{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,24]],"date-time":"2025-10-24T08:07:23Z","timestamp":1761293243525},"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"2","license":[{"start":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T00:00:00Z","timestamp":1424995200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1004062","type":"journal-article","created":{"date-parts":[[2015,2,27]],"date-time":"2015-02-27T18:53:16Z","timestamp":1425063196000},"page":"e1004062","update-policy":"http:\/\/dx.doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":18,"title":["Cyclin and DNA Distributed Cell Cycle Model for GS-NS0 Cells"],"prefix":"10.1371","volume":"11","author":[{"given":"David G.","family":"Garc\u00eda M\u00fcnzer","sequence":"first","affiliation":[]},{"given":"Margaritis","family":"Kostoglou","sequence":"additional","affiliation":[]},{"given":"Michael C.","family":"Georgiadis","sequence":"additional","affiliation":[]},{"given":"Efstratios N.","family":"Pistikopoulos","sequence":"additional","affiliation":[]},{"given":"Athanasios","family":"Mantalaris","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2015,2,27]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1038\/nrd3229","article-title":"Development trends for human monoclonal antibody therapeutics","volume":"9","author":"AL Nelson","year":"2010","journal-title":"Nat Rev Drug Discov"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1002\/bit.22946","article-title":"Selection of CHO host cell subclones with increased specific antibody production rates by repeated cycles of transient transfection and cell sorting","volume":"108","author":"J Pichler","year":"2011","journal-title":"Biotechnology and Bioengineering"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"419","DOI":"10.1007\/s12257-012-0577-1","article-title":"Analysis of heterogeneity and instability of stable mAb-expressing CHO cells","volume":"18","author":"ZM Du","year":"2013","journal-title":"Biotechnology and Bioprocess Engineering"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1002\/bit.24621","article-title":"Functional heterogeneity and heritability in CHO cell populations","volume":"110","author":"SL Davies","year":"2013","journal-title":"Biotechnology and Bioengineering"},{"key":"ref5","article-title":"Phenotypical Genomics of Bacteria Escherichia Coli","author":"Z Zhang","year":"2007"},{"key":"ref6","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0008432","article-title":"Intraclonal protein expression heterogeneity in recombinant CHO cells","volume":"4","author":"W Pilbrough","year":"2009","journal-title":"PLoS One"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"7990","DOI":"10.1021\/ie100125a","article-title":"Multi-scale modeling of heterogeneities in mammalian cell culture processes","volume":"49","author":"S Karra","year":"2010","journal-title":"Industrial & Engineering Chemistry Research"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/0168-1656(90)90066-K","article-title":"Mechanisms and kinetics of monoclonal-antibody synthesis and secretion in synchronous and asynchronous hybridoma cell-cultures","volume":"16","author":"M Alrubeai","year":"1990","journal-title":"Journal of Biotechnology"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1007\/BF02521735","article-title":"Specific monoclonal-antibody productivity and the cell cycle-comparisons of batch, continuous and perfusion cultures","volume":"9","author":"M Alrubeai","year":"1992","journal-title":"Cytotechnology"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10616-006-9041-4","article-title":"Cell cycle phase dependent productivity of a recombinant Chinese hamster ovary cell line","volume":"52","author":"RL Dutton","year":"2006","journal-title":"Cytotechnology"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1007\/s00449-008-0236-2","article-title":"Metabolic flux-based modeling of mAb production during batch and fed-batch operations","volume":"32","author":"P Dorka","year":"2009","journal-title":"Bioprocess Biosyst Eng"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ymben.2010.09.003","article-title":"Dynamic model of CHO cell metabolism","volume":"13","author":"RP Nolan","year":"2011","journal-title":"Metab Eng"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"3025","DOI":"10.1002\/bit.23269","article-title":"Metabolite profiling of recombinant CHO cells: designing tailored feeding regimes that enhance recombinant antibody production","volume":"108","author":"CA Sellick","year":"2011","journal-title":"Biotechnology and Bioengineering"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1002\/bit.24858","article-title":"Peak antibody production is associated with increased oxidative metabolism in an industrially relevant fed-batch CHO cell culture","volume":"110","author":"N Templeton","year":"2013","journal-title":"Biotechnology and