Application of EQ bond coat to EB-PVD TBC systems

To prevent the formation of SRZ in the log-time high-temperature exposure of the turbine blades, thermodynamically equilibrium phase such as gamma-prime phase of the substrate is use as an oxidation-resistant bond coat. The previous study clarified that this EQ coating shows excellent interface stability and it does not degrade mechanical strength due to the SRZ formation. In this study, TBC life test of EB-PVD ceramics coated EQ coating is investigated with other conventional MCrAlY coatings. The 4th and 5th generation superalloys are used for substrates. About 150 μm thick of EQ coating, conventional NiCoCrAlY and CoNiCrAlY coating are deposited by LPPS and HVOF on the substrates. After polishing the surface of deposited bond coat, specimens are pre-oxidized in the EB-PVD chamber in 0.2 Pa of oxygen partial pressure. 150 μm thick of YSZ is deposited by EB-PVD on the pre-oxidized bond coat, following the pre-oxidation. Samples are heat treated cyclically in an electric furnace at 1135 °C with 1 h cycles. Fast cooling rate is obtained by air blow with each cooling cycle. As a result, it is found that TBC life of LPPS EQ-coated TMS-138A showed over twice of other conventional bond coats. Interrupted and failed samples are observed by SEM and EPMA. The differences of bond coats and its deposition processes in the microstructure, TGO growth and TBC life are discussed. On the other hand, oxidation characteristics of YSZ-TBC and EQ bond coated substrate using burner rig developed by NIMS are discussed. And also the recycling of TBC with EQ bond coat is discussed

ICONE 17 -75179 Heat Transfer Experiments of Mini-Tube Bank

ABSTRACT Heat transfer and flow behavior in the mini rod bank were examined. The tubes are simulated with a 1 mm diameter nickel wire. The tube bank was composed of the 5×5 square-lattice array and the 5×5 staggered array. The tube banks were arranged in the flow channel of 30 mm wide or 15 mm wide, 15 mm high and 480 mm long. Water was used as the test fluid. A flow rate was varied in the range of the Reynolds number Re = uD/ν of 1 ~ 800, where D is the tube diameter. The approaching velocity of fluid in the channel was in the range of 0.0036 m/s ~ 0.68 m/s. Experiments were performed at atmospheric pressure. The measured heat transfer coefficients of the rows after the second row were lower than those of the first row and the difference between those increased as the Reynolds number was increased. The difference turned to decrease around Reynolds number = 50 in the 15 mm wide test section experiments of the square -lattice array and around Reynolds number = 200 in the 30 mm wide test section experiments of the staggered array. The heat transfer coefficients reached back to the first row value around Re = 400 in the former experiments. It was confirmed through the present results and the previous results that the heat transfer in the rear rows is deteriorated by the flow stagnation in the wake region of the preceding rod and the deterioration is recovered as the Reynolds number is increased since the wake region becomes disturbed

Functional Lateralization of Speech Processing in Adults and Children Who Stutter

Developmental stuttering is a speech disorder in fluency characterized by repetitions, prolongations, and silent blocks, especially in the initial parts of utterances. Although their symptoms are motor related, people who stutter show abnormal patterns of cerebral hemispheric dominance in both anterior and posterior language areas. It is unknown whether the abnormal functional lateralization in the posterior language area starts during childhood or emerges as a consequence of many years of stuttering. In order to address this issue, we measured the lateralization of hemodynamic responses in the auditory cortex during auditory speech processing in adults and children who stutter, including preschoolers, with near-infrared spectroscopy. We used the analysis–resynthesis technique to prepare two types of stimuli: (i) a phonemic contrast embedded in Japanese spoken words (/itta/ vs. /itte/) and (ii) a prosodic contrast (/itta/ vs. /itta?/). In the baseline blocks, only /itta/ tokens were presented. In phonemic contrast blocks, /itta/ and /itte/ tokens were presented pseudo-randomly, and /itta/ and /itta?/ tokens in prosodic contrast blocks. In adults and children who do not stutter, there was a clear left-hemispheric advantage for the phonemic contrast compared to the prosodic contrast. Adults and children who stutter, however, showed no significant difference between the two stimulus conditions. A subject-by-subject analysis revealed that not a single subject who stutters showed a left advantage in the phonemic contrast over the prosodic contrast condition. These results indicate that the functional lateralization for auditory speech processing is in disarray among those who stutter, even at preschool age. These results shed light on the neural pathophysiology of developmental stuttering

Dense methylation of types 1 and 2 regulatory regions of the CD10 gene promoter in infant acute lymphoblastic leukemia with MLL/AF4 fusion gene

