{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T15:19:23Z","timestamp":1790176763603,"version":"4.1.0"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T00:00:00Z","timestamp":1454544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Production of glycoconjugate vaccines involves the chemical conjugation of glycans to an immunogenic carrier protein such as Cross-Reactive-Material-197 (CRM\n                    <jats:sub>197<\/jats:sub>\n                    ). Instead of using glycans from natural sources recent vaccine development has been focusing on the use of synthetically defined minimal epitopes. While the glycan is structurally defined, the attachment sites on the protein are not. Fully characterized conjugates and batch-to-batch comparisons are the key to eventually create completely defined conjugates. A variety of glycoconjugates consisting of CRM\n                    <jats:sub>197<\/jats:sub>\n                    and synthetic oligosaccharide epitopes was characterised using mass spectrometry techniques. The primary structure was assessed by combining intact protein MALDI-TOF-MS, LC-MALDI-TOF-MS middle-down and LC-ESI-MS bottom-up approaches. The middle-down approach on CNBr cleaved glycopeptides provided almost complete sequence coverage, facilitating rapid batch-to-batch comparisons, resolving glycan loading and identification of side products. Regions close to the N- and C-termini were most efficiently conjugated.\n                  <\/jats:p>","DOI":"10.1038\/srep20488","type":"journal-article","created":{"date-parts":[[2016,2,4]],"date-time":"2016-02-04T06:35:01Z","timestamp":1454567701000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Cross Reactive Material 197 glycoconjugate vaccines contain privileged conjugation sites"],"prefix":"10.1038","volume":"6","author":[{"given":"Uwe","family":"M\u00f6ginger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anja","family":"Resemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Martin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharavathi","family":"Parameswarappa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subramanian","family":"Govindan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eike-Christian","family":"Wamhoff","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix","family":"Broecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Detlev","family":"Suckau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claney Lebev","family":"Pereira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chakkumkal","family":"Anish","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter H.","family":"Seeberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kolarich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2016,2,4]]},"reference":[{"key":"BFsrep20488_CR1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1007\/978-94-007-0940-9_13","volume":"715","author":"K Bazaka","year":"2011","unstructured":"Bazaka, K., Crawford, R. J., Nazarenko, E. L. & Ivanova, E. P. Bacterial Extracellular Polysaccharides. In: Bacterial Adhesion (eds Linke D., Goldman A. ). 715, 213\u2013226. Springer: Netherlands, (2011).","journal-title":"Bacterial Adhesion"},{"key":"BFsrep20488_CR2","doi-asserted-by":"crossref","first-page":"S49","DOI":"10.1093\/infdis\/165-Supplement_1-S49","volume":"165","author":"KE Stein","year":"1992","unstructured":"Stein, K. E. Thymus-independent and thymus-dependent responses to polysaccharide antigens. J of infec Dis 165 Suppl 1, S49\u201352 (1992).","journal-title":"J of infec Dis"},{"key":"BFsrep20488_CR3","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1084\/jem.50.4.533","volume":"50","author":"OT Avery","year":"1929","unstructured":"Avery, O. T. & Goebel, W. F. Chemo-immunological studies on conjugated carbohydrate-proteins: II. Immunological specificity of synthetic sugar-protein antigens. J Exp Med 50, 533 (1929).","journal-title":"J Exp Med"},{"key":"BFsrep20488_CR4","doi-asserted-by":"crossref","first-page":"730","DOI":"10.1542\/peds.60.5.730","volume":"60","author":"H Peltola","year":"1977","unstructured":"Peltola, H., Kayhty, H., Sivonen, A. & Makela, H. Haemophilus influenzae type b capsular polysaccharide vaccine in children: a double-blind field study of 100,000 vaccinees 3 months to 5 years of age in Finland. Pediatrics 60, 730\u2013737 (1977).","journal-title":"Pediatrics"},{"key":"BFsrep20488_CR5","unstructured":"Pon, R. A. Exploiting the Bacterial Surface: The Successfull Application of Glycoconjugate Vaccines In: Bacterial glycomics: current research, technology and applications (eds Reid C. W., Reid A. N., Twine S. M. ), 243\u2013262. Horizon Scientific Press (2012)."