High temperature fatigue characteristics of P/M and hot-forged W-Re and TZM for X-ray target of CT scanner

The fatigue strengths at 1000 °C of layered W-Re/TZM, bulk W-Re and bulk TZM for x-ray target materials were successfully evaluated under load-controlled four-point bending by introducing a fatigue failure criterion as twotimes increase of initial compliance. The obtained fatigue strengths at 1000 °C for layered W-Re/TZM and bulk WRe were similar and 280 MPa and 290 MPa at 106 cycles, respectively, while that of bulk TZM was 200 MPa. During fatigue loading at 1000 °C, dominant fatigue damage would be multiple intergranular crack nucleation and propagation, which would induce the increase of compliance. The reasonability of the fatigue failure criterion was confirmed by the fatigue process observations and the results of room temperature fatigue tests of the specimens tested at 1000 °C up to the cycles corresponding to the fatigue failure criterion

Method of measuring conducted disturbance using both capacitive voltage probe and current probe

1999 International Symposium on Electromagnetic Compatibility, May 17-21, 1999, Surugadai Memorial Hall, Chuo University, Tokyo, Japa

An emerging strategy for cancer treatment targeting aberrant glycogen synthase kinase 3β

金沢大学がん研究所分子標的がん医療研究開発センターImprovement in the outcome of cancer patients who are refractory to currently available treatments relies on the development of target-directed therapies. One group of molecular targets with potential clinical relevance is a set of protein tyrosine kinases encoded mostly by proto-oncogenes and that are frequently deregulated in cancer. Glycogen synthase kinase 3β (GSK3β), a serine/threonine protein kinase, has emerged as a therapeutic target for common chronic diseases including type 2 diabetes mellitus, neurodegenerative disorders, inflammation and osteoporosis. This is based on its currently known functions and primary pathologic causalities. GSK3β has well characterized roles in the regulation of gene transcription and in oncogenic signaling. We have shown that deregulated GSK3β promotes gastrointestinal, pancreatic and liver cancers and glioblastomas. Furthermore, we have demonstrated that inhibition of GSK3β attenuates cancer cells survival and proliferation, induces cell senescence and apoptosis and sensitizes tumor cells to chemotherapeutic agents and ionizing radiation. This has led us to propose GSK3β as a potential therapeutic target in cancer. The anti-tumor effects of GSK3β inhibition are mediated by changes in the expression and phosphorylation of molecules critical to the regulation of cell cycling, proliferation and apoptosis and underlie the pathological role for GSK3β in cancer. Investigation of the mechanisms responsible for deregulation of GSK3β and the consequent downstream pathologic effects in cancer cells has shed light on the molecular pathways leading to tumorigenesis. This will allow exploration of novel therapeutic strategies for cancer that target aberrant GSK3β. © 2009 Bentham Science Publishers Ltd

Detection of active fraction of glycogen synthase kinase 3β in cancer cells by nonradioidotopic in vitro kinase assay

Division of Translational and Clinical Oncolog

Deregulated GSK3β sustains gastrointestinal cancer cells survival by modulating human telomerase reverse transcriptase and telomerase

金沢大学がん研究所分子標的がん医療研究開発センターPurpose: Glycogen synthase kinase-3β (GSK3β) regulates multiple cell signaling pathways and has been implicated in glucose intolerance, neurodegenerative disorders, and inflammation. We investigated the expression, activity, and putative pathologic role of GSK3β in gastrointestinal, pancreatic, and liver cancers. Experimental Design: Colon, stomach, pancreatic, and liver cancer cell lines; nonneoplastic HEK293 cells; and matched pairs of normal and tumor tissues of stomach and colon cancer patients were examined for GSK3β expression and its phosphorylation at serine 9 (inactive form) and tyrosine 216 (active form) by Western immunoblotting and for GSK3β activity by in vitro kinase assay. The effects of small-molecule GSK3β inhibitors and of RNA interference on cell survival, proliferation, and apoptosis were examined in vitro and on human colon cancer cell xenografts in athymic mice. The effects of GSK3β inhibition on human telomerase reverse transcriptase (hTERT) expression and telomerase activity were compared between colon cancer and HEK293 cells. Results: Cancer cell lines and most cancer tissues showed increased GSK3β expression and increased tyrosine 216 phosphorylation and activity but decreased serine 9 phosphorylation compared with HEK293 cells and nonneoplastic tissues. Inhibition of GSK3β resulted in attenuated cell survival and proliferation and increased apoptosis in most cancer cell lines and in HT-29 xenografts in rodents but not in HEK293 cells. GSK3β inhibition in colon cancer cells was associated with decreased hTERT expression and telomerase activity. Conclusion: The results indicate that deregulated GSK3β sustains gastrointestinal cancer cells survival through modulation of hTERT and telomerase. © 2009 American Association for Cancer Research

Brief Measure for Screening Complicated Grief: Reliability and Discriminant Validity