金沢大学医薬保健研究域Infant acute lymphoblastic leukemia (ALL) displays distinct biologic and clinical features with a poor prognosis. The CD10-negative immunophenotype of infant ALL is a hallmark and provides a predictable signature of mixed-lineage leukemia (MLL) rearrangement. Although CD10 negativity reflects an earlier stage of B-cell development, complete IgH gene rearrangements (VDJH), found in almost half of the patients, show more mature IgH status. Discordance between immunophenotype and genotype of infant ALL suggests an aberrant process in immunophenotypic steps of differentiation or a secondary down-regulation of CD10 expression. In this study, CD10-negative infant ALL with MLL/AF4, CD10-positive infant ALL with germline MLL, CD10-positive pre-B ALL cell line, infant acute myeloid leukemia (AML; M5) with MLL/AF9 and pediatric AML (M2) with AML1/ETO were analyzed for VDJH status and methylation of CD10 gene promoters. Three of the 4 infant ALL samples showed complete rearrangements of the VDJH gene with productive joints. Bisulfite sequencing of CD10 type 1 and 2 promoters showed that more than 84% of the cytosine-phosphate-guanine (CpG) dinucleotides identified were methylated in all 3 CD10-negative infant ALL samples with MLL/AF4. The CpG dinucleotides distributed in the clusters of putative Sp1-binding sites and functionally active regulatory regions of the promoters were fully methylated. In contrast, none of the CpG dinucleotides were methylated in the CD10-positive ALL samples. Structural evidence of dense methylation in the CD10 gene promoter suggested that methylated transcription factor binding sites contribute to CD10 silencing as an epigenetic mechanism. © 2010 by Lippincott Williams & Wilkins

Modeling of the inherence of feedback regulation and stem cell behavior in granulopoiesis

金沢大学医学部附属病院小児科Long-standing controversies in hematopoiesis are the mechanisms of self-maintenance and differentiation commitment of the hematopoietic stem cells (HSC), and regulation of the peripheral control of hematopoiesis. In the present study, we have applied a threedimensional cellular automaton (CA) model to granulopoiesis in order to identify the internally generative theoretical relationship between microscopic mechanisms and macroscopic behavior of hematopoietic processes. The number of mitotic event of the cells in a proliferating phase, the transit time of each of 15 differential stages from HSC to mature cells (designated as Tl to Tl 5, and Tdup for HSC duplication time), and the neighborhood rules for HSC self-renewal were incorporated in this model system as analytical parameters. Homeostatic granulopoiesis was achieved when the following inequalities for the transit times were fulfilled: Tl > Z Tn (n = 2 to 15) and Tdup > 1/2 Tl. Importantly, stabilization of the cell production was induced in a negative feedback manner following external perturbation of the peripheral granulocyte numbers. The Tdup of individual HSC was dramatically fluctuated to produce the offspring responding to this perturbation. A single cell kinetic analysis demonstrated that symmetrical or asymmetrical cell division of the HSC was recruited in a transitional manner resulting in generation of the regulatory effect on the lineage-commitment processes. The inherence of feedback regulation would be a characteristic feature of the emergent dynamical property in the hematopoietic system. The CA modeling will provide the framework to analyze the behavior of HSC and to understand abnormal kinetics of the cells such as minimal residual disease in the treatment of leukemias

Walking and Sports Participation and Mortality From Coronary Heart Disease and Stroke

ObjectivesWe aimed to examine the impact of exercise on mortality from cardiovascular disease (CVD) in Asian populations.BackgroundFew data have been available in Asian countries, where job-related physical activity is higher than that in Western countries.MethodsBetween 1988 and 1990, 31,023 men and 42,242 women in Japan, ages 40 to 79 years with no history of stroke, coronary heart disease (CHD), or cancer, completed a self-administered questionnaire. Systematic mortality surveillance was performed through 1999, and 1,946 cardiovascular deaths were identified. We chose the second lowest categories of walking and sports participation as the reference to reduce a potential effect of ill health.ResultsMen and women who reported having physical activity in the highest category (i.e., walking ≥1 h/day or doing sports ≥5 h/week) had a 20% to 60% lower age-adjusted risk of mortality from CVD, compared with those in the second lowest physical activity category (i.e., walking 0.5 h/day, or sports participation for 1 to 2 h/week). Adjustment for known risk factors, exclusion of individuals who died within two years of baseline inquiry, or gender-specific analysis did not substantially alter these associations. The multivariate-adjusted hazard ratios (95% confidence interval) for the highest versus the second lowest categories of walking or sports participation were 0.71 (0.54 to 0.94) and 0.80 (0.48 to 1.31), respectively, for ischemic stroke (IS); 0.84 (0.64 to 1.09) and 0.51 (0.32 to 0.82), respectively, for CHD; and 0.84 (0.75 to 0.95) and 0.73 (0.60 to 0.90), respectively, for CVD.ConclusionsPhysical activity through walking and sports participation might reduce the risk of mortality from IS and CHD

Aplastic anemia successfully treated with rituximab: The possible role of aplastic anemia-associated autoantibodies as a marker for response