},{"key":"BFsrep20488_CR6","doi-asserted-by":"crossref","first-page":"4063","DOI":"10.1093\/nar\/12.10.4063","volume":"12","author":"G Giannini","year":"1984","unstructured":"Giannini, G., Rappuoli, R. & Ratti, G. The amino-acid sequence of two non-toxic mutants of diphtheria toxin: CRM45 and CRM197 . Nucleic Acids Res 12, 4063\u20134069 (1984).","journal-title":"Nucleic Acids Res"},{"key":"BFsrep20488_CR7","doi-asserted-by":"crossref","first-page":"4335","DOI":"10.1016\/j.vaccine.2010.04.072","volume":"28","author":"HR Shinefield","year":"2010","unstructured":"Shinefield, H. R. Overview of the development and current use of CRM197 conjugate vaccines for pediatric use. Vaccine 28, 4335\u20134339 (2010).","journal-title":"Vaccine"},{"key":"BFsrep20488_CR8","first-page":"1374","volume":"19","author":"SD Jin","year":"2009","unstructured":"Jin, S. D. et al. Optimization of capsular polysaccharide production by Streptococcus pneumoniae type 3. J Microbiol Biotechnol 19, 1374\u20131378 (2009).","journal-title":"J Microbiol Biotechnol"},{"key":"BFsrep20488_CR9","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1016\/j.carres.2012.11.017","volume":"366","author":"L Bertolo","year":"2013","unstructured":"Bertolo, L. et al. The design of a capsule polysaccharide conjugate vaccine against Campylobacter jejuni serotype HS15. Carbohydr Res 366, 45\u201349 (2013).","journal-title":"Carbohydr Res"},{"key":"BFsrep20488_CR10","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1002\/bip.20087","volume":"75","author":"NS Pujar","year":"2004","unstructured":"Pujar, N. S. et al. Base hydrolysis of phosphodiester bonds in pneumococcal polysaccharides. Biopolymers 75, 71\u201384 (2004).","journal-title":"Biopolymers"},{"key":"BFsrep20488_CR11","doi-asserted-by":"crossref","first-page":"6468","DOI":"10.1016\/j.vaccine.2009.06.013","volume":"27","author":"CE Frasch","year":"2009","unstructured":"Frasch, C. E. Preparation of bacterial polysaccharide-protein conjugates: analytical and manufacturing challenges. Vaccine 27, 6468\u20136470 (2009).","journal-title":"Vaccine"},{"key":"BFsrep20488_CR12","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1016\/j.chembiol.2014.01.002","volume":"21","author":"C Anish","year":"2014","unstructured":"Anish, C., Schumann, B., Pereira Claney, L. & Seeberger Peter, H. Chemical Biology Approaches to Designing Defined Carbohydrate Vaccines. Chem Biol 21, 38\u201350 (2014).","journal-title":"Chem Biol"},{"key":"BFsrep20488_CR13","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1126\/science.1095209","volume":"305","author":"V Verez-Bencomo","year":"2004","unstructured":"Verez-Bencomo, V. A Synthetic Conjugate Polysaccharide Vaccine Against Haemophilus influenzae Type b. Science 305, 522\u2013525 (2004).","journal-title":"Science"},{"key":"BFsrep20488_CR14","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/nature05819","volume":"446","author":"PH Seeberger","year":"2007","unstructured":"Seeberger, P. H. & Werz, D. B. Synthesis and medical applications of oligosaccharides. Nature 446, 1046\u20131051 (2007).","journal-title":"Nature"},{"key":"BFsrep20488_CR15","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1517\/17460441.2011.609554","volume":"6","author":"P Costantino","year":"2011","unstructured":"Costantino, P., Rappuoli, R. & Berti, F. The design of semi-synthetic and synthetic glycoconjugate vaccines. Expert Opin Drug Discov 6, 1045\u20131066 (2011).","journal-title":"Expert Opin Drug Discov"},{"key":"BFsrep20488_CR16","doi-asserted-by":"crossref","first-page":"4450","DOI":"10.1128\/iai.59.12.4450-4458.1991","volume":"59","author":"CY