Bioengineering"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.tibtech.2010.03.002","article-title":"Single cell analysis: the new frontier in \u2018omics\u2019","volume":"28","author":"D Wang","year":"2010","journal-title":"Trends in Biotechnology"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.jbiotec.2008.03.019","article-title":"Mammalian cell culture scale-up and fed-batch control using automated flow cytometry","volume":"135","author":"G Sitton","year":"2008","journal-title":"Journal of Biotechnology"},{"key":"ref17","first-page":"109","article-title":"Metabolic flux analysis in systems biology of mammalian cells","author":"J Niklas","year":"2012"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1007\/s004490100265","article-title":"Metabolic engineering of animal cells","volume":"24","author":"F G\u00f2dia","year":"2002","journal-title":"Bioprocess Biosyst Eng"},{"key":"ref19","doi-asserted-by":"crossref","DOI":"10.1016\/S0065-2164(08)70413-1","article-title":"Mathematical models in fermentation processes","volume":"23","author":"AG Fredrickson","year":"1970","journal-title":"Advanced Applied Microbiology"},{"key":"ref20","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1007\/BF00749616","article-title":"MODELING OF CELL-CULTURE PROCESSES","volume":"14","author":"E Tziampazis","year":"1994","journal-title":"Cytotechnology"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"1242","DOI":"10.1016\/j.compchemeng.2006.10.016","article-title":"A feasible solution technique for higher-dimensional population balance models","volume":"31","author":"MA Pinto","year":"2007","journal-title":"Computers & Chemical Engineering"},{"key":"ref22","first-page":"403","article-title":"Model development and analysis of mammalian cell culture systems","author":"A Kiparissides","year":"2010"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1002\/bit.260260810","article-title":"A finite representation model for an asynchronous culture of Escherichia-coli","volume":"26","author":"MM Domach","year":"1984","journal-title":"Biotechnology and Bioengineering"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.compchemeng.2004.08.018","article-title":"Cell ensemble modeling of metabolic oscillations in continuous yeast cultures","volume":"29","author":"MA Henson","year":"2005","journal-title":"Computers & Chemical Engineering"},{"key":"ref25","article-title":"Theory and Applications to Particulate Systems in Engineering","author":"D Ramkrishna","year":"2000"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"1411","DOI":"10.1016\/S0098-1354(01)00709-8","article-title":"Numerical solution of multi-variable cell population balance models: I. Finite difference methods","volume":"25","author":"NV Mantzaris","year":"2001","journal-title":"Computers & Chemical Engineering"},{"key":"ref27","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/S0098-1354(01)00710-4","article-title":"Numerical solution of multi-variable cell population balance models. II. Spectral methods","volume":"25","author":"NV Mantzaris","year":"2001","journal-title":"Computers & Chemical Engineering"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/S0098-1354(01)00711-6","article-title":"Numerical solution of multi-variable cell population balance models. III. Finite element methods","volume":"25","author":"NV Mantzaris","year":"2001","journal-title":"Computers & Chemical Engineering"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0009-2509(01)00356-6","article-title":"Nonlinear productivity control using a multi-staged cell population balance model","volume":"57","author":"NV Mantzaris","year":"2002","journal-title":"Chemical Engineering Science"},{"key":"ref30","doi-asserted-by":"crossref","first-page":"5801","DOI":"10.1021\/ie0511581","article-title":"A coupled single cell-population-balance model for mammalian cell cultures","volume":"45","author":"FR Sidoli","year":"2006","journal-title":"Industrial & Engineering Chemistry Research"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"1322","DOI":"10.1002\/bit.260421109","article-title":"Growth and production modeling in hybridoma continuous cultures","volume":"42","author":"L Cazzador","year":"1993","journal-title":"Biotechnology and Bioengineering"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0303-2647(95)01524-O","article-title":"Multistaged corpuscular models of microbial\u2014growth\u2014Monte\u2014Carlo Simulations","volume":"36","author":"C Hatzis","year":"1995","journal-title":"Biosystems"},{"key":"ref33","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1002\/bit.260480109","article-title":"A combined cell-cycle and metabolic model for the growth of hybridoma cells in steady-state continuous-culture","volume":"48","author":"DE Martens","year":"1995","journal-title":"Biotechnology and Bioengineering"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1002\/(SICI)1097-0290(19980520)58:4<387::AID-BIT6>3.0.CO;2-F","article-title":"Transition