Publications BPE group

2021

Journal Article

Bartholomäus, A.; Kolte, B.; Mustafayeva, A.; Goebel, I.; Fuchs, S.; Benndorf, D.; Engelmann, S.; Ignatova, Z.: smORFer: a modular algorithm to detect small ORFs in prokaryotes. Nucleic Acids Research (London) 49 (15), e89 (2021)

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Bastida, F.; Jehmlich, N.; Starke, R.; Schallert, K.; Benndorf, D.; López-Mondéjar, R.; Plaza, C.; Freixino, Z.; Ramírez-Ortuño, C.; Ruiz-Navarro, A. et al.; Díaz-López, M.; Vera, A.; Moreno, J.L.; Eldridge, D.J.; García, C.; Delgado-Baquerizo, M.: Structure and function of bacterial metaproteomes across biomes. Soil Biology and Biochemistry 160, 108331 (2021)

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Biemann, R.; Buß, E.; Benndorf, D.; Lehmann, T.; Schallert, K.; Püttker, S.; Reichl, U.; Isermann, B.; Schneider, J. G.; Saake, G. et al.; Heyer, R.: Fecal Metaproteomics Reveals Reduced Gut Inflammation and Changed Microbial Metabolism Following Lifestyle-Induced Weight Loss. Biomolecules 11 (5), 726 (2021)

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Bissinger, T.; Wu, Y.; Marichal-Gallardo, P.; Riedel, D.; Liu, X.; Genzel, Y.; Tan, W.; Reichl, U.: Towards integrated production of an influenza A vaccine candidate with MDCK suspension cells. Biotechnology and Bioengineering 118 (10), pp. 3996 - 4013 (2021)

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Chuzel, L.; Fossa, S. L.; Boisvert, M. L.; Cajic, S.; Hennig, R.; Ganatra, M. B.; Reichl, U.; Rapp, E.; Taron, C. H.: Combining functional metagenomics and glycoanalytics to identify enzymes that facilitate structural characterization of sulfated N-glycans. Microbial Cell Factories 20 (20), 162 (2021)

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De Vrieze, J.; Heyer, R.; Props, R.; Van Meulebroek, L.; Gille, K.; Vanhaecke, L.; Benndorf, D.; Boon, N.: Triangulation of microbial fingerprinting in anaerobic digestion reveals consistent fingerprinting profiles. Water Research 202 (1), 117422 (2021)

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Di Marco, F.; Berger, T.; Esser-Skala, W.; Rapp, E.; Regl, C.; Huber, C. G.: Simultaneous Monitoring of Monoclonal Antibody Variants by Strong Cation-Exchange Chromatography Hyphenated to Mass Spectrometry to Assess Quality Attributes of Rituximab-Based Biotherapeutics. International Journal of Molecular Sciences 22 (16), 9072 (2021)

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Eussen, S. R. B. M.; Mank, M.; Kottler, R.; Hoffmann, X.-K.; Behne, A.; Rapp, E.; Stahl, B.; Mearin, M. L.; Koletzko, B.: Presence and Levels of Galactosyllactoses and Other Oligosaccharides in Human Milk and Their Variation during Lactation and According to Maternal Phenotype. Nutrients 13 (7), 2324 (2021)

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Feichtinger, R. G.; Hüllen, A.; Koller, A.; Kotzot, D.; Grote, V.; Rapp, E.; Hofbauer, P.; Brugger, K.; Thiel, C.; Mayr, J. A. et al.; Wortmann, S. B.: A spoonful of L‐fucose—an efficient therapy for GFUS‐CDG, a new glycosylation disorder. Embo Molecular Medicine 13 (9), e14332 (2021)

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Fortuna, A. R.; Taft, F.; Villain, L.; Wolff, M. W.; Reichl, U.: Continuous purification of influenza A virus particles using pseudo-affinity membrane chromatography. Journal of Biotechnology 342, pp. 139 - 148 (2021)

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Gränicher, G.; Babakhani, M.; Göbel, S.; Jordan, I.; Marichal-Gallardo, P.; Genzel, Y.; Reichl, U.: A high cell density perfusion process for Modified Vaccinia virus Ankara production: process integration with inline DNA digestion and cost analysis. Biotechnology and Bioengineering 118 (12), pp. 4720 - 4734 (2021)

