Stress concentration in adhesively bonded joints, which is considered a major factor affecting their strength, can be avoided by tailoring the material properties of the adhesives using a ...functionally graded adhesive (FGA). The material properties of second-generation acrylic (SGA) adhesives can be simply changed by changing the mixing ratio of the agents. However, the superiority of FGA joints using SGA adhesives has not been experimentally clarified yet. Therefore, in this study, a shear strength test and a constant load low-cycle shear test were conducted on single lap joint (SLJ) specimens tailoring the adhesive layer stepwise. The FGA specimen was compared with the non-tailored specimens using stiff or flexible adhesives. The SLJ test results showed 16% improvement in the joint strength by stepwise tailoring of the adhesive layer. Additionally, the difference in the strain distributions among the different adhesive layers was investigated via a digital image correlation (DIC) method, and the shear strain at the edge of the FGA specimen was more than 40% decreased compared to the non-tailored specimen using the flexible adhesive. The low-cycle test results also showed the superiority of the FGA specimen to the other specimens. The FGA specimen held up more than 4 times the number of cycle of other specimens with an applied load of 18 kN or more. This was attributed to the suppressed plastic deformation at the edges of the adhesive layer owing to the introduction of FGAs.
X-linked lymphoproliferative syndrome type 2 is a rare hereditary immunodeficiency caused by mutations in the XIAP gene. This immunodeficiency frequently results in hemophagocytic ...lymphohistiocytosis, although hypogammaglobulinemia and dysgammaglobulinemia are also common.
We identified 17 patients from 12 Japanese families with mutations in XIAP. The Glu349del mutation was observed in 3 patients, each from a different family. Interestingly, these patients exhibited dysgammaglobulinemia but not hemophagocytic lymphohistiocytosis. We conducted an immunological study of patients carrying Glu349del and other mutations to elucidate the pathogenic mechanisms of dysgammaglobulinemia in patients with mutations in the XIAP gene.
We performed an immunological study of 2 patients carrying the Glu349del mutation and 8 patients with other mutations.
Flow cytometry showed that the percentage of memory B cells in patients with a mutation in XIAP was lower than that observed in the healthy controls. The patients with the Glu349del mutation had a lower percentage of memory B cells than those with other mutations. Ig production was reduced in patients with the Glu349del mutation. Increased susceptibility to apoptosis was observed in the patients with other mutations. Susceptibility to apoptosis was normal in patients with Glu349del. Microarray analysis indicated that expression of Ig-related genes was reduced in patients with the Glu349del mutation and that the pattern was different from that observed in the healthy controls or patients with other mutations in XIAP.
Patients carrying the Glu349del mutation in the XIAP gene may have a clinically and immunologically distinct phenotype from patients with other XIAP mutations. The Glu349del mutation may be associated with dysgammaglobulinemia.
Abstract We investigated using the mice role of nitric oxide synthase (NOS) in the spinal dorsal horn in herpetic and postherpetic pain, especially allodynia, which was induced by transdermal ...inoculation of the hind paw with herpes simplex virus type-1 (HSV-1). The virus inoculation induced NOS2 expression in the lumbar dorsal horn of mice with herpetic allodynia, but not postherpetic allodynia. There were no substantial alternations in the expression level of NOS1 at the herpetic and postherpetic stages. Herpetic allodynia was significantly inhibited by i.p. administration of the selective NOS2 inhibitor S-methylisothiourea, but not the selective NOS1 inhibitor 7-nitroindazole. NOS2 expression was observed around HSV-1 antigen-immunoreactive cells. On the other hand, postherpetic allodynia was significantly inhibited by i.p. administration of 7-nitroindazole, but not S-methylisothiourea. The activity of reduced nicotinamide adenine dinucleotide phosphate diaphorase, an index of NOS1 activity, significantly increased in the laminae I and II of the lumbar dorsal horn of mice with postherpetic allodynia, but not mice without postherpetic allodynia. The expression level of NOS1 mRNA in the dorsal root ganglia was similar between mice with and without postherpetic allodynia. The results suggest that herpetic and postherpetic allodynia is mediated by nitric oxide in the dorsal horn and that NOS2 and NOS1 are responsible for herpetic and postherpetic allodynia, respectively. It may be worth testing the effects of NOS2 and NOS1 inhibitors on herpetic pain and postherpetic neuralgia in human subjects, respectively.
