Oxidized and Aggregated Recombinant Human Interferon Beta is Immunogenic in Human Interferon Beta Transgenic Mice

PurposeTo study the effect of oxidation on the structure of recombinant human interferon beta-1a (rhIFNβ-1a) and its immunogenicity in wild-type and immune-tolerant transgenic mice.MethodsUntreated rhIFNβ-1a was degraded by metal-catalyzed oxidation, H2O2-mediated oxidation, and guanidine-mediated unfolding/refolding. Four rhIFNβ-1a preparations with different levels of oxidation and aggregation were injected intraperitoneally in mice 15× during 3 weeks. Both binding and neutralizing antibodies were measured.ResultsAll rhIFNβ-1a preparations contained substantial amounts of aggregates. Metal-catalyzed oxidized rhIFNβ-1a contained high levels of covalent aggregates as compared with untreated rhIFNβ-1a. H2O2-treated rhIFNβ-1a showed an increase in oligomer and unrecovered protein content by HP-SEC; RP-HPLC revealed protein oxidation. Guanidine-treated rhIFNβ-1a mostly consisted of dimers and oligomers and some non-covalent aggregates smaller in size than those in untreated rhIFNβ-1a. All degraded samples showed alterations in tertiary protein structure. Wild-type mice showed equally high antibody responses against all preparations. Transgenic mice were discriminative, showing elevated antibody responses against both metal-catalyzed oxidized and H2O2-treated rhIFNβ-1a as compared to untreated and guanidine-treated rhIFNβ-1a.ConclusionsOxidation-mediated aggregation increased the immunogenicity of rhIFNβ-1a in transgenic mice, whereas aggregated preparations devoid of measurable oxidation levels were hardly immunogenic

A knowledge-based decision support framework for wave put-away operations of e-commerce and O2O shipments

2016 6th International Workshop of Advanced Manufacturing and Automation (IWAMA2016), University of Manchester, UK, 10 -11 November 2016202402 bcchVersion of RecordRGCPublishedC

A Knowledge-based Decision Support Framework for Wave Put-away Operations of E-commerce and O2O Shipments

Department of Industrial and Systems Engineerin

Klebsiella variicola

ABSTRACTThe Klebsiella pneumoniae complex comprises seven K. pneumoniae-related species, including K. variicola. K. variicola is a versatile bacterium capable of colonizing different hosts such as plants, humans, insects and animals. Currently, K. variicola is gaining recognition as a cause of several human infections; nevertheless, its virulence profile is not fully characterized. The clinical significance of K. variicola infection is hidden by imprecise detection methods that underestimate its real prevalence; however, several methods have been developed to correctly identify this species. Recent studies of carbapenemase-producing and colistin-resistant strains demonstrate a potential reservoir of multidrug-resistant genes. This finding presents an imminent scenario for spreading antimicrobial resistant genes among close relatives and, more concerningly, in clinical and environmental settings. Since K. variicola was identified as a novel bacterial species, different research groups have contributed findings elucidating this pathogen; however, important details about its epidemiology, pathogenesis and ecology are still missing. This review highlights the most significant aspects of K. variicola, discussing its different phenotypes, mechanisms of resistance, and virulence traits, as well as the types of infections associated with this pathogen