Chu","year":"1991","unstructured":"Chu, C. Y. et al. Preparation, characterization and immunogenicity of conjugates composed of the O-specific polysaccharide of Shigella dysenteriae type 1 (Shiga's bacillus) bound to tetanus toxoid. Infect Immun 59, 4450\u20134458 (1991).","journal-title":"Infect Immun"},{"key":"BFsrep20488_CR17","doi-asserted-by":"crossref","first-page":"5574","DOI":"10.1016\/j.vaccine.2009.07.036","volume":"27","author":"M Broker","year":"2009","unstructured":"Broker, M., Dull, P. M., Rappuoli, R. & Costantino, P. Chemistry of a new investigational quadrivalent meningococcal conjugate vaccine that is immunogenic at all ages. Vaccine 27, 5574\u20135580 (2009).","journal-title":"Vaccine"},{"key":"BFsrep20488_CR18","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/0022-1759(89)90298-6","volume":"120","author":"JM Peeters","year":"1989","unstructured":"Peeters, J. M., Hazendonk, T. G., Beuvery, E. C. & Tesser, G. I. Comparison of four bifunctional reagents for coupling peptides to proteins and the effect of the three moieties on the immunogenicity of the conjugates. J Immunol Methods 120, 133\u2013143 (1989).","journal-title":"J Immunol Methods"},{"key":"BFsrep20488_CR19","doi-asserted-by":"crossref","first-page":"3517","DOI":"10.1002\/chem.200400074","volume":"10","author":"T Buskas","year":"2004","unstructured":"Buskas, T., Li, Y. & Boons, G. J. The immunogenicity of the tumor-associated antigen Lewis(y) may be suppressed by a bifunctional cross-linker required for coupling to a carrier protein. Chemistry 10, 3517\u20133524 (2004).","journal-title":"Chemistry"},{"key":"BFsrep20488_CR20","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1002\/cbic.201300785","volume":"15","author":"S Crotti","year":"2014","unstructured":"Crotti, S. et al. Defined conjugation of glycans to the lysines of CRM197 guided by their reactivity mapping. ChemBioChem 15, 836\u2013843 (2014).","journal-title":"ChemBioChem"},{"key":"BFsrep20488_CR21","doi-asserted-by":"crossref","first-page":"1686","DOI":"10.1002\/cbic.201000235","volume":"11","author":"Q Li","year":"2010","unstructured":"Li, Q., Rodriguez, L. G., Farnsworth, D. F. & Gildersleeve, J. C. Effects of hapten density on the induced antibody repertoire. ChemBioChem 11, 1686\u20131691 (2010).","journal-title":"ChemBioChem"},{"key":"BFsrep20488_CR22","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1002\/eji.1830050807","volume":"5","author":"C Desaymard","year":"1975","unstructured":"Desaymard, C. & Howard, J. G. Role of epitope density in the induction of immunity and tolerance with thymus-independent antigens. II. Studies with 2,4-dinitrophenyl conjugates in vivo. Eur J of Immunol 5, 541\u2013545 (1975).","journal-title":"Eur J of Immunol"},{"key":"BFsrep20488_CR23","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1021\/bk-2008-0989.ch002","volume":"989","author":"C Jones","year":"2008","unstructured":"Jones, C. The Regulatory Framework for Glycoconjugate Vaccines. In: Carbohydrate-Based Vaccines (eds Roy, R. ). 989, 21\u201335. American Chemical Society (2008).","journal-title":"Carbohydrate-Based Vaccines"},{"key":"BFsrep20488_CR24","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1590\/S0001-37652005000200009","volume":"77","author":"C Jones","year":"2005","unstructured":"Jones, C. Vaccines based on the cell surface carbohydrates of pathogenic bacteria. An Acad Bras Cienc 77, 293\u2013324 (2005).","journal-title":"An Acad Bras Cienc"},{"key":"BFsrep20488_CR25","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/1045-1056(91)90023-D","volume":"19","author":"C Jones","year":"1991","unstructured":"Jones, C. & Currie, F. Control of components of bacterial polysaccharide vaccines by physical methods. Biologicals 19, 41\u201347 (1991).","journal-title":"Biologicals"},{"key":"BFsrep20488_CR26","doi-asserted-by":"crossref","first-page":"1128","DOI":"10.1128\/IAI.01056-08","volume":"77","author":"MA Monteiro","year":"2009","unstructured":"Monteiro, M. A. et al. Capsule polysaccharide conjugate vaccine against diarrheal disease caused by Campylobacter jejuni. Infect Immun 77, 1128\u20131136 (2009).","journal-title":"Infect Immun"},{"key":"BFsrep20488_CR27","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S0075-7535(08)70242-0","volume":"9","author":"G Allen","year":"1981","unstructured":"Allen, G. Chapter 3 Specific cleavage of the protein. In: Laboratory Techniques in Biochemistry and Molecular Biology (eds Allen G. ). 