probability cell cycle model with product formation","volume":"58","author":"SJ Cain","year":"1998","journal-title":"Biotechnology and Bioengineering"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1007\/BF02345138","article-title":"Three-dimensional cell cycle model with distributed transcription and translation","volume":"43","author":"KJ Rounseville","year":"2005","journal-title":"Med Biol Eng Comput"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1016\/S0168-1656(99)00020-6","article-title":"Numerical solution of a mass structured cell population balance model in an environment of changing substrate concentration","volume":"71","author":"NV Mantzaris","year":"1999","journal-title":"Journal of Biotechnology"},{"key":"ref37","first-page":"1198","article-title":"A population balance model describing the cell cycle dynamics of myeloma cell cultivation","volume":"23","author":"YH Liu","year":"2007","journal-title":"Biotechnology Progress"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"918","DOI":"10.1038\/ncb1001-918","article-title":"Extracellular control of cell size","volume":"3","author":"IJ Conlon","year":"2001","journal-title":"Nature cell biology"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1475-4924-2-7","article-title":"Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression","volume":"2","author":"I Conlon","year":"2003","journal-title":"Journal of biology"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"218","DOI":"10.4161\/cc.6.2.3744","article-title":"Cell size regulation in mammalian cells","volume":"6","author":"P Echave","year":"2007","journal-title":"Cell Cycle"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1126\/science.2683075","article-title":"G1 events and regulation of cell-proliferation","volume":"246","author":"AB Pardee","year":"1989","journal-title":"Science"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"872","DOI":"10.1016\/0955-0674(94)90059-0","article-title":"Cell cycle checkpoints","volume":"6","author":"A Murray","year":"1994","journal-title":"Current Opinion in Cell Biology"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/(SICI)1097-0320(19960901)25:1<1::AID-CYTO1>3.0.CO;2-N","article-title":"Cytometry of cyclin proteins","volume":"25","author":"Z Darzynkiewicz","year":"1996","journal-title":"Cytometry"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1038\/374131a0","article-title":"Principles of CDK regulation","volume":"374","author":"DO Morgan","year":"1995","journal-title":"Nature"},{"key":"ref45","article-title":"Development of a combined mathematical and experimental framework model for modeling mammalian cell cultures","author":"C Kontoravdi","year":"2006"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1023\/B:CYTO.0000043397.94527.84","article-title":"Modelling of mammalian cells and cell culture processes","volume":"44","author":"FR Sidoli","year":"2004","journal-title":"Cytotechnology"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1016\/j.automatica.2011.01.013","article-title":"\u2032Closing the loop\u2032 in biological systems modeling\u2014From the in silico to the in vitro","volume":"47","author":"A Kiparissides","year":"2011","journal-title":"Automatica"},{"key":"ref48","first-page":"137","article-title":"Modeling Frameworks of Complex Separation Systems","author":"MC Georgiadis","year":"2008"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1016\/j.bej.2013.10.008","article-title":"Developing a cyclin blueprint as a tool for mapping the cell cycle in GS-NSO","volume":"81","author":"DGG Munzer","year":"2013","journal-title":"Biochemical Engineering Journal"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1023\/A:1008170710003","article-title":"Advances in animal cell recombinant protein production: GS-NS0 expression system","volume":"32","author":"LM Barnes","year":"2000","journal-title":"Cytotechnology"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1002\/btpr.647","article-title":"Development of a mathematical model for evaluating the dynamics of normal and apoptotic Chinese hamster ovary cells","volume":"27","author":"S Naderi","year":"2011","journal-title":"Biotechnology Progress"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1042\/BA20060021","article-title":"A macrokinetic model for myeloma cell culture based on stoichiometric balance","volume":"46","author":"F Zhou","year":"2007","journal-title":"Biotechnology and Applied Biochemistry"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1007\/s12257-008-0223-0","article-title":"Responses of GS-NS0 myeloma cells to osmolality: cell growth, intracellular mass metabolism, energy metabolism, and antibody production","volume":"14","author":"L Zhao","year":"2009","journal-title":"Biotechnology and Bioprocess Engineering"},{"key":"ref54","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/bit.260390408","article-title":"Effects