Osteoblasts are affected by TNF-α overproduction by immune cells during inflammation. We demonstrate that apoptosis is induced in murine osteoblastic MC3T3-E1 cells by exceeding the concentrations ...100 units/mL of TNF-α and 10 μmol/L of synthetic ceramide. The apoptotic signaling pathway activated by TNF-α was examined in MC3T3-E1 cells. Endogenous cellular ceramide concentrations increased within 3 min, and comparable peak levels were observed for 30 min after TNF-α treatment. Activation of nuclear factor-κB (NF-κB) was detected after TNF-α or synthetic ceramide stimulation. The concentration of NF-κB increased in the perinuclear region after 5 min of treatment and translocation into the nucleus was observed within 15 min of treatment. Degradation of IκBα/MAD-3 was observed after 60 min of ceramide treatment. These results indicate that nuclear translocation and activation of NF-κB through TNF-α generated ceramide may be one important apoptotic signaling pathway in MC3T3-E1 cells. The osteoblastic apoptosis triggered by TNF-α-generated ceramide may explain the inhibition of bone formation during severe bone inflammation.
The divacancies in SiC are a family of paramagnetic defects that show promise for quantum communication technologies due to their long-lived electron spin coherence and their optical addressability ...at near-telecom wavelengths. Nonetheless, a high-fidelity spin-photon interface, which is a crucial prerequisite for such technologies, has not yet been demonstrated. Here, we demonstrate that such an interface exists in isolated divacancies in epitaxial films of 3C-SiC and 4H-SiC. Our data show that divacancies in 4H-SiC have minimal undesirable spin mixing, and that the optical linewidths in our current sample are already similar to those of recent remote entanglement demonstrations in other systems. Moreover, we find that 3C-SiC divacancies have a millisecond Hahn-echo spin coherence time, which is among the longest measured in a naturally isotopic solid. The presence of defects with these properties in a commercial semiconductor that can be heteroepitaxially grown as a thin film on Si shows promise for future quantum networks based on SiC defects.
OBJECTIVE To clarify the mechanism of thrombin receptor mediated signal transduction and the induction of cytokines by thrombin stimulation in rheumatoid synovial fibroblasts. METHODS Cytokines were ...measured by enzyme linked immunosorbent assay (ELISA) in the supernatants of cultured rheumatoid synovial fibroblasts stimulated by thrombin. To assess the mechanism of thrombin receptor mediated signal transduction in the rheumatoid synovial fibroblasts, electrophoretic mobility gel shift assay (EMSA), immunoglobulin κ-chloramphenicol acetyltransferase (CAT) assay, and immunostaining for NF-κB subunit molecule was performed. RESULTS Thrombin stimulation activated the inducible transcription factor NF-κB, and then induced subsequent expressions of interleukin 6 (IL6) and granulocyte colony stimulating factor (G-CSF) in the cells. CONCLUSION Thrombin receptor mediated signal transduction could induce the expressions of IL6 and G-CSF, and increase inflammatory events in the cavum articulare via NF-κB activation.
Nociceptin (orphanin FQ) may act on primary afferents and be involved in the regulation of nociceptive processing. We have shown, using reverse transcription-polymerase chain reaction (RT-PCR), that ...carrageenan-produced peripheral inflammation induces the expression of prepronociceptin (PPN) mRNA in the dorsal root ganglia (DRG). The present experiments were conducted to determine the localization of PPN mRNA in primary sensory neurons after peripheral inflammation, using in situ hybridization. An intraplantar injection of carrageenan induced the expression of PPN mRNA in small and medium sized neurons in the DRG; the effect peaked 0.5 h after carrageenan and subsided by 6 h. All neurons positive for PPN mRNA were positive for vanilloid receptor subtype 1 (VR1)-like immunoreactivity and some VR1-immunoreactive neurons were negative for PPN mRNA. The results suggest that peripheral inflammation induces the production of nociceptin in a sub-population of VR1-positive primary sensory neurons and support the idea that nociceptin produced there is involved in the regulation of nociceptive processing.
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