Thermal fatigue properties of Sn–x Ag–0˙5Cu (x = 1, 1˙2 and 3, mass%) lead free solder interconnects were discussed from the viewpoints of both morphology and grain boundary character distribution. 3Ag showed the longer thermal fatigue life than 1Ag and 1˙2Ag. Both cracks, which were initiated by thermal strain, and grain boundary damage due to grain boundary sliding degraded the thermal fatigue lives. From a microstructural observation using orientation imaging microscopy, recrystallisation of tin grains was observed, and 3Ag suppressed coarsening of tin grains after further thermal fatigue as compared with 1Ag and 1˙2Ag. Moreover, 3Ag showed a larger amount of coincidence site lattice boundaries than 1Ag and 1˙2Ag. It is suggested that in 3Ag not only smaller tin grains but also larger amount of coincidence site lattice boundaries suppressed crack propagation and grain boundary sliding.
Coagulation factor IX (FIX) is synthesized by hepatocytes, and the lack of this protein causes hemophilia B. Liver nonparenchymal cells, including liver sinusoidal endothelial cells (LSECs) and extrahepatic cells in the body, are scarcely shown to have an ability to synthesize and secrete FIX. The present study investigated the existence of cells responsible for synthesizing FIX other than hepatocytes in mice using gene expression analyses and FIX-specific clotting assays. Among the several organs investigated, including liver, lung, spleen, kidney, brain, intestine, and tongue, FIX mRNA expressions were observed only in the liver. From the liver, hepatocytes and LSECs were isolated. FIX mRNA expression and FIX protein secretion were observed exclusively in the hepatocytes. Furthermore, the clotting activity of FIX secreted from the cultured hepatocytes was found to be dependent on the concentration of vitamin K2. These findings indicated that the hepatocyte is the only cell type that biochemically produces functional FIX in vivo. This highlights the importance of hepatocytes or cells that are fully differentiated toward the hepatic lineage for possible application for regenerative medicine and for targeting gene delivery to establish new cell-based treatments for hemophilia B.
High temperature SiC devices require the materials for packaging also capable of working at higher temperature than those for Si devices. SiC devices are expected to help hybrid vehicle power control units (PCUs) produce higher power in a more compact size as SiC can withstand higher voltages and temperatures (above 300°C) than silicon with less power loss. The improvement of interconnection technologies is increasingly becoming a top priority, particularly for the operation of SiC devices at relatively high temperatures. We propose a new interconnection method using nickel electroplating to replace Al wire bonding or die-bonding using solder materials. During the evaluation of the reliability of interconnections annealed at up to 500°C, we observed no significant changes in mechanical or electrical properties. We found that micro-plating connections can be used successfully for high-temperature-resistant packaging for SiC devices.
Hemophilia A is an X-linked rescessive bleeding disorder that results from F8 gene aberrations. Previously, we established embryonic stem (ES) cells (tet-226aa/N6-Ainv18) that secrete human factor VIII (hFVIII) by introducing the human F8 gene in mouse Ainv18 ES cells. Here, we explored the potential of cell transplantation therapy for hemophilia A using the ES cells. Transplant tet-226aa/N6-Ainv18 ES cells were injected into the spleens of severe combined immunodeficiency (SCID) mice, carbon tetrachloride (CCl 4 )-pretreated wild-type mice, and CCl 4 -pretreated hemophilia A mice. F8 expression was induced by doxycycline in drinking water, and hFVIII-antigen production was assessed in all cell transplantation experiments. Injecting the ES cells into SCID mice resulted in an enhanced expression of the hFVIII antigen; however, teratoma generation was confirmed in the spleen. Transplantation of ES cells into wild-type mice after CCl4-induced liver injury facilitated survival and engraftment of transplanted cells without teratoma formation, resulting in hFVIII production in the plasma. Although CCl 4 was lethal to most hemophilia A mice, therapeutic levels of FVIII activity, as well as the hFVIII antigen, were detected in surviving hemophilia A mice after cell transplantation. Immunolocalization results for hFVIII suggested that transplanted ES cells might be engrafted at the periportal area in the liver. Although the development of a safer induction method for liver regeneration is required, our results suggested the potential for developing an effective ES-cell transplantation therapeutic model for treating hemophilia A in the future.
Abstract Plasminogen activator inhibitor‐1 (PAI‐1) is known as an inhibitor of fibrinolytic system. Previous studies suggest that PAI‐1 is involved in the pathogenesis of osteoporosis induced by ovariectomy, diabetes, and glucocorticoid excess in mice. However, the roles of PAI‐1 in early‐stage osteogenic differentiation have remained unknown. In the current study, we investigated the roles of PAI‐1 in osteoblastic differentiation of mesenchymal stem cells (MSCs) using wild‐type (WT) and PAI‐1‐deficient (PAI‐1 KO) mice. PAI‐1 mRNA levels were increased with time during osteoblastic differentiation of MSCs or mesenchymal ST‐2 cells. However, the increased PAI‐1 levels declined at the mineralization phase in the experiment using MC3T3‐E1 cells. PAI‐1 deficiency significantly blunted the expression of osteogenic gene, such as osterix and alkaline phosphatase enhanced by bone morphogenetic protein (BMP)‐2 in bone marrow‐derived MSCs (BM‐MSCs), adipose‐tissue‐derived MSCs (AD‐MSCs), and bone marrow stromal cells of mice. Moreover, a reduction in endogenous PAI‐1 levels by small interfering RNA significantly suppressed the expression of osteogenic gene in ST‐2 cells. Plasmin did not affect osteoblastic differentiation of AD‐MSCs induced by BMP‐2 with or without PAI‐1 deficiency. PAI‐1 deficiency and a reduction in endogenous PAI‐1 levels did not affect the phosphorylations of receptor‐specific Smads by BMP‐2 and transforming growth factor‐β in AD‐MSCs and ST‐2 cells, respectively. In conclusion, we first showed that PAI‐1 is crucial for the differentiation of MSCs into osteoblasts in mice.
Objective: To investigate the effect of protease-activated receptor 1 (PAR4) deficiency on H1N1 influenza A virus (IAV) infection in mice. PAR4 is the major thrombin-receptor on mouse platelets. In...