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Gränicher, G.; Tapia, F.; Behrendt, I.; Jordan, I.; Genzel, Y.; Reichl, U.: Production of Modified Vaccinia Ankara Virus by Intensified Cell Cultures: A Comparison of Platform Technologies for Viral Vector Production. Biotechnology Journal 16 (1), e2000024 (2021)

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Gücüm, S.; Sakson, R.; Hoffmann, M.; Grote, V.; Becker, C.; Pakari, K.; Beedgen, L.; Thiel, C.; Rapp, E.; Ruppert, T. et al.; Thumberger, T.; Wittbrodt, J.: A patient-based medaka alg2 mutant as a model for hypo-N-glycosylation. Development 148 (11), dev199385 (2021)

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Hassa, J.; Klang, J.; Benndorf, D.; Pohl, M.; Hülsemann, B.; Mächtig, T.; Effenberger, M.; Pühler, A.; Schlüter, A.; Theuerl, S.: Indicative Marker Microbiome Structures Deduced from the Taxonomic Inventory of 67 Full-Scale Anaerobic Digesters of 49 Agricultural Biogas Plants. Microorganisms 9 (7), 1457 (2021)

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Hein, M. D.; Arora, P.; Marichal-Gallardo, P.; Winkler, M.; Genzel, Y.; Pöhlmann, S.; Schughart, K.; Kupke, S. Y.; Reichl, U.: Cell culture-based production and in vivo characterization of purely clonal defective interfering influenza virus particles. BMC Biology 19 (1), 91 (2021)

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Hein, M. D.; Chawla, A.; Cattaneo, M.; Kupke, S. Y.; Genzel, Y.; Reichl, U.: Cell culture–based production of defective interfering influenza A virus particles in perfusion mode using an alternating tangential flow filtration system. Applied Microbiology and Biotechnology 105, pp. 7251 - 7264 (2021)

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Hein, M. D.; Kollmus, H.; Marichal-Gallardo, P.; Püttker, S.; Benndorf, D.; Genzel, Y.; Schughart, K.; Kupke, S. Y.; Reichl, U.: OP7, a novel influenza A virus defective interfering particle: production, purification, and animal experiments demonstrating antiviral potential. Applied Microbiology and Biotechnology 105, pp. 129 - 146 (2021)

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Kawahara, R.; Chernykh, A.; Alagesan, K.; Bern, M.; Cao, W.; Chalkley, R. J.; Cheng, K.; Choo, M. S.; Edwards, N.; Goldman, R. et al.; Hoffmann, M.; Hu, Y.; Huang, Y.; Kim, J. Y.; Kletter, D.; Liquet, B.; Liu, M.; Mechref, Y.; Meng, B.; Neelamegham, S.; Nguyen-Khuong, T.; Nilsson, J.; Pap, A.; Park, G. W.; Parker, B. L.; Pegg, C. L.; Penninger, J. M.; Phung, T. K.; Pioch, M.; Rapp, E.; Sakalli, E.; Sanda, M.; Schulz, B. L.; Scott, N. E.; Sofronov, G.; Stadlmann, J.; Vakhrushev, S. Y.; Woo, C. M.; Wu, H.-Y.; Yang, P.; Ying, W.; Zhang, H.; Zhang, Y.; Zhao, J.; Zaia, J.; Haslam, S. M.; Palmisano, G.; Yoo, J. S.; Larson, G.; Khoo, K.-H.; Medzihradszky, K. F.; Kolarich, D.; Packer, N. H.; Thaysen-Andersen, M.: Community evaluation of glycoproteomics informatics solutions reveals high-performance search strategies for serum glycopeptide analysis. Nature Methods 18, pp. 1304 - 1316 (2021)

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Lebede, M.; Di Marco, F.; Esser-Skala, W.; Hennig, R.; Wohlschlager, T.; Huber, C. G.: Exploring the Chemical Space of Protein Glycosylation in Noncovalent Protein Complexes: An Expedition along Different Structural Levels of Human Chorionic Gonadotropin by Employing Mass Spectrometry. Analytical Chemistry 93, pp. 10424 - 10434 (2021)