9, 43\u201371. Elsevier (1981).","journal-title":"Laboratory Techniques in Biochemistry and Molecular Biology"},{"key":"BFsrep20488_CR28","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1038\/nprot.2012.062","volume":"7","author":"D Kolarich","year":"2012","unstructured":"Kolarich, D., Jensen, P. H., Altmann, F. & Packer, N. H. Determination of site-specific glycan heterogeneity on glycoproteins. Nat Protoc 7, 1285\u20131298 (2012).","journal-title":"Nat Protoc"},{"key":"BFsrep20488_CR29","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jchromb.2006.09.041","volume":"849","author":"M Wuhrer","year":"2007","unstructured":"Wuhrer, M., Catalina, M. I., Deelder, A. M. & Hokke, C. H. Glycoproteomics based on tandem mass spectrometry of glycopeptides. J Chromatogr B Analyt Technol Biomed Life Sci 849, 115\u2013128 (2007).","journal-title":"J Chromatogr B Analyt Technol Biomed Life Sci"},{"key":"BFsrep20488_CR30","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1002\/rcm.3850","volume":"23","author":"WR Alley Jr.","year":"2009","unstructured":"Alley, W. R., Jr., Mechref, Y. & Novotny, M. V. Characterization of glycopeptides by combining collision-induced dissociation and electron-transfer dissociation mass spectrometry data. Rapid Commun Mass Spectrom : RCM 23, 161\u2013170 (2009).","journal-title":"Rapid Commun Mass Spectrom : RCM"},{"key":"BFsrep20488_CR31","doi-asserted-by":"crossref","unstructured":"Leymarie, N. et al. Interlaboratory Study on Differential Analysis of Protein Glycosylation by Mass Spectrometry: the ABRF Glycoprotein Research Multi-Institutional Study 2012. Mol Cell Proteomics, (2013).","DOI":"10.1074\/mcp.M113.030643"},{"key":"BFsrep20488_CR32","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1002\/jms.3210","volume":"48","author":"K Stavenhagen","year":"2013","unstructured":"Stavenhagen, K. et al. Quantitative mapping of glycoprotein micro-heterogeneity and macro-heterogeneity: an evaluation of mass spectrometry signal strengths using synthetic peptides and glycopeptides. J Mass Spectrom : JMS 48, 627\u2013639 (2013).","journal-title":"J Mass Spectrom : JMS"},{"key":"BFsrep20488_CR33","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1021\/ja01467a052","volume":"83","author":"E Gross","year":"1961","unstructured":"Gross, E. & Witkop, B. Selective Cleavage of the Methionyl Peptide Bonds in Ribonuclease with Cyanogen Bromide1. J Am Chem Soc 83, 1510\u20131511 (1961).","journal-title":"J Am Chem Soc"},{"key":"BFsrep20488_CR34","doi-asserted-by":"crossref","first-page":"4407","DOI":"10.1021\/ol048614m","volume":"6","author":"X Wu","year":"2004","unstructured":"Wu, X., Ling, C. C. & Bundle, D. R. A new homobifunctional p-nitro phenyl ester coupling reagent for the preparation of neoglycoproteins. Org Lett 6, 4407\u20134410 (2004).","journal-title":"Org Lett"},{"key":"BFsrep20488_CR35","first-page":"258","volume":"20","author":"D Suckau","year":"2009","unstructured":"Suckau, D. & Resemann, A. MALDI top-down sequencing: calling N-and C-terminal protein sequences with high confidence and speed. J Biomol Tech 20, 258 (2009).","journal-title":"J Biomol Tech"},{"key":"BFsrep20488_CR36","doi-asserted-by":"crossref","first-page":"672","DOI":"10.1002\/mas.20142","volume":"26","author":"J Hardouin","year":"2007","unstructured":"Hardouin, J. Protein sequence information by matrix-assisted laser desorption\/ionization in-source decay mass spectrometry. Mass Spectrom Rev 26, 672\u2013682 (2007).","journal-title":"Mass Spectrom Rev"},{"key":"BFsrep20488_CR37","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1021\/ac034362b","volume":"75","author":"D Suckau","year":"2003","unstructured":"Suckau, D. & Resemann, A. T3-sequencing: targeted characterization of the N-and C-termini of undigested proteins