–399. 12. Calafat AM., Needham LL., Silva MJ., Lambert G. 2004. Exposure to di-(2-ethylhexyl) phthalate among premature neonates in a neonatal intensive care unit. Pediatrics. 113(5):e429-34. 13. Kavlock R., Boekelheide K., Chapin R., Cunningham M., Faustman E., Foster P., Golub M., Henderson R., Hinberg I., Little R.,Seed J., Shea K., Tabacoba S., Tyl R., Williams P., and Zacharewski T. 2002. NTP Center for the evaluation of risks to human reproduction; Phthalates expert panel report on the reproductive and developmental toxicity of di(2-ethylhexyl)phthalate. Reprod. Toxicol. 16:529–653. 14. Ito, Y., Yokota, H., Wang, R., Yamanoshita, O., Ichihara, G., Wang, H., Kurata, Y., Takagi, K., and Nakajima, T. 2005. Species differences in the metabolism of di(2-ethylhexyl) phthalate (DEHP) in several organs of mice, rats, and marmosets. Arch. Toxicol. 79:147–154. 15. Peck, C. C., and Albro, P. W. 1982. Toxic potential of the plasticizer di(2-ethylhexyl) phthalate in the context of its disposition and metabolism in primates and man. Environ. Health Perspect. 45:11–17. 16. Cresteil, T. 1998. Onset of xenobiotic metabolism in children: toxicological implications. Food Addit. Contam. 15(suppl.):45–51. 17. Koch, H. M., Preuss, R., and Angerer, J. 2006. Di(2-ethylhexyl)phthalate (DEHP): Human metabolism and internal exposure—An update and latest results. Int. J. Androl. 29:155–165. 18. Lorber M., Angerer J., Koch HM. 2010. A simple pharmacokinetic model to characterize exposure of Americans to di-2-ethylhexyl phthalate. J Expo Sci Environ Epidemiol. 20 (1): 38-53. 19. Koch, H. M., Bolt, H. M., Preuss, R., and Angerer, J. 2005a. New metabolites of di(2-ethylhexyl)phthalate (DEHP) in human urine and serum after single oral doses of deuterium-labelled DEHP. Arch. Toxicol. 79:367–376. 20. Lottrup, G., Andersson, A. M., Leffers, H., Mortensen, G. K., Toppari, J., Skakkebaek, N. E., and Main, K. M. 2006. Possible impact of phthalates on infant reproductive health. Int. J. Androl. 29:172–180; discussion 181–185. 21. Main, K. M., Mortensen, G. K., Kaleva, M. M., Boisen, K. A., Damgaard, I. N., Chellakooty, M., Schmidt, I. M., Suomi, A. M., Virtanen, H. E., Petersen, D. V., Andersson, A. M., Toppari, J., and Skakkebaek, N. E. 2006. Human breast milk contamination with phthalates and alterations of endogenous reproductive hormones in three months old infants. Environ. Health Perspect. 114:270–276. 22. Zhu, J., Phillips, S. P., Feng, Y. L., and Yang, X. 2006. Phthalate esters in human milk: concentration variations over 6-month postpartum time. Environ. Sci. Technol. 40:5276–5281. 23. Silva, M. J., Reidy, J. A., Herbert, A. R., Preau, J. L., Needham, L. L., and Calafat, A. M. 2004b. Detection of phthalate metabolites in human amniotic fluid. Bull. Environ. Contam. Toxicol. 72:1226–1231. 24. Latini, G., De Felice, C., Presta, G., Del Vecchio, A., Paris, I., Ruggieri, F., and Mazzeo, P. 2003. In utero exposure to di-(2-ethylhexyl) phthalate and duration of human pregnancy. Environ. Health Perspect. 111:1783–1785. 25. Lovekamp-Swan T., Davis BJ. 2003. Mechanisms of Phthalate Ester Toxicity in the Female Reproductive System. Environ Health Perspect. 