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ascites tumor cells [Journal Article]","volume":"63","author":"JS Olavarria","year":"1981","journal-title":"Biochimie"},{"issue":"2","key":"ref74","first-page":"339","article-title":"Glutamine and glucose as energy substrates for Ehrlich ascites tumour cells [Journal Article]","volume":"16","author":"MA Medina","year":"1988","journal-title":"Biochem Int"},{"issue":"1","key":"ref75","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-4652(199701)170:1<1::AID-JCP1>3.0.CO;2-S","article-title":"Method for measuring a comprehensive energy budget in a proliferating cell system over multiple cell cycles [Journal Article]","volume":"170","author":"M Guppy","year":"1997","journal-title":"J Cell Physiol"},{"key":"ref76","unstructured":"Beucher S, Lantu\u00e9joul, C. Use of watersheds in contour detection. 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