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Cancer therapy that utilizes oncolytic virus may offer an exciting alternative, and coxsackievirus B3 (CVB3) is a potent oncolytic virus. This study was to assess the oncolytic activities of novel recombinant CVB3 with genetically inserted basic peptides in lung cancer. Recombinant CVB3 was produced in Vero cells, with or without genetically inserted basic peptides. In vitro and in vivo experiments with nude mouse models bearing human lung carcinoma xenografts were performed to examine the antitumor activities. Cytokines and immune responses to the recombinant CVB3 were determined in cynomolgus monkeys. Recombinant CVB3 with genetically inserted basic peptides was associated with significantly higher pH values within tumors. Mice treated with recombinant CVB3 showed significantly less tumor progression, and recombinant CVB3 with genetically inserted basic peptides appeared to enhance tumor suppression. Recombinant CVB3 was associated with significantly less proliferation of various lung cancer cells without affecting proliferation of normal lung fibroblasts. The cytokine profiles of the cynomolgus monkeys were comparable among control group (normal saline solution) and those given recombinant CVB3 with or without fused basic peptides, with no induction of excessive cytokine or immune responses. In conclusions, recombinant CVB3, especially those with fused basic peptides, possess strong antitumor activities without eliciting excessive immune responses. [ABSTRACT FROM AUTHOR]

Robust design (RD) is an important method because it can reduce the variation of products or processes and improve their performances such as static and dynamic quality characteristics at a low cost. In order to obtain an efficient and universal RD solution, a novel analytical RD methodology is proposed based on axiomatic design principles. The covariance matrix of multiple functional requirements (FRs) that can reflect dependency relationship is obtained via the Talyor series expansion. Evaluation mechanism based on information axiom is introduced to select the better design scheme gained with different robust optimization models. The distinct characteristics of the proposed method are the implementation by matrix differential, and the ability that can deal with multiple FR optimization simultaneously. An RD optimization of a five roller coating head is illustrated. The results show that the proposed method can optimize the design parameters which meet the multiple FRs. Copyright © 2013 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]