of ammonia and lactate on hybridoma growth, metabolism, and antibody production","volume":"39","author":"SS Ozturk","year":"1992","journal-title":"Biotechnology and Bioengineering"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/j.ymben.2011.12.006","article-title":"On metabolic shift to lactate consumption in fed-batch culture of mammalian cells","volume":"14","author":"BC Mulukutla","year":"2012","journal-title":"Metab Eng"},{"key":"ref56","doi-asserted-by":"crossref","DOI":"10.1002\/9780470757086","article-title":"Principles of cell proliferation","author":"JK Heath","year":"2001"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1016\/j.matcom.2012.03.005","article-title":"Synchronisation and control of proliferation in cycling cell population models with age structure","volume":"96","author":"F Billy","year":"2014","journal-title":"Mathematics and Computers in Simulation"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1021\/bp050028k","article-title":"Application of global sensitivity analysis to determine goals for design of experiments: An example study on antibody-producing cell cultures","volume":"21","author":"C Kontoravdi","year":"2005","journal-title":"Biotechnology Progress"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/S1570-7946(10)28099-9","article-title":"Towards energy-based dynamic optimization of monoclonal antibody producing GS-NS0 cultures","volume":"28","author":"A Kiparissides","year":"2010","journal-title":"20th European Symposium on Computer Aided Process Engineering"},{"key":"ref60","first-page":"98","article-title":"Applications of mathematics to medical problems","volume":"54","author":"AG McKendrick","year":"1926","journal-title":"Proceedings of the Edinburgh Mathematical Society"},{"key":"ref61","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1080\/00986449508936360","article-title":"Evaluation of numerical methods for simulating an evolving particle size distribution in growth processes","volume":"136","author":"A Kostoglou","year":"1995","journal-title":"Chem Eng Commun"},{"key":"ref62","article-title":"Numerical Solution of Partial Differential Equations in Science and Engineering","author":"L Lapidus","year":"1982"},{"key":"ref63","first-page":"247","article-title":"Development of a combined mathematical and experimental framework for the control and optimisation of mammalian cell culture systems","author":"A Kiparissides","year":"2012"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.envsoft.2008.12.002","article-title":"GUI\u2014HDMR\u2014A software tool for global sensitivity analysis of complex models","volume":"24","author":"T Ziehn","year":"2009","journal-title":"Environmental Modelling & Software"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1021\/ie0401556","article-title":"Toward global parametric estimability of a large-scale kinetic single-cell model for mammalian cell cultures","volume":"44","author":"FR Sidoli","year":"2005","journal-title":"Industrial & Engineering Chemistry Research"},{"key":"ref66","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/sj.onc.1202040","article-title":"Early G(1) growth arrest of hybridoma B cells by DMSO involves cyclin D2 inhibition and p21(CIP1) induction","volume":"17","author":"G Ponzio","year":"1998","journal-title":"Oncogene"},{"key":"ref67","doi-asserted-by":"crossref","first-page":"7168","DOI":"10.1021\/ie900139x","article-title":"Global sensitivity analysis challenges in biological systems modeling","volume":"48","author":"A Kiparissides","year":"2009","journal-title":"Industrial & Engineering Chemistry Research"},{"key":"ref68","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1023\/A:1007940119503","article-title":"Descriptive parameter evaluation in mammalian cell culture","volume":"26","author":"RL Dutton","year":"1998","journal-title":"Cytotechnology"},{"key":"ref69","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1021\/bp9701269","article-title":"Mathematical modeling and analysis in biochemical engineering: Past accomplishments and future opportunities","volume":"14","author":"JE Bailey","year":"1998","journal-title":"Biotechnology Progress"},{"key":"ref70","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1016\/0092-8674(92)90360-O","article-title":"Identification And Properties Of An Atypical Catalytic Subunit (P34(PSK-J3)\/CDK4) For Mammalian-D Type-G1 Cyclins","volume":"71","author":"H Matsushime","year":"1992","journal-title":"Cell"},{"key":"ref71","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1016\/0092-8674(93)90636-5","article-title":"Mammalian G(1)-cyclins","volume":"73","author":"CJ Sherr","year":"1993","journal-title":"Cell"},{"key":"ref72","article-title":"Molecular Biology of The Cell","author":"B Alberts","year":"2008"},{"key":"ref73","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/S0037-1963(01)90051-4","article-title":"Flow cytometry in analysis of