by mass spectrometry. Anal Chem 75, 5817\u20135824 (2003).","journal-title":"Anal Chem"},{"key":"BFsrep20488_CR38","doi-asserted-by":"crossref","first-page":"3283","DOI":"10.1021\/ac1000515","volume":"82","author":"A Resemann","year":"2010","unstructured":"Resemann, A. et al. Top-Down de Novo Protein Sequencing of a 13.6 kDa Camelid Single Heavy Chain Antibody by Matrix-Assisted Laser Desorption Ionization-Time-of-Flight\/Time-of-Flight Mass Spectrometry. Anal Chem 82, 3283\u20133292 (2010).","journal-title":"Anal Chem"},{"key":"BFsrep20488_CR39","doi-asserted-by":"crossref","first-page":"5229","DOI":"10.1073\/pnas.1201964109","volume":"109","author":"E Malito","year":"2012","unstructured":"Malito, E. et al. Structural basis for lack of toxicity of the diphtheria toxin mutant CRM197 . Proc Natl Acad Sci USA 109, 5229\u20135234 (2012).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep20488_CR40","doi-asserted-by":"crossref","first-page":"8898","DOI":"10.1073\/pnas.84.24.8898","volume":"84","author":"S Marqusee","year":"1987","unstructured":"Marqusee, S. & Baldwin, R. L. Helix stabilization by Glu-...Lys+ salt bridges in short peptides of de novo design. Proc Natl Acad Sci USA 84, 8898\u20138902 (1987).","journal-title":"Proc Natl Acad Sci USA"},{"key":"BFsrep20488_CR41","doi-asserted-by":"crossref","first-page":"887","DOI":"10.1038\/nbt1329","volume":"25","author":"CF Taylor","year":"2007","unstructured":"Taylor, C. F. et al. The minimum information about a proteomics experiment (MIAPE). Nat Biotechnol 25, 887\u2013893 (2007).","journal-title":"Nat Biotechnol"},{"key":"BFsrep20488_CR42","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1074\/mcp.O112.026492","volume":"12","author":"D Kolarich","year":"2013","unstructured":"Kolarich, D. et al. The minimum information required for a glycomics experiment (MIRAGE) project: improving the standards for reporting mass-spectrometry-based glycoanalytic data. Mol Cell Proteomics 12, 991\u2013995 (2013).","journal-title":"Mol Cell Proteomics"},{"key":"BFsrep20488_CR43","doi-asserted-by":"crossref","first-page":"10260","DOI":"10.1039\/c1cc13614c","volume":"47","author":"CE Martin","year":"2011","unstructured":"Martin, C. E., Weishaupt, M. W. & Seeberger, P. H. Progress toward developing a carbohydrate-conjugate vaccine against Clostridium difficile ribotype 027: synthesis of the cell-surface polysaccharide PS-I repeating unit. Chem Commun (Camb) 47, 10260\u201310262 (2011).","journal-title":"Chem Commun (Camb)"},{"key":"BFsrep20488_CR44","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1002\/1521-3765(20011015)7:20<4411::AID-CHEM4411>3.0.CO;2-T","volume":"7","author":"DJ Lefeber","year":"2001","unstructured":"Lefeber, D. J., Kamerling, J. P. & Vliegenthart, J. F. Synthesis of Streptococcus pneumoniae type 3 neoglycoproteins varying in oligosaccharide chain length, loading and carrier protein. Chemistry 7, 4411\u20134421 (2001).","journal-title":"Chemistry"},{"key":"BFsrep20488_CR45","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1021\/cb600086b","volume":"1","author":"X Liu","year":"2006","unstructured":"Liu, X. et al. Enhancement of the immunogenicity of synthetic carbohydrates by conjugation to virosomes: a leishmaniasis vaccine candidate. ACS Chem Biol 1, 161\u2013164 (2006).","journal-title":"ACS Chem Biol"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep20488.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20488","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep20488.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T21:53:44Z","timestamp":1672869224000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep20488"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,4]]},"references-count":45,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,22]]}},"alternative-id":["BFsrep20488"],"URL":"https:\/\/doi.org\/10.1038\/srep20488","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,4]]},"assertion":[{"value":"12 August 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A.R and D.S. are employees of Bruker,Bremen.The other authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"20488"}}