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Pejnovic, N.,Vratimos, A.,Lee, S.H.,Popadic, D.,Takeda, K.,Akira, S.,Chan, W.L. Pergamon Press 2009 Molecular immunology Vol.47 No.1
Recent reports show T helper 17 (Th17) cells are involved in the pathogenesis of various chronic inflammatory diseases formerly categorized as Th1-mediated disorders. Interleukin-18 (IL-18) induces Th1 cells to produce interferon-γ (IFN-γ) which is proatherogenic, while cholesterol causes atherosclerosis and stimulates intact rat aortae to produce prostaglandin E<SUB>2</SUB> (PGE<SUB>2</SUB>), a strong regulator of IL-23 that expands Th17. We wanted to test whether Th17 is proatherogenic and whether cholesterol can induce the alternative Th17 pathway in IL-18 deficient apolipoprotein E-knockout (ApoE<SUP>-/-</SUP>) mice that have reduced Th1 cells, if they are fed high-cholesterol diet. IL-18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> and IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice aged 5 weeks were fed high-cholesterol diet (HCD) and control littermates of IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> low-cholesterol diet (LCD) for 12 weeks. At termination, cryosectioned aortic arches were stained for lesion measurement and immunohistochemistry. We found that serum cholesterol and triglyceride levels were significantly higher in IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice on HCD and they also had significantly increased atherosclerosis compared with 18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> mice or IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> mice on LCD. Increased atherosclerosis correlates with enhanced Th17-cells, IL-23-producing vascular smooth muscle cells (VSMC) and macrophages, and thin fibrous cap in lesions, the morphology indicative of unstable plaques prone to rupture. In vitro, cholesterol significantly enhances VSMCs explanted from IL-18<SUP>-/-</SUP>ApoE<SUP>-/-</SUP> but not IL-18<SUP>+/+</SUP>ApoE<SUP>-/-</SUP> aorta to produce IL-23 and homocysteine mediates secretion. This study suggests that in IL-18 deficiency, cholesterol in HCD synergize mechanistically with homocysteine to accelerate atherosclerosis via the alternative IL-23/Th17 pathway, demonstrating a new role for Th17 in atherosclerosis.
Nishikawa, M.,Okabe, T.,Takeda, N. The Korean Society for Composite Materials 2009 Advanced composite materials Vol.18 No.1
This paper investigated the damage transition mechanism between the fiber-breaking mode and the fiber-avoiding crack mode when the fiber-length is reduced in the unidirectional discontinuous carbon fiber-reinforced-plastics (CFRP) composites. The critical fiber-length for the transition is a key parameter for the manufacturing of flexible and high-strength CFRP composites with thermoset resin, because below this limit, we cannot take full advantage of the superior strength properties of fibers. For this discussion, we presented a numerical model for the microscopic damage and fracture of unidirectional discontinuous fiber-reinforced plastics. The model addressed the microscopic damage generated in these composites; the matrix crack with continuum damage mechanics model and the fiber breakage with the Weibull model for fiber strengths. With this numerical model, the damage transition behavior was discussed when the fiber length was varied. The comparison revealed that the length of discontinuous fibers in composites influences the formation and growth of the cluster of fiber-end damage, which causes the damage mode transition. Since the composite strength is significantly reduced below the critical fiber-length for the transition to fiber-avoiding crack mode, we should understand the damage mode transition appropriately with the analysis on the cluster growth of fiber-end damage.
Yashiro, S.,Murai, K.,Okabe, T.,Takeda, N. The Korean Society for Composite Materials 2007 Advanced composite materials Vol.16 No.2
This study proposes two new approaches for identifying damage patterns in a holed CFRP cross-ply laminate using an embedded fiber Bragg grating (FBG) sensor. It was experimentally confirmed that the reflection spectrum from the embedded FBG sensor was significantly deformed as the damage near the hole (i.e. splits, transverse cracks and delamination) extended. The damage patterns were predicted using forward analysis (a damage analysis and an optical analysis) with strain estimation and the proposed damage-identification method as well as the forward analysis only. Forward analysis with strain estimation provided the most accurate damage-pattern estimation and the highest computational efficiency. Furthermore, the proposed damage identification significantly reduced computation time with the equivalent accuracy compared to the conventional identification procedure, by using damage analysis as the initial estimation.