cell cycle and apoptosis","volume":"38","author":"Z Darzynkiewicz","year":"2001","journal-title":"Seminars in Hematology"},{"key":"ref74","doi-asserted-by":"crossref","first-page":"1735","DOI":"10.1002\/bit.24826","article-title":"Metabolic analysis of antibody producing CHO cells in fed-batch production","volume":"110","author":"J Dean","year":"2013","journal-title":"Biotechnology and Bioengineering"},{"key":"ref75","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/(SICI)1097-0290(19970905)55:5<783::AID-BIT8>3.0.CO;2-7","article-title":"Fed-batch culture of recombinant NS0 myeloma cells with high monoclonal antibody production","volume":"55","author":"WC Zhou","year":"1997","journal-title":"Biotechnology and Bioengineering"},{"key":"ref76","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1016\/j.jbiotec.2012.08.021","article-title":"Multivariate analysis of cell culture bioprocess data--lactate consumption as process indicator","volume":"162","author":"H Le","year":"2012","journal-title":"Journal of Biotechnology"},{"key":"ref77","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1007\/s10616-007-9047-6","article-title":"Proliferation control strategies to improve productivity and survival during CHO based production culture\u2014A summary of recent methods employed and the effects of proliferation control in product secreting CHO cell lines","volume":"53","author":"N Kumar","year":"2007","journal-title":"Cytotechnology"},{"key":"ref78","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1002\/bit.21263","article-title":"Dynamic analysis of GS-NS0 cells producing a recombinant monoclonal antibody during fed-batch culture","volume":"97","author":"SH Stansfield","year":"2007","journal-title":"Biotechnology and Bioengineering"},{"key":"ref79","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.jbiosc.2011.08.022","article-title":"Computational approach for understanding and improving GS-NS0 antibody production under hyperosmotic conditions","volume":"113","author":"Y Ho","year":"2012","journal-title":"Journal of Bioscience and Bioengineering"},{"key":"ref80","doi-asserted-by":"crossref","first-page":"1730","DOI":"10.1002\/btpr.688","article-title":"A dynamic mathematical model for monoclonal antibody N-linked glycosylation and nucleotide sugar donor transport within a maturing Golgi apparatus","volume":"27","author":"I Jimenez del Val","year":"2011","journal-title":"Biotechnology Progress"},{"key":"ref81","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1038\/nbt0693-720","article-title":"Culture pH affects expression rates and glycosylation of recombinant mouse placental lactogen proteins by Chinese hamster ovary (CHO) cells","volume":"11","author":"MC Borys","year":"1993","journal-title":"Bio\/technology (Nature Publishing Company)"},{"key":"ref82","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1002\/1097-0290(20001005)70:1<25::AID-BIT4>3.0.CO;2-Q","article-title":"Multiple cell culture factors can affect the glycosylation of Asn-184 in CHO-produced tissue-type plasminogen activator","volume":"70","author":"DC Andersen","year":"2000","journal-title":"Biotechnology and Bioengineering"},{"key":"ref83","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1002\/bit.21013","article-title":"Process parameter shifting: Part I. Effect of DOT, pH, and temperature on the performance of Epo-Fc expressing CHO cells cultivated in controlled batch bioreactors","volume":"94","author":"E Trummer","year":"2006","journal-title":"Biotechnology and Bioengineering"},{"key":"ref84","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1002\/bit.22348","article-title":"Identification of cell culture conditions to control N-glycosylation site-occupancy of recombinant glycoproteins expressed in CHO cells","volume":"103","author":"M Gawlitzek","year":"2009","journal-title":"Biotechnology and Bioengineering"},{"key":"ref85","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1002\/1097-0290(20010320)72:6<592::AID-BIT1024>3.0.CO;2-J","article-title":"Comparative analysis of two controlled proliferation strategies regarding product quality, influence on tetracycline-regulated gene expression, and productivity","volume":"72","author":"H Kaufmann","year":"2001","journal-title":"Biotechnology and Bioengineering"}],"container-title":["PLOS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004062","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2018,10,19]],"date-time":"2018-10-19T19:11:55Z","timestamp":1539976315000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1004062"}},"subtitle":[],"editor":[{"given":"Daniel A","family":"Beard","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2015,2,27]]},"references-count":85,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2015,2,27]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1004062","relation":{},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,2,27]]}}}