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Litschko, C.; Budde, I.; Berger, M.; Bethe, A.; Schulze, J.; Alcala Orozco, E. A.; Mahour, R.; Goettig, P.; Führing, J. I.; Rexer, T. et al.; Gerardy-Schahn, R.; Schubert, M.; Fiebig, T.: Mix-and-Match System for the Enzymatic Synthesis of Enantiopure Glycerol-3-Phosphate-Containing Capsule Polymer Backbones from Actinobacillus pleuropneumoniae, Neisseria meningitidis, and Bibersteinia trehalosi. mBio 12 (3), e00897-21 (2021)

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Mahour, R.; Lee, J. W.; Grimpe, P.; Boecker, S.; Grote, V.; Klamt, S.; Seidel-Morgenstern, A.; Rexer, T.; Reichl, U.: Cell‐free multi‐enzyme synthesis and purification of uridine diphosphate galactose. Chembiochem (2021)

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Mahour, R.; Marichal-Gallardo, P.; Rexer, T.; Reichl, U.: Multi-enzyme cascades for the in vitro synthesis of guanosine diphosphate L-fucose. ChemCatChem 13 (8), pp. 1981 - 1989 (2021)

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Marichal-Gallardo, P.; Börner, K.; Pieler, M.; Sonntag-Buck, V.; Obr, M.; Bejarano, D.; Wolff, M. W.; Kräusslich, H.-G.; Reichl, U.; Grimm, D.: Single-use capture purification of adeno-associated viral gene transfer vectors by membrane-based steric exclusion chromatography. Human Gene Therapy 32 (17-18), pp. 959 - 974 (2021)

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Meinusch, N.; Kramer, S.; Körner, O.; Wiese, J.; Seick, I.; Beblek, A.; Berges, R.; Illenberger, B.; Illenberger, M.; Uebbing, J. et al.; Wolf, M.; Saake, G.; Benndorf, D.; Reichl, U.; Heyer, R.: Integrated Cycles for Urban Biomass as a Strategy to Promote a CO2-Neutral Society—A Feasibility Study. Sustainability 13 (17), 9505 (2021)

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Noor, S. I.; Hoffmann, M.; Rinis, N.; Bartels, M. F.; Winterhalter, P. R.; Hoelscher, C.; Hennig, R.; Himmelreich, N.; Thiel, C.; Ruppert, T. et al.; Rapp, E.; Strahl, S.: Glycosyltransferase POMGNT1 deficiency strengthens N-cadherin-mediated cell-cell adhesion. Journal of Biological Chemistry, 100433 (2021)

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Offersgaard, A.; Duarte Hernandez, C. R.; Pihl, A. F.; Costa, R.; Venkatesan, N. P.; Lin, X.; Van Pham, L.; Feng, S.; Fahnøe, U.; Scheel, T. K. H. et al.; Ramirez, S.; Reichl, U.; Bukh, J.; Genzel, Y.; Gottwein, J. M.: SARS-CoV-2 Production in a Scalable High Cell Density Bioreactor. Vaccine 9 (7), 706 (2021)

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Patenaude, A.; Erhardt, J.; Hennig, R.; Rapp, E.; Lauc, G.; Pezer, M.: N‐glycosylation analysis of mouse immunoglobulin G isolated from dried blood spots. Electrophoresis: Special Issue: Monoliths 2021 42 (24), pp. 2615 - 2618 (2021)

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Pech, S.; Rehberg, M.; Janke, R.; Benndorf, D.; Genzel, Y.; Muth, T.; Sickmann, A.; Rapp, E.; Reichl, U.: Tracking changes in adaptation to suspension growth for MDCK cells: cell growth correlates with levels of metabolites, enzymes and proteins. Applied Microbiology and Biotechnology 105, pp. 1861–1874 - 1874 (2021)

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Pelz, L.; Rüdiger, D.; Dogra, T.; Alnaji, F. G.; Genzel, Y.; Brooke, C. B.; Kupke, S. Y.; Reichl, U.: Semi-continuous propagation of influenza A virus and its defective interfering particles: analyzing the dynamic competition to select candidates for antiviral therapy. Journal of Virology 95 (24), e01174-21 (2021)

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Pralow, A.; Hoffmann, M.; Nguyen-Khuong, T.; Pioch, M.; Hennig, R.; Genzel, Y.; Rapp, E.; Reichl, U.: Comprehensive N‐glycosylation analysis of the influenza A virus proteins HA and NA from adherent and suspension MDCK cells. The FEBS Journal 288 (16), pp. 4869 - 4891 (2021)

