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Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is known to have pivotal roles in various inflammatory processes. The TWEAK receptor, fibroblast growth factor-inducible 14 (Fn14), has various unique functions under physiological and pathological conditions; however, the therapeutic potential of its direct targeting remains unknown. Here, we found that Fn14 expression was highly upregulated in ischemic renal tissues and tubular epithelial cells of patient biopsies and experimental animal models of renal injury. To clarify the function of Fn14 in ischemia reperfusion injury, we coincubated renal tubular cells with ITEM-2, an anti-Fn14 blocking monoclonal antibody, and found that it inhibited the production of proinflammatory cytokines and chemokines after injury. Furthermore, Fn14 blockade downregulated the local expression of several proinflammatory mediators, reduced accumulation of neutrophils and macrophages in ischemic tissues, and inhibited tubular cell apoptosis. Importantly, Fn14 blockade attenuated the development of chronic fibrosis after ischemia reperfusion injury and significantly prolonged the survival of lethally injured mice. Thus, we conclude that Fn14 is a critical mediator in the pathogenesis of ischemia reperfusion injury.

The ␥ /␥ Ј interfacial dislocation networks in several creep-ruptured superalloys were analyzed. It was found that the morphologies of dislocation networks differ slightly from each other in these alloys. The fourth-generation superalloy has finer dislocation networks and keeps a relatively stable state. Comparatively, the interfacial dislocations in the third-generation superalloy show obvious curved features associated with possible climb or slip. These interfacial dislocation characteristics can be correlated with the creep behavior of these superalloys. The mechanisms of evolution of the interfacial dislocation networks were discussed.

The microstructure and compression strengths of Ir-15 at. pct X (X ϭ Ti, Ta, Nb, Hf, Zr, or V) binary alloys at temperatures between room temperature and 1800 ЊC were investigated to evaluate the potential of these alloys for ultra-high-temperature use. The fcc and L1 2 two-phase structures of these alloys were examined by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). The strengths of the Ir-Ta, -Nb, -Hf, and -Zr alloys were above 800 MPa at temperatures up to 1200 ЊC and about 200 MPa at 1800 ЊC. The strengths of these alloys under 1000 ЊC are equivalent to or higher than those of the commercially used Ni-base superalloys, MAR-M247 and CMSX-10. The Nb concentration dependence of strength was investigated using a series of Ir-Nb alloys with Nb concentrations from 0 to 25 at. pct. It was found that the Ir-base alloys were strengthened by L1 2 precipitation hardening. The potential of the Ir-base alloys for ultra-high temperature use is discussed.

Based on a fourth generation single crystal (SC) superalloy, TMS-138, we designed new SC alloys that contain higher amount of refractory elements, Nb, Ta, Mo, or Re, for strengthening. The Ru content was also increased to improve the phase stability. The creep strength and microstructure of these alloys were examined and compared with those of the base alloy TMS-138 and a third generation SC superalloy, CMSX-10K. As predicted by our alloy design program, TMS-162 (Mo and Ru addition) and TMS-173 (Re and Ru addition) exhibited excellent creep properties. Their times to 1% creep deformation at 1100 C/137MPa were about 2.5 times as long as that of TMS-138 and 5 times as long as that of CMSX-10K. The temperature capability of TMS-162 has reached a project target of 1100 C under stress at 137MPa and a creep rupture life as long as 1000 h, which is the highest ever reported.

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