BACKGROUND: Complicated grief, which is often under-recognized and under-treated, can lead to substantial impairment in functioning. The Brief Grief Questionnaire (BGQ) is a 5-item self-report or interview instrument for screening complicated grief. Although investigations with help-seeking samples suggest that the BGQ is valid and reliable, it has not been validated in a broader population. METHODOLOGY/PRINCIPAL FINDINGS: A questionnaire was mailed to a randomly selected sample (n = 5000) residing in one of 4 areas of Japan. The BCQ was examined for responders who were bereaved more than 6 months and less than 10 years (n = 915). Non-specific psychological distress was assessed with the K6 screening scale. Multiple group confirmatory factor analysis supported a uni-dimensional factor structure and the invariance of parameters across gender and age. Cronbach's alpha was sufficiently high (alpha = .75) to confirm internal consistency. Average Variance Extracted (0.39) was higher than the shared covariance (0.14) between BGQ and K6, suggesting discriminant validity. CONCLUSIONS: The results of this study support the reliability and validity of the BGQ in the Japanese population. Future studies should examine predictive validity by using structured interviews or more detailed scales for complicated grief

Municipal health expectancy in Japan: decreased healthy longevity of older people in socioeconomically disadvantaged areas

BACKGROUND: Little is known about small-area variation in healthy longevity of older people and its socioeconomic correlates. This study aimed to estimate health expectancy at 65 years (HE65) at the municipal level in Japan, and to examine its relation to area socio-demographic conditions. METHODS: HE65 of municipalities (N = 3361) across Japan was estimated by a linear regression formula with life expectancy at 65 years and the prevalence of those certificated as needing nursing care. The relation between HE65 and area socio-demographic indicators was examined using correlation coefficients. RESULTS: The estimated HE65 (years) ranged from 13.13 to 17.39 for men and from 14.84 to 20.53 for women. HE65 was significantly positively correlated with the proportion of elderly and per capita income, and negatively correlated with the percentage of households of a single elderly person, divorce rate, and unemployment rate. These relations were stronger in large municipalities (with a population of more than 100,000) than in small and medium-size municipalities. CONCLUSION: A decrease in healthy longevity of older people was associated with a higher percentage of households of a single elderly person and divorce rate, and lower socioeconomic conditions. This study suggests that older people in urban areas are susceptible to socio-demographic factors, and a social support network for older people living in socioeconomically disadvantaged conditions should be encouraged

Effect of Loading Frequency on Fatigue Behavior of Magnesium Alloy in Humid Environment

Effect of loading frequency on fatigue behavior of an extruded AZ61 magnesium alloy was investigated at 50? -80%RH environment. The frequencies applied were 1 and 10 Hz. It was found that at stresses below the fatigue limit (at 20? -55%RH), the fatigue fracture was time dependent where fatigue lives for both frequencies were almost identical. In contrast, the fatigue fracture in the region higher than the fatigue limit was dominated by the number of loading cycles. Fatigue fracture at low stress amplitudes for both frequencies were originated from the corrosion pit formed on the surface. Effect of frequency on fatigue crack growth behavior was also investigated. The results showed that in the near-threshold region, the 1 Hz frequency demonstrated higher fatigue crack growth resistance compared to the 10 Hz

End-Crosslinking Gelation of Poly(amide acid) Gels studied with Scanning Microscopic Light Scattering

Network formation in the gelation process of end-crosslinked poly(amide acid) gels, which are the precursor of end-crosslinked polyimide gels, was studied by scanning dynamic light scattering. The gelation process is essentially non-reversible due to the formation of covalent bonds. The molecular structure formed in the gelation process is controlled by varying the equivalence ratio of end-crosslinker to oligomer during the preparation. It was found that a couple of relaxation modes are observed in the gelation point even for semi-rigid poly(amide acid) solutions. This is similar to flexible polymer solutions and convenient to characterize the molecular structure in the gelation processes. The fast mode is related to the cooperative diffusion process of the network structure formed by over lapped macromolecules, i.e., gel mode, which determines the averaged mesh-size of the network structure. The slow mode is related to the relaxation time of the formation of the transient network structure, which shows a slowing down close to the gelation point and disappears after gelation due to the formation of the permanent network structure

Nonlinear spatiotemporal evolution of whistler mode chorus waves in Earth's inner magnetosphere

We analyze the nonlinear evolution of whistler mode chorus waves propagating along a magnetic field line from their equatorial source. We solve wave evolution equations off the equator for the wave magnetic field amplitude and wave frequency, subject to boundary conditions at the equator comprising model "chorus equations" that describe the generation of a seed chorus element. The electron distribution function is assumed to evolve adiabatically along a field line. The wave profiles exhibit nonlinear convective growth followed by saturation. Convective growth is due to nonlinear wave trapping, and the saturation process is partly due to a combination of adiabatic effects and a decreasing resonant current with latitude. Notwithstanding computationally expensive full-scale kinetic simulations, our study appears to be the first to analyze the nonlinear evolution and saturation of whistler mode waves off the equator