To enter host cells, vaccinia virus, a prototype poxvirus, can induce transient macropinocytosis followed by endocytic internalization and penetration through the limiting membrane of pinosomes by membrane fusion. Although mature virions (MVs) of the Western reserve (WR) strain do this in HeLa cells by activating transient plasma membrane blebbing, MVs from the International Health Department-J strain were found to induce rapid formation (and lengthening) of filopodia. When the signaling pathways underlying these responses were compared, differences were observed at the level of Rho GTPases. Key to the filopodial formation was the virus-induced activation of Cdc42, and for the blebbing response the activation of Rac1. In addition, unlike WR, International Health Department-J MVs did not rely on genistein-sensitive tyrosine kinase and PI(3)K activities. Only WR MVs had membrane fusion activity at low pH. Inhibitor profiling showed that MVs from both strains entered cells by macropinocytosis and that this was induced by virion-exposed phosphatidylserine. Both MVs relied on the activation of epidermal growth factor receptor, on serine/ threonine kinases, protein kinase C, and p21-activated kinase 1. The results showed that different strains of the same virus can elicit dramatically different responses in host cells during entry, and that different macropinocytic mechanisms are possible in the same cell line through subtle differences in the activating ligand.epidermal growth factor receptor | endocytosis | poxvirus | Rho GTPases | virus entry
The purpose of this paper is to provide new insights in the field of operations management decision-finding. It aims to combine manufacturing strategies with the service dominant logic in order to connect customer satisfaction. An analytic hierarchy process (AHP) is developed and applied within two case companies. A sensitivity analysis revealed that the manufacturing strategy selection changes when customer requirements vary. The sensitivity of manufacturing strategy alteration towards changing customer requirements is dependent on distinct product characteristics. The presented AHP offers an opportunity to define those customer requirements predominantly affecting manufacturing strategy selection. The paper provides a helpful generic framework that could serve as starting point to develop appropriate supply chain differentiation approaches.
The purpose of this paper is to provide new evidence in the field of supply chain differentiation. It aims to combine insights of supply chain management with the service dominant logic to connect fundamental customer requirements with supply chain decision-making. The paper claims to provide a framework that brings together the most relevant factors in the context of supply chain differentiation. The contents of the framework were applied as source to develop a generic decision support flowchart for supply chain executives. From the perspective of "test consumers"-supplemented with secondary data-two cases were examined. The cases provide insights for supply chain differentiation approaches of Adidas and Lego ® . The crucial factor to link customer requirements with supply chain settings turned out to be the magnitude of customer co-creation along the value chain under consideration of synergies across the channels. The framework provides the opportunity to structure the complex multi-criteria decision problem constituted by supply chain differentiation. The paper provides helpful insights that could be used as starting point for the development of several industry specific decision-finding models or applications in supply chain differentiation.
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