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(2010) R: A language and environment for statistical computing. R Foundation for Statistical Computing. Vienna, Austria. pp. Available at: <ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"http:\/\/www.R-project.org\/\" xlink:type=\"simple\">http:\/\/www.R-project.org\/<\/ext-link> Accessed April 2, 2012."},{"key":"ref50","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: a review of programmed cell death","volume":"35","author":"S Elmore","year":"2007","journal-title":"Toxicol Pathol"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.1038\/labinvest.3700156","article-title":"Smad3 is required for dedifferentiation of retinal pigment epithelium following retinal detachment in mice","volume":"84","author":"S Saika","year":"2004","journal-title":"Lab Invest"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"647","DOI":"10.1001\/archopht.125.5.647","article-title":"Effect of Smad7 gene overexpression on transforming growth factor beta-induced retinal pigment fibrosis in a proliferative vitreoretinopathy mouse model","volume":"125","author":"S Saika","year":"2007","journal-title":"Arch Ophthalmol"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"8146","DOI":"10.1167\/iovs.12-10079","article-title":"Elucidation of the pathogenic mechanism of rhegmatogenous retinal detachment with proliferative vitreoretinopathy by proteomic analysis","volume":"53","author":"J Yu","year":"2012","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"3368","DOI":"10.1167\/iovs.10-6991","article-title":"Inhibition of Mdm2 sensitizes human retinal pigment epithelial cells to apoptosis","volume":"52","author":"S Bhattacharya","year":"2011","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref55","first-page":"3059","article-title":"Ischemic preconditioning attenuates apoptotic cell death in the rat retina","volume":"43","author":"C Zhang","year":"2002","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1167\/iovs.03-0805","article-title":"Effect of NF-kappa B inhibition on TNF-alpha-induced apoptosis in human RPE cells","volume":"45","author":"P Yang","year":"2004","journal-title":"Invest Ophthalmol Vis Sci"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1007\/s00296-009-1136-8","article-title":"Single-nucleotide polymorphisms p53 G72C and Mdm2 T309G in patients with psoriasis, psoriatic arthritis, and SAPHO syndrome","volume":"30","author":"G Assmann","year":"2010","journal-title":"Rheumatol Int"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"4205","DOI":"10.1158\/0008-5472.CAN-11-0058","article-title":"Targeting the p53 pathway in retinoblastoma with subconjunctival Nutlin-3a","volume":"71","author":"RC Brennan","year":"2011","journal-title":"Cancer Res"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1038\/ejhg.2008.106","article-title":"Gene-environment interactions for complex traits: definitions, methodological requirements and challenges","volume":"16","author":"A Dempfle","year":"2008","journal-title":"Eur J Hum Genet"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1146\/annurev.med.56.082103.104540","article-title":"Definition and clinical importance of haplotypes","volume":"56","author":"DC Crawford","year":"2005","journal-title":"Annu Rev Med"}],"container-title":["PLoS ONE"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pone.0082283","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,8,4]],"date-time":"2019-08-04T14:32:52Z","timestamp":1564929172000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0082283"}},"subtitle":[],"editor":[{"given":"Klaus","family":"Roemer","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2013,12,9]]},"references-count":60,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2013,12,9]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0082283","relation":{},"ISSN":["1932-6203"],"issn-type":[{"value":"1932-6203","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,12,9]]}}}