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Pralow, A.; Nikolay, A.; Leon, A.; Genzel, Y.; Rapp, E.; Reichl, U.: Site-specific N-glycosylation analysis of animal cell culture-derived Zika virus proteins. Scientific Reports 11, 5147 (2021)

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Puan, K. J.; San Luis, B.; Yusof, N.; Kumar, D.; Andiappan, A. K.; Lee, W.; Cajic, S.; Vuckovic, D.; Chan, J. D.; Döllner, T. et al.; Hou, H. W.; Jiang, Y.; Tian, C.; Agee, M.; Aslibekyan, S.; Auton, A.; Babalola, E.; Bell, R. K.; Bielenberg, J.; Bryc, K.; Bullis, E.; Cameron, B.; Coker, D.; Partida, G. C.; Dhamija, D.; Das, S.; Elson, S. L.; Filshtein, T.; Fletez-Brant, K.; Fontanillas, P.; Freyman, W.; Gandhi, P. M.; Heilbron, K.; Hicks, B.; Hinds, D. A.; Huber, K. E.; Jewett, E. M.; Kleinman, A.; Kukar, K.; Lane, V.; Lin, K.-H.; Lowe, M.; Luff, M. K.; McCreight, J. C.; McIntyre, M. H.; McManus, K. F.; Micheletti, S. J.; Moreno, M. E.; Mountain, J. L.; Mozaffari, S. V.; Nandakumar, P.; Noblin, E. S.; O’Connell, J.; Petrakovitz, A. A.; Poznik, G. D.; Schumacher, M.; Shastri, A. J.; Shelton, J. F.; Shi, J.; Shringarpure, S.; Tran, V.; Tung, J. Y.; Wang, X.; Wang, W.; Weldon, C. H.; Wilton, P.; Rapp, E.; Poidinger, M.; Wang, D. Y.; Soranzo, N.; Lee, B.; Rötzschke, O.: FUT6 deficiency compromises basophil function by selectively abrogating their sialyl-Lewis x expression. Communications Biology 4, 832 (2021)

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Rand, U.; Kupke, S. Y.; Shkarlet, H.; Hein, M. D.; Hirsch, T.; Marichal-Gallardo, P.; Cicin-Sain, L.; Reichl, U.; Bruder, D.: Antiviral Activity of Influenza A Virus Defective Interfering Particles against SARS-CoV-2 Replication In Vitro through Stimulation of Innate Immunity. Cells 10 (7), 1756 (2021)

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Reichl, U.; Seidel-Morgenstern, A.; Sundmacher, K.; Tsotsas, E.; van Wachem, B.: Forschungsarbeiten am Institut für Verfahrenstechnik der Otto‐von‐Guericke‐Universität Magdeburg. Chemie Ingenieur Technik 93 (3), pp. 345 - 352 (2021)

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Rüdiger, D.; Pelz, L.; Hein, M. D.; Kupke, S. Y.; Reichl, U.: Multiscale model of defective interfering particle replication for influenza A virus infection in animal cell culture. PLoS Computational Biology 17, e1009357 (2021)

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Ruhnau, J.; Grote, V.; Juarez-Osorio, M.; Bruder, D.; Mahour, R.; Rapp, E.; Rexer, T.; Reichl, U.: Cell-Free Glycoengineering of the Recombinant SARS-CoV-2 Spike Glycoprotein. Frontiers in Bioengineering and Biotechnology 9, 699026 (2021)

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Starke, R.; Siles, J. A.; Fernandes, M. L. P.; Schallert, K.; Benndorf, D.; Plaza, C.; Jehmlich, N.; Delgado-Baquerizo, M.; Bastida, F.: The structure and function of soil archaea across biomes. Journal of Proteomics 237, 104147 (2021)

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Van Den Bossche, T.; Arntzen, M. Ø.; Becher, D.; Benndorf, D.; Eijsink, V. G. H.; Henry, C.; Jagtap, P. D.; Jehmlich, N.; Juste, C.; Kunath, B. J. et al.; Mesuere, B.; Muth, T.; Pope, P. B.; Seifert, J.; Tanca, A.; Uzzau, S.; Wilmes, P.; Hettich, R. L.; Armengaud, J.: The Metaproteomics Initiative: a coordinated approach for propelling the functional characterization of microbiomes. Microbiome 9 (1), 243 (2021)