111(2):139-45. 26. Grande SW., Andrade AJ., Talsness CE., Grote K., Chahoud I. 2006. A dose-response study following in utero and lactational exposure to di(2-ethylhexyl)phthalate: effects on female rat reproductive development. Toxicol Sci. 91(1):247-54. 27. Andrade AJ., Grande SW., Talsness CE., Gericke C., Grote K., Golombiewski A., Sterner-Kock A., Chahoud I. 2006. A dose response study following in utero and lactational exposure to di-(2-ethylhexyl) phthalate (DEHP): reproductive effects on adult male offspring rats. Toxicology. 228(1):85-97. 28. Ma M., Kondo T., Ban S., Umemura T., Kurahashi N., Takeda M., Kishi R. 2006. Exposure of prepubertal female rats to inhaled di(2-ethylhexyl)phthalate affects the onset of puberty and postpubertal reproductive functions. Toxicol Sci. 93(1):164-71. 29. Beko G., Weschler CJ., Langer S., Callesen M., Toftum J., Clausen G. 2013. Children's phthalate intakes and resultant cumulative exposures estimated from urine compared with estimates from dust ingestion, inhalation and dermal absorption in their homes and daycare centers. PLoS One. 8(4):e62442. 30. Zhang Y., Lin L., Cao Y., Chen B., Zheng L., Ge RS. 2009. Phthalate levels and low birth weight: a nested case-control study of Chinese newborns. J Pediatr. 155(4): 500-4. 31. Lucas A. 1991. Programming by early nutrition in man. Ciba Found Symp 156:38 – 50 32. Vaag A., Jensen CB., Poulsen P., Brons C., Pilgaard K., Grunnet L., Vielwerth S., Alibegovic A. 2006. Metabolic aspects of insulin resistance in individuals born small for gestational age. Horm Res. 65(Suppl 3): 137–143 33. Phillips DI., Barker DJ., Hales CN., Hirst S., Osmond C. 1994. Thinness at birth and insulin resistance in adult life. Diabetologia 37:150–154 34. Rasmussen EL., Malis C., Jensen CB., Jensen JE., Storgaard H., Poulsen P., Pilgaard K., Schou JH., Madsbad S., Astrup A., Vaag A. 2005. Altered fat tissue distribution in young adult men who had low birth weight. Diabetes Care 28:151– 153 35. Kensara OA.,Wootton SA., Phillips DI., Patel M., Jackson AA., Elia M. 2005. Fetal programming of body composition: relation between birth weight and body composition measured with dual-energy x-ray absorptiometry and anthropometric methods in older Englishmen. Am J Clin Nutr 82:980–987 36. Jensen CB, Storgaard H, Madsbad S, Richter EA, Vaag AA. Altered skeletal muscle fiber composition and size precede whole-body insulin resistance in young men with low birth weight. 2007. J Clin Endocrinol Metab. 92(4):1530-4. 37. Weintraub H. 1993. The MyoD family and myogenesis: redundancy, networks, and thresholds. Cell 75:1241–1244. 38. Weintraub H, Davis R, Tapscott S, Thayer M, Krause M, Benezra R, et al. 1991. The myoD gene family: nodal point during specification of the muscle cell lineage. Science 251:761–766. 39. Lassar AB, Skapek SX, Novitch B. 1994. Regulatory mechanisms that coordinate skeletal muscle differentiation and cell cycle withdrawal. Curr Opin Cell Biol 6:788–794. 40. Olson EN, Perry M, Schulz RA. 1995. Regulation of muscle differentiation by the MEF2 family of MADS box transcription factors. Dev Biol 172:2–14. 