Purpose-Rail corrugation is still one of the unsolved challenges in the railway industry,and the abnormal vibration and high-frequency noise caused by it constitute serious adverse effects on the operating environment...Purpose-Rail corrugation is still one of the unsolved challenges in the railway industry,and the abnormal vibration and high-frequency noise caused by it constitute serious adverse effects on the operating environment.How to control corrugation has been an important research theme,and understanding corrugation evolution features is the necessary prerequisite.This study aims to investigate the specific evolution characteristics of corrugation from the contact stick-slip perspective.Design/methodology/approach-The formation and development processes of corrugation are analyzed by using a self-designed scale-down test device.Specifically,the contact stick-slip characteristics under different creepage conditions are analyzed and the formation mechanism of corrugation is summarized.On the basis of corrugation formation,the trend of corrugation development is further emphasized to completely describe the whole process of corrugation evolution.Findings-The results show that,under the determined vertical load condition,the contact interface appears the creep force-creepage negative slope phenomenon in the transverse direction.The cause of short-pitch corrugation on the rail wheel surface under the smaller angles of attack may be related to the inherent vibration frequency of the test device,and the cause of corrugation on the rail wheel surface under the larger angles of attack is mainly related to the stick-slip vibration induced by contact creep saturation.Originality/value-This research explores the evolution characteristics of corrugation by adopting a selfdesigned scale-down test device,and elucidates the mechanism of corrugation in detail.展开更多
Bioprocess scale-down simulators are used to investigate the phenomena occurring in industrial scale cultivations. The aim is to simulate the large-scale conditions, characterized by long mixing times introducing loca...Bioprocess scale-down simulators are used to investigate the phenomena occurring in industrial scale cultivations. The aim is to simulate the large-scale conditions, characterized by long mixing times introducing local gradients into the bioreactor, in laboratory scale bioreactor. We have expanded the current physiological knowledge about the consequences of such cultivation conditions from well-known mixed-acid fermentation to amino acid metabolism. Several interesting deviations were observed for amino acids derived from pyruvate when a STR-PFR scale-down simulator and a regular STR fed-batch cultivation were compared. In this article we show that the cultivation of Escherichia coli K-12 substrain W3110 in a scale-down two-compartment bioreactor has consequences on the free amino acid pools. Repeated occurrence of high glucose zones affects the biosynthesis of amino acids derived from pyruvate. This is interesting since the pyruvate based amino acids are precursors of the branched chain amino acid pathway, which is further disturbed by an unbalanced regulation caused by a frameshift mutation in the ilvG gene of E. coli K-12 strains. As a consequence the formation of non-typical amino acid norvaline was detected in the two compartment bioreactor cultivation.展开更多
目的通过构建15 L缩小模型验证重组人干扰素(recombinant human interferon,rhIFN)α2b工作代菌种在关键代次的传代稳定性,以确保rhIFNα2b在生产过程中的稳定性和有效性。方法将rhIFNα2b冻干菌种复苏并进行传代培养,分别对第0、10、20...目的通过构建15 L缩小模型验证重组人干扰素(recombinant human interferon,rhIFN)α2b工作代菌种在关键代次的传代稳定性,以确保rhIFNα2b在生产过程中的稳定性和有效性。方法将rhIFNα2b冻干菌种复苏并进行传代培养,分别对第0、10、20、30、40、50代菌液保存甘油菌。选取传代稳定性研究中保存的各代次甘油菌样品,在模拟生产条件的15 L缩小模型发酵系统中进行发酵-表达试验,通过实时监测菌体生长曲线,结合终点检测指标(产物表达量、生物学活性、质粒稳定性、遗传完整性以及微生物纯度等)进行全面比对,以判断限传代次是否可覆盖现有培养工艺。结果rhIFNα2b工作代菌种第0、10、20、30、40和50代甘油菌在连续传代培养后,表现出良好的稳定性和一致性。各代次菌种在LB平板上均呈现典型的大肠埃希菌菌落形态,无杂菌污染;抗生素抗性未发生改变;革兰染色结果均为革兰阴性;生化反应特性符合大肠埃希菌典型特征;目标基因表达量始终高于20%,且无下降趋势;发酵活性维持在1.0×10^(8)IU/L以上;质粒酶切图谱与理论图谱一致,序列未发生变化,质粒丢失率<30%,表现出较好的遗传稳定性。结论rhIFNα2b工作代菌种在缩小模型模拟生产规模发酵时发酵培养的稳定性良好,现有工艺条件下菌种的限传代次能够有效覆盖变更后的生产需求,为工艺优化提供了重要的数据支撑。展开更多
基金funded by the Science and Technology Research Project of Universities in Hebei Province(No.QN2025314)Youth Specialization Fund for State Key Laboratory(No.50110010766)Shanghai Key Laboratory of Rail Infrastructure Durability and System Safety(No.R202405).