金沢大学医薬保健研究域医学系A 1-yr-old Japanese male infant developed hepatitis-associated aplastic anemia (AA), and anti-thymocyte globulin (ATG) plus cyclosporine A (CsA) was administered without any appreciable effects. Laboratory examination of the patient\u27s serum obtained before therapy revealed various autoantibodies, such as PA-IgG, anti-platelets, anti-single-stranded DNA (ssDNA), and anti-double-stranded DNA (dsDNA) antibodies (Abs) in addition to anti-DRS-1 Abs and anti-moesin Abs, both of which are known to be detectable in approximately 40% of all patients presenting with AA. He was therefore treated with 17.5mg/kg/d rituximab 5.5months after ATG/CsA therapy. The same rituximab therapy was repeated three times once a month thereafter. His neutrophil counts started to increase 50d after the first rituximab therapy and he achieved a complete remission at 16months after the last rituximab administration. All of the autoantibodies including anti-ssDNA, dsDNA, DRS-1, and moesin became undetectable when he attained the remission. Anti-CD20 monoclonal antibody therapy may be effective in a subset of patients with AA characterized by the presence of autoantibodies. © 2011 John Wiley & Sons A/S

Hedgehog Promotes Neovascularization in Pancreatic Cancers by Regulating Ang-1 and IGF-1 Expression in Bone-Marrow Derived Pro-Angiogenic Cells

http://creativecommons.org/licenses/by/2.0/ PublisherBackground: The hedgehog (Hh) pathway has been implicated in the pathogenesis of cancer including pancreatic ductal adenocarcinoma (PDAC). Recent studies have suggested that the oncogenic function of Hh in PDAC involves signaling in the stromal cells rather than cell autonomous effects on the tumor cells. However, the origin and nature of the stromal cell type(s) that are responsive to Hh signaling remained unknown. Since Hh signaling plays a crucial role during embryonic and postnatal vasculogenesis, we speculated that Hh ligand may act on tumor vasculature specifically focusing on bone marrow (BM)-derived cells. Methodology/Principal Findings: Cyclopamine was utilized to inhibit the Hh pathway in human PDAC cell lines and their xenografts. BM transplants, co-culture systems of tumor cells and BM-derived pro-angiogenic cells (BMPCs) were employed to assess the role of tumor-derived Hh in regulating the BM compartment and the contribution of BM-derived cells to angiogenesis in PDAC. Cyclopamine administration attenuated Hh signaling in the stroma rather than in the cancer cells as reflected by decreased expression of full length Gli2 protein and Gli1 mRNA specifically in the compartment. Cyclopamine inhibited the growth of PDAC xenografts in association with regression of the tumor vasculature and reduced homing of BM-derived cells to the tumor. Host-derived Ang-1 and IGF-1 mRNA levels were downregulated by cyclopamine in the tumor xenografts. In vitro co-culture and matrigel plug assays demonstrated that PDAC cell-derived Shh induced Ang-1 and IGF-1 production in BMPCs, resulting in their enhanced migration and capillary morphogenesis activity. Conclusions/Significance: We identified the BMPCs as alternative stromal targets of Hh-ligand in PDAC suggesting that the tumor vasculature is an attractive therapeutic target of Hh blockade. Our data is consistent with the emerging concept that BM-derived cells make important contributions to epithelial tumorigenesis

A Proteomic Approach for the Diagnosis of ‘Oketsu’ (blood stasis), a Pathophysiologic Concept of Japanese Traditional (Kampo) Medicine

‘Oketsu’ is a pathophysiologic concept in Japanese traditional (Kampo) medicine, primarily denoting blood stasis/stagnant syndrome. Here we have explored plasma protein biomarkers and/or diagnostic algorithms for ‘Oketsu’. Sixteen rheumatoid arthritis (RA) patients were treated with keishibukuryogan (KBG), a representative Kampo medicine for improving ‘Oketsu’. Plasma samples were diagnosed as either having an ‘Oketsu’ (n = 19) or ‘non-Oketsu’ (n = 29) state according to Terasawa's ‘Oketsu’ scoring system. Protein profiles were obtained by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) and hierarchical clustering and decision tree analyses were performed. KBG treatment for 4 or 12 weeks decreased the ‘Oketsu’ scores significantly. SELDI protein profiles gave 266 protein peaks, whose expression was significantly different between the ‘Oketsu’ and ‘non-Oketsu’ states. Hierarchical clustering gave three major clusters (I, II, III). The majority (68.4%) of ‘Oketsu’ samples were clustered into one cluster as the principal component of cluster I. The remaining ‘Oketsu’ profiles constituted a minor component of cluster II and were all derived from patients cured of the ‘Oketsu’ state at 12 weeks. Construction of the decision tree addressed the possibility of developing a diagnostic algorithm for ‘Oketsu’. A reduction in measurement/pre-processing conditions (from 55 to 16) gave a similar outcome in the clustering and decision tree analyses. The present study suggests that the pathophysiologic concept of Kampo medicine ‘Oketsu’ has a physical basis in terms of the profile of blood proteins. It may be possible to establish a set of objective criteria for diagnosing ‘Oketsu’ using a combination of proteomic and bioinformatics-based classification methods