41. Davie JK., Cho JH., Meadows E., Flynn JM., Knapp JR., Klein WH. 2007. Target gene selectivity of the myogenic basic helix- loop-helix transcription factor myogenin in embryonic muscle. Dev Biol. 311:650–664. 42. Myer A., Olson EN., Klein WH. 2001. MyoD cannot compensate for the absence of myogenin during skeletal muscle differentiation in murine embryonic stem cells. Dev Biol. 229:340–350. 43. Kaliman P., Vinals F., Testar X., Palacin M., Zorzano A. 1996. Phosphatidylinositol 3-kinase inhibitors block differentiation of skeletal muscle cells. J Biol Chem. 271:19146–19151. 44. Tamir Y., Bengal E. 2000. Phosphoinositide 3-kinase induces the transcriptional activity of MEF2 proteins during muscle differentiation. J Biol Chem. 275:34424– 34432. 45. Jensen CB., Martin-Gronert MS., Storgaard H., Madsbad S., Vaag A., Ozanne SE. 2008. Altered PI3-kinase/Akt signalling in skeletal muscle of young men with low birth weight. PLoS One 3:e3738 46. Yen YP., Tsai KS., Chen YW., Huang CF., Yang RS., Liu SH. 2010. Arsenic inhibits myogenic differentiation and muscle regeneration. Environ Health Perspect. 118(7):949-56. 47. Itsuki-Yoneda A., Kimoto M., Tsuji H., Hiemori M., Yamashita H. 2007. Effect of a hypolipidemic drug, di (2-ethylhexyl) phthalate, on mRNA-expression associated fatty acid and acetate metabolism in rat tissues. Biosci Biotechnol Biochem. 71(2): 414–420. 48. Reubsaet FA., Veerkamp JH., Dirven HA., Bruckwilder ML., Hashimoto T., Trijbels JM. 1990. The effect of di (ethyl- hexyl) phthalate on fatty acid oxidation and carnitine palmitoyltransferase in various rat tissues. Biochim Biophys Acta. 1047(3): 264–270. 49. Posnack NG., Swift LM., Kay MW., Lee NH., Sarvazyan N. 2012. Phthalate exposure changes the metabolic profile of cardiac muscle cells. Environ Health Perspect. 120(9): 1243-51. 50. Yamauchi T., Kamon J., Minokoshi Y., Ito Y., Waki H., Uchida S., Yamashita S.,Noda M., Kita S., Ueki K., Eto K., Akanuma Y., Froguel P., Foufelle F., Ferre P., Carling D., Kimura S., Nagai R., Kahn BB., Kadowaki T. 2002. Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med. 8(11): 1288-95. 51. McPherron AC., Lawler AM., Lee SJ. 1997. Regulation of skeletal muscle mass in mice by a new TGF-beta superfamily member. Nature. 387: 83–90 52. Miyake M., Takahashi H., Kitagawa E., Watanabe H., Sakurada T., Aso H., Yamaguchi T. 2012. AMPK activation by AICAR inhibits myogenic differentiation and myostatin expression in cattle. Cell Tissue Res. 349(2): 615-23. 53. Otake, T., Yoshinaga, J., and Yanagisawa, Y. 2004. Exposure to phthalate esters from indoor environment. J. Expos. Anal. Environ. Epidemiol. 14:524–528. 54. Koch, H. M., Drexler, H., and Angerer, J. 2003a. An estimation of the daily intake of di(2-ethylhexyl)phthalate (DEHP) and other phthalates in the general population. Int. J. Hyg. Environ. Health. 206:77–83. 55. Koo, H. J., and Lee, B. M. 2004. Estimated exposure to phthalates in cosmetics and risk assessment. J. Toxicol. Environ. Health A. 67:1901–1914. 56. Center for Devices and Radiological Health, U.S. Food and Drug Administration. 