文摘Purpose-Rail corrugation is still one of the unsolved challenges in the railway industry,and the abnormal vibration and high-frequency noise caused by it constitute serious adverse effects on the operating environment.How to control corrugation has been an important research theme,and understanding corrugation evolution features is the necessary prerequisite.This study aims to investigate the specific evolution characteristics of corrugation from the contact stick-slip perspective.Design/methodology/approach-The formation and development processes of corrugation are analyzed by using a self-designed scale-down test device.Specifically,the contact stick-slip characteristics under different creepage conditions are analyzed and the formation mechanism of corrugation is summarized.On the basis of corrugation formation,the trend of corrugation development is further emphasized to completely describe the whole process of corrugation evolution.Findings-The results show that,under the determined vertical load condition,the contact interface appears the creep force-creepage negative slope phenomenon in the transverse direction.The cause of short-pitch corrugation on the rail wheel surface under the smaller angles of attack may be related to the inherent vibration frequency of the test device,and the cause of corrugation on the rail wheel surface under the larger angles of attack is mainly related to the stick-slip vibration induced by contact creep saturation.Originality/value-This research explores the evolution characteristics of corrugation by adopting a selfdesigned scale-down test device,and elucidates the mechanism of corrugation in detail.
文摘Bioprocess scale-down simulators are used to investigate the phenomena occurring in industrial scale cultivations. The aim is to simulate the large-scale conditions, characterized by long mixing times introducing local gradients into the bioreactor, in laboratory scale bioreactor. We have expanded the current physiological knowledge about the consequences of such cultivation conditions from well-known mixed-acid fermentation to amino acid metabolism. Several interesting deviations were observed for amino acids derived from pyruvate when a STR-PFR scale-down simulator and a regular STR fed-batch cultivation were compared. In this article we show that the cultivation of Escherichia coli K-12 substrain W3110 in a scale-down two-compartment bioreactor has consequences on the free amino acid pools. Repeated occurrence of high glucose zones affects the biosynthesis of amino acids derived from pyruvate. This is interesting since the pyruvate based amino acids are precursors of the branched chain amino acid pathway, which is further disturbed by an unbalanced regulation caused by a frameshift mutation in the ilvG gene of E. coli K-12 strains. As a consequence the formation of non-typical amino acid norvaline was detected in the two compartment bioreactor cultivation.
文摘目的通过构建15 L缩小模型验证重组人干扰素(recombinant human interferon,rhIFN)α2b工作代菌种在关键代次的传代稳定性,以确保rhIFNα2b在生产过程中的稳定性和有效性。方法将rhIFNα2b冻干菌种复苏并进行传代培养,分别对第0、10、20、30、40、50代菌液保存甘油菌。选取传代稳定性研究中保存的各代次甘油菌样品,在模拟生产条件的15 L缩小模型发酵系统中进行发酵-表达试验,通过实时监测菌体生长曲线,结合终点检测指标(产物表达量、生物学活性、质粒稳定性、遗传完整性以及微生物纯度等)进行全面比对,以判断限传代次是否可覆盖现有培养工艺。结果rhIFNα2b工作代菌种第0、10、20、30、40和50代甘油菌在连续传代培养后,表现出良好的稳定性和一致性。各代次菌种在LB平板上均呈现典型的大肠埃希菌菌落形态,无杂菌污染;抗生素抗性未发生改变;革兰染色结果均为革兰阴性;生化反应特性符合大肠埃希菌典型特征;目标基因表达量始终高于20%,且无下降趋势;发酵活性维持在1.0×10^(8)IU/L以上;质粒酶切图谱与理论图谱一致,序列未发生变化,质粒丢失率<30%,表现出较好的遗传稳定性。结论rhIFNα2b工作代菌种在缩小模型模拟生产规模发酵时发酵培养的稳定性良好,现有工艺条件下菌种的限传代次能够有效覆盖变更后的生产需求,为工艺优化提供了重要的数据支撑。