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Van Den Bossche, T.; Kunath, B. J.; Schallert, K.; Schäpe, S. S.; Abraham, P. E.; Armengaud, J.; Arntzen, M. Ø.; Bassignani, A.; Benndorf, D.; Fuchs, S. et al.; Giannone, R. J.; Griffin, T. J.; Hagen, L. H.; Halder, R.; Henry, C.; Hettich, R. L.; Heyer, R.; Jagtap, P.; Jehmlich, N.; Jensen, M.; Juste, C.; Kleiner, M.; Langella, O.; Lehmann, T.; Leith, E.; May, P.; Mesuere, B.; Miotello, G.; Peters, S. L.; Pible, O.; Reichl, U.; Renard, B. Y.; Schiebenhoefer, H.; Scryba, A.; Tanca, A.; Trappe, K.; Trezzi, J.-P.; Uzzau, S.; Verschaffelt, P.; von Bergen, M.; Wilmes, P.; Wolf, M.; Martens, L.; Muth, T.: Critical Assessment of Metaproteome Investigation (CAMPI): A Multi-Lab Comparison of Established Workflows. Nature Communications 12 (1), 7305 (2021)

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Walke, D.; Schallert, K.; Ramesh, P.; Benndorf, D.; Lange, E.; Reichl, U.; Heyer, R.: MPA_Pathway_Tool: User-Friendly, Automatic Assignment of Microbial Community Data on Metabolic Pathways. International Journal of Molecular Sciences 22 (20), 10992 (2021)

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Wu, Y.; Bissinger, T.; Genzel, Y.; Liu, X.; Reichl, U.; Tan, W.-S.: High cell density perfusion process for high yield of influenza A virus production using MDCK suspension cells. Applied Microbiology and Biotechnology 105 (4), pp. 1421 - 1434 (2021)

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2020

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Coronel, J.; Gränicher, G.; Sandig, V.; Noll, T.; Genzel, Y.; Reichl, U.: Application of an Inclined Settler for Cell Culture-Based Inﬂuenza A Virus Production in Perfusion Mode. Frontiers in Bioengineering and Biotechnology 8, 672 (2020)

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Duvigneau, S.; Dürr, R.; Laske, T.; Bachmann, M.; Dostert, M.; Kienle, A.: Model-based approach for predicting the impact of genetic modifications on product yield in biopharmaceutical manufacturing—Application to influenza vaccine production. PLoS Computational Biology 16 (6), e1007810 (2020)

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Gränicher, G.; Coronel, J.; Trampler, F.; Jordan, I.; Genzel, Y.; Reichl, U.: Performance of an Acoustic Settler Versus a Hollow Fiber-Based ATF Technology for Influenza Virus Production in Perfusion. Applied Microbiology and Biotechnology 104, pp. 4877 - 4888 (2020)

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Heyer, R.; Klang, J.; Hellwig, P.; Schallert, K.; Kress, P.; Huelsemann, B.; Theuerl, S.; Reichl, U.; Benndorf, D.: Impact of feeding and stirring regimes on the internal stratification of microbial communities in the fermenter of anaerobic digestion plants. Bioresource Technology 314, 123679 (2020)

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Hinneburg , H.; Pedersen, J. L.; Bokil, N. J.; Pralow, A.; Schirmeister, F.; Kawahara, R.; Rapp, E.; Saunders, B. M.; Thaysen-Andersen, M.: High-resolution Longitudinal N- And O-glycoprofiling of Human Monocyte-To- Macrophage Transition. Glycobiology 30 (9), pp. 679 - 694 (2020)

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Kupke, S. Y.; Ly, L.-H.; Börno, S. T.; Ruff, A.; Timmermann, B.; Vingron, M.; Haas , S.; Reichl, U.: Single-Cell Analysis Uncovers a Vast Diversity in Intracellular Viral Defective Interfering RNA Content Affecting the Large Cell-to-Cell Heterogeneity in Influenza A Virus Replication. Viruses 12 (1), 71 (2020)