2001. Safety assessment of di(2-ethylhexyl)phthalate (DEHP) released from PVC medical devices. 57. Hu E., Tontonoz P., Spiegelman BM. 1995. Transdifferentiation of myoblasts by the adipogenic transcription factors PPAR gamma and C/EBP alpha. Proc Natl Acad Sci U S A. 92(21): 9856-60. 58. Lassar A., Munsterberg A. 1994. Wiring diagrams: regulatory circuits and the control of skeletal myogenesis. Curr Opin Cell Biol. 6(3):432-42. 59. Buckingham M. 1992. Making muscle in mammals. Trends Genet. 8(4):144-8. 60. Tontonoz,P., Hu,E., Spiegelman,B.M. 1994. Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor. Cell. 79,1147-1156. 61. Feige JN., Gelman L., Rossi D., Zoete V., Metivier R., Tudor C., Anghel SI., Grosdidier A., Lathion C., Engelborghs Y., Michielin O., Wahli W., Desvergne B. 2007. The endocrine disruptor monoethyl-hexyl-phthalate is a selective peroxisome proliferator-activated receptor gamma modulator that promotes adipogenesis. J Biol Chem. 282(26): 19152-66. 62. Sarath Josh MK., Pradeep S., Vijayalekshmi Amma KS., Balachandran S., Abdul Jaleel UC., Doble M., Spener F., Benjamin S. 2014. Phthalates efficiently bind to human peroxisome proliferator activated receptor and retinoid X receptor α, β, γ subtypes: an in silico approach. J Appl Toxicol. 34(7): 754-65. 63. Markert C. D., M. A. Merrick, T. E. Kirby, and S. T. Devor. 2005. Nonthermal ultrasound and exercise in skeletal muscle regeneration. Arch. Phys. Med. Rehabil. 86: 1304–1310. 64. Iwata, A., S. Fuchioka, K. Hiraoka, M. Masuhara, and K. Kami. 2010. Characteristics of locomotion, muscle strength, and muscle tissue in regenerating rat skeletal muscles. Muscle Nerve. 41: 694–701. 65. Schultz, E., D. L. Jaryszak, and C. R. Valliere. 1985. Response of satellite cells to focal skeletal muscle injury. Muscle Nerve. 8: 217–222. 66. Ten Broek, R. W., S. Grefte, and J. W. Von den Hoff. 2010. Regulatory factor and cell populations involved in skeletal muscle regeneration. J. Cell. Physiol. 224:7–16. 67. Seale, P., L. A. Sabourin, A. Girgis-Gabardo, A. Mansouri, P. Gruss, and M. E. Rudnicki. 2000. Pax7 is required for the specifi- cation of myogenic satellite cells. Cell. 102: 777–786. | |
| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/57368 | - |
| dc.description.abstract | 鄰苯二甲酸二(2-乙基己基)酯(Di(2-ethylhexyl) phthalate, DEHP)為一種塑化劑,常 在環境與人體中測得其含量。DEHP 已被証實具有生殖毒性,流行病學調查指出母 體體內 DEHP 和其代謝物鄰苯二甲酸(2-乙基己基)酯(Mono (2-ethylhexyl) phthalate, MEHP)的含量與新生兒出生體重低下呈正相關,出生體重低下可能造成代謝異常 疾病,然而目前對於 DEHP 與 MEHP 造成新生兒體重低下之發育毒性之可能原因 尚未釐清。另外也有研究指出其會干擾體內血糖調控,骨骼肌為調節血糖之主要 周邊組織,DEHP 的暴露可能對骨骼肌產生胰島素抗性,導致第二型糖尿病。故本 研究欲探討 DEHP 與 MEHP 對骨骼肌母細胞分化的影響,以 C2C12 小鼠骨骼肌母 細胞分析骨骼肌胰島素抗性與出生體重低下是否與骨骼肌分化受調控造成發育不 全相關。本研究以 C2C12 於分化培養基中給予 0~1000 μM 之 DEHP 與 MEHP 持 續四天,由 MTT assay,結果顯示在 1000 μM 以下 DEHP 皆不會造成細胞死亡; 而在 100 μM 開始 MEHP 產生細胞毒性。以蘇木紫-伊紅氏染色觀察分化四天過程 持續處理0~100 μM之DEHP與MEHP,發現25 μM與10 μM開始DEHP及MEHP 會抑制骨骼肌肉細胞分化,且具劑量效應關係。用西方墨點法分析 myosin heavy chain C (MHC)、myogenin、phospho-protein kinase B (p-AKT)與 phosph- AMP-Activated Protein Kinase (p-AMPK)之表現量,發現在骨骼肌分化相關標誌蛋 白MHC、myogenin與p-AKT皆從25μM開始受抑治,且具劑量相關性;隨著DEHP 與 MEHP 劑量的增加,發現 p-AMPK 的活化增加,處理 AMPK 抑制劑—compound C (0.5 μM與 1 μM)後抑制 DEHP 與 MEHP 引發之 AMPK 磷酸化表現,發現骨骼 肌分化相關標誌表現 MHC、myogenin 與 p-AKT 皆有回升之現象;在形態方面, 以蘇木紫-伊紅染色觀察骨骼肌分化時細胞產生融合現象與肌小管(myotube)生成,發現處理 compound C 後能緩解 DEHP 與 MEHP 對骨骼肌分化所造成的抑制現象。綜合上述蛋白分析表現與形態觀察之結果,顯示在骨骼肌分化之情況暴露 DEHP 與 MEHP 後會活化 AMPK 磷酸化表現,進而負向調控 p-AKT、MHC 與 myogenin 的訊息傳遞,抑制骨骼肌分化,而代謝物 MEHP 對骨骼肌分化造成之負 面影響加劇,顯示暴露 DEHP 後經代謝可能對骨骼肌肉之分化產生更嚴重影響。 此外,在肌肉分化條件下給予 DEHP 與 MEHP 0-100 μM,發現 PPAR γ (peroxisome proliferator-activated receptor γ )表現量皆從 DEHP 與 MEHP 50 μM上升,使用油滴 染色偵測肌小管內油滴含量,發現暴露 DEHP 與 MEHP 皆使得肌小管內油滴含量 增加,分別從 DEHP 25 μM與 MEHP 10 μM開始增加。處理 compound C 後,不論 在 DEHP 100 μM或 MEHP 50 μM組別發現 PPAR γ 表現量下降,同時肌小管內油 滴量減少,顯示 AMPK 的活化與 PPAR γ 及肌小管內油滴量的調控呈正相關。動 物實驗結果顯示,口服給予三週齡 ICR 雄性小鼠 DEHP 1, 10 與 100 mg/kg 後,測 量其體重、比目魚肌、腓腸肌與脛前骨肌重發現組間並無差異,使用 rotarod 測量 小鼠肌肉之強度,同樣顯示無差異。然而,使用免疫組織染色偵測比目魚肌內衛 星細胞之相關蛋白 Pax7,發現對照組較暴露組含量多,俱劑量效應關係,顯示暴 露 DEHP 可能造成衛星細胞減少,進而導致肌肉受傷時之復原能力較差。綜合上 述,細胞實驗顯示暴露 DEHP 或 MEHP 可能經由活化 p-AMPK 抑制骨骼肌肉分化 並促進其走向脂肪細胞分化途徑,其中,又以 MEHP 所造成之影響更為劇烈。動 物實驗部分,雖然處理 DEHP 組別在肌肉重量與耐力並無改變,然而 Pax7 表現量 的減少可能表示處理組別之衛星細胞減少,顯示肌肉受傷後可能復原能力較差, 其進一步實驗有待釐清。 | zh_TW |
| dc.description.provenance | Made available in DSpace on 2021-06-16T06:43:20Z (GMT). No. of bitstreams: 1 ntu-103-R01447004-1.pdf: 13725519 bytes, checksum: b244d1f4c4df8c01c8878aedd4e6d5ce (MD5) Previous issue date: 2014 | en |
| dc.description.tableofcontents | 碩士學位論文口試委員會審定書--------------------------I<br>
誌謝-------------------------------------------------II<br> <br>中文摘要----------------------------------------III Abstract------------------------------------------------V Abbreviations-------------------------------------VIII Chapter 1: Introduction-------------------------------1 Chapter 2: Materials and Methods--------------------------11 Chapter 3: Results----------------------------------------20 Chapter 4: Discussion-------------------------------------29 Chapter 5: Figures and Figure Legends------------------- 34 Chapter 6: Conclusions and Future Perspectives----------66 Chapter 7: References----------------------------------69 | |
| dc.language.iso | en | |
| dc.subject | p-AMPK | zh_TW |
| dc.subject | 脂肪分化 | zh_TW |
| dc.subject | 骨骼肌分化 | zh_TW |
| dc.subject | 肌母細胞 | zh_TW |
| dc.subject | 鄰苯二甲酸(2-乙基己基)酯 | zh_TW |
| dc.subject | 鄰苯二甲酸二(2-乙基己基)酯 | zh_TW |
| dc.subject | Pax7 | zh_TW |
| dc.subject | p-AMPK | en |
| dc.subject | adipogenesis | en |
| dc.subject | myogenesis | en |
| dc.subject | myoblasts | en |
| dc.subject | DEHP | en |
| dc.subject | MEHP | en |
| dc.subject | pax7 | en |
| dc.title | 探討塑化劑鄰苯二甲酸二（2-乙基己基）酯及其代謝物對骨骼肌分化之影響 | zh_TW |
| dc.title | Effects of Di (2-ethylhexyl) Phthalate and Its Metabolite on Myogenic Differentiation | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 102-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蕭水銀,楊榮森,姜至剛 | |
| dc.subject.keyword | 鄰苯二甲酸二(2-乙基己基)酯,鄰苯二甲酸(2-乙基己基)酯,肌母細胞,骨骼肌分化,脂肪分化,p-AMPK,Pax7, | zh_TW |
| dc.subject.keyword | DEHP,MEHP,myoblasts,myogenesis,adipogenesis,p-AMPK,pax7, | en |
| dc.relation.page | 83 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2014-07-29 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 毒理學研究所 | zh_TW |
| 顯示於系所單位： | 毒理學研究所 | |
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