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Leoz, D.; A., M. L.; Duewer, D. L.; Fung, A.; Liu, L.; Yau, H. K.; Potter, O.; Staples, G. O.; Furuki, K.; Frenkel, R. et al.; Hu, Y.; Sosic, Z.; Zhang, P.; Altmann, F.; Gruber, C.; Shao, C.; Zaia, J.; Evers, W.; Pangelley, S.; Suckau, D.; Wiechmann, A.; Resemann, A.; Jabs, W.; Beck, A.; Froehlich, J. W.; Huang, C.; Li, Y.; Liu, Y.; Sun, S.; Wang, Y.; Seo, Y.; An, H. J.; Reichardt, N.-C.; Ruiz, J. E.; Archer‑Hartmann, S.; Azadi, P.; Bell, L.; Lakos, Z.; An, Y.; Cipollo, J. F.; Pučić-Baković, M.; Štambuk, J.; Lauc, G.; Li, X.; Wang, P. G.; Bock, A.; Hennig, R.; Rapp, E.; Creskey, M.; Cyr, T.; Nakano, M.; Sugiyama, T.; Leung, P. A.; Link‑Lenczowski, P.; Jaworek, J.; Yang, S. J.; Zhang, H.; Kelly, T.; Klapoetke, S.; Cao, R.; Kim, J. Y.; Lee, H. K.; Lee, J.; Yoo, J. S.; Kim, S.; Suh, S.; de Haan, N.; Falck, D.; Lageveen-Kammeijer, G. S.M.; Wuhrer, M.; Emery, R. J.; Kozak, R. P.; Liew, L. P.; Royle, L.; Urbanowicz, P. A.; Packer, N.; Song, X.; Everest-Dass, A.; Lattová, E.; Cajic, S.; Alagesan, K.; Kolarich, D.; Kasali, T.; Lindo, V.; Chen, Y.; Goswami, K.; Gau, B.; Amunugama, R.; Jones, R.; Stroop, C. J. M.; Kato, K.; Yagi, H.; Kondo, S.; Yuen, C.; Harazono, A.; Shi, X.; Magnelli, P.; Kasper, B. T.; Mahal, L. K.; Harvey, D. J.; O'Flaherty, R.; Rudd, P. M.; Saldova, R.; Hecht, E. S.; Muddiman, D. C.; Kang, J.; Bhoskar, P.; Menard, D.; Saati, A.; Merle, C.; Mast, S.; Tep, S.; Truong, J.; Nishikaze, T.; Sekiya, S.; Shafer, A.; Funaoka, S.; Toyoda, M.; de Vreugd, P.; Caron, C.; Pradhan, P.; Tan, N. C.; Mechref, Y.; Patil, S.; Rohrer, J. S.; Chakrabarti, R.; Dadke, D.; Lahori, M.; Zou, C.; Cairo, C. W.; Reiz, B.; Whittal, R. M.; Lebrilla, C.; Wu, L. D.; Guttman, A.; Szigeti, M.; Kremkow, B. G.; Lee, K.; Sihlbom, C.; Adamczyk, B.; Jin, C.; Karlsson, N. G.; Örnros, J.; Larson, G.; Nilsson, J.; Meyer, B.; Wiegandt, A.; Komatsu, E.; Perreault, H.; Bodnar, E. D.; Said, N.; Francois, Y.; Leize-Wagner, E.; Maier, S.; Zeck, A.; Heck, A. J. R.; Yang, Y.; Haselberg, R.; Yu, Y. Q.; Alley, W.; Leone, J. W.; Yuan, H.; Stein, S. E.: NIST interlaboratory study on glycosylation analysis of monoclonal antibodies: comparison of results from diverse analytical methods. Molecular and Cellular Proteomics 19 (1), pp. 11 - 30 (2020)

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Maus, I.; Tubbesing, T.; Wibberg, D.; Heyer, R.; Hassa, J.; Tomazetto, G.; Huang, L.; Bunk, B.; Spröer, C.; Benndorf, D. et al.; Zverlov, V.; Pühler, A.; Klocke, M.; Sczyrba, A.; Schlüter, A.: The Role of Petrimonas mucosa ING2-E5AT in Mesophilic Biogas Reactor Systems as Deduced from Multiomics Analyses. Microorganisms 8 (12), 2024 (2020)

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Nikolay, A.; de Grooth, J.; Genzel, Y.; Wood, J. A.; Reichl, U.: Virus harvesting in perfusion culture: Choosing the right typeof hollow fiber membrane. Biotechnology and Bioengineering 117 (10), pp. 3040 - 3052 (2020)

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Publications BPE group

Journal Article (300)