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Friction welding of aluminum alloys to copper was carried out in order to examine the weldability with particular reference to the effect of the intermetallic formation at the weld interface. The maximum joint efficiencies of A1050, 5000 and 6000 series alloys to copper were more than 80 %, while those of 2000 series and A7075 alloys joints were less than 50 % and scattered widely. For joints of A2024 and 5000 series alloys which contain rather high magnesium content, intermetallic compounds of Al-Cu-Mg system were formed at the weld interface in addition to that of Al-Cu system. In the other joints, only intermetallic compounds of Al-Cu system were formed. A mixing layer, in which pieces of copper and intermetallic compounds were incorporated into aluminum alloy, was formed near the weld interface. The mixing was very intense, in the joints with low efficiency, namely joints of A2011, A2024 and A7075 to copper, and these joints were fractured in this mixing layer and at the weld interface. On the other hand, the joints with high efficiency, namely joints of A5052 and A6061 to copper, had thin and even mixing layer. The mixing layers observed in the joints of A1050, A2017, A5056 and A6063 to copper were thinner than those of the other joints.

Friction welding of 6061 aluminum alloy was carried out in order to examine the relationship among deformation heat input at the upset stage, upset burn-off length and joint performance. The joint performance was evaluated by tensile testing and fatigue testing. Stabilized tensile strength was obtained when the deformation heat input at the upset stage and the upset burn-off length exceeded 200J/s and 4mm, respectively. Weld condition at the weld interface and the width of softened area affected fatigue strength more than tensile strength. That is, when the weld condition at the weld interface is good and the softened area is wide, fatigue strength increases because the stress disperses in the softened area. On the other hand, when the weld condition at the weld interface is good and the softened area is narrow, and when the weld condition at the weld interface is somewhat poor in spite of the wide softened area, fatigue strength decreases because the stress concentrates at the weld interface. The fatigue limit obtained by the fatigue testing reveals that, when the deformation heat input at the upset stage and the upset burn-off length exceed a certain value, sound joints can be produced.

Friction welding of S15CK carbon steel was carried out in order to examine the relationship between heat input for welding and joint strength. The joint strength is evaluated from tensile strength. The heat input is a heat source for welding solid materials and was classified into 6 inputs: friction heat input, deformation heat input and total heat input in the friction stage and upset stage.The most important heat input for evaluating the joint strength among these heat inputs was experimentally investigated through the tensile strength of joints welded under various welding conditions.As a result, it was made clear that the deformation heat input in the upset stage is much strongly related with the joint strength, and sound weld joints can be obtained deformation heat inputs more than about 100J/s. Moreover, it was recognized that the joint strength is possible to evaluate by the upset loss, therefore, sound welded joints can be obtained with about 1.2 mm upset burn-off length or more also.

TPS4590 Background: Only 5%-15% of patients (pts) with advanced bladder cancer attain long-term survival with standard first-line cisplatin-based chemotherapy. Programmed death 1 (PD-1)/PD-L1 inhibitors have proven effective in recurrent, advanced urothelial cancer. Emerging data suggest these agents may also be useful in the first-line setting. In KEYNOTE-052, first-line pembro, an anti–PD-1 antibody, demonstrated antitumor activity and acceptable safety in cisplatin-ineligible pts with advanced urothelial cancer. KEYNOTE-361 (NCT02853305) is a randomized, open-label, phase 3 study of pembro with or without chemotherapy versus chemotherapy alone in pts with advanced urothelial carcinoma. Methods: Key eligibility criteria include age ≥18 years; histologically or cytologically confirmed unresectable/metastatic urothelial carcinoma of the renal pelvis, ureter, bladder, or urethra; measurable disease (RECIST v1.1, investigator review); no prior systemic chemotherapy ([neo]adjuvant platinum-based chemotherapy with recurrence > 12 months after completion is allowed); ECOG PS 0-2; and provision of a tumor sample for biomarker analyses. Pts will be randomly assigned 1:1:1 to receive pembro 200 mg every 3 weeks (Q3W), pembro + investigator’s choice of chemotherapy (gemcitabine [1000 mg/m2 on day 1 and 8 Q3W] + cisplatin [70 mg/m2 Q3W]), or chemotherapy alone. Cisplatin-ineligible pts randomly assigned to chemotherapy will receive gemcitabine + carboplatin [AUC 5 Q3W]. Chemotherapy choice must be selected before randomization. Treatment will continue until progressive disease, unacceptable adverse events (AEs), or 35 cycles of pembro (pembro arms only). Response will be assessed Q9W for the first year and Q12W thereafter. AEs will be evaluated throughout and graded per NCI CTCAE v4.0. Primary end points are progression-free survival (RECIST v1.1 per central review) and overall survival; secondary end points include objective response rate and safety and tolerability. Efficacy outcomes will be compared for pembro vs chemotherapy and pembro + chemotherapy vs chemotherapy. Enrollment is ongoing; ~990 pts will be enrolled. Clinical trial information: NCT02853305.

Purpose: Enzalutamide (ENZ) is a potent androgen receptor (AR) antagonist with activity in castration-resistant prostate cancer (CRPC); however, progression to ENZ-resistant (ENZ-R) CRPC frequently occurs with rising serum PSA levels, implicating AR full-length (ARFL) or variants (AR-Vs) in disease progression. Experimental Design: To define functional roles of ARFL and AR-Vs in ENZ-R CRPC, we designed 3 antisense oligonucleotides (ASO) targeting exon-1, intron-1, and exon-8 in AR pre-mRNA to knockdown ARFL alone or with AR-Vs, and examined their effects in three CRPC cell lines and patient-derived xenografts. Results: ENZ-R-LNCaP cells express high levels of both ARFL and AR-V7 compared with CRPC-LNCaP; in particular, ARFL levels were approximately 12-fold higher than AR-V7. Both ARFL and AR-V7 are highly expressed in the nuclear fractions of ENZ-R-LNCaP cells even in the absence of exogenous androgens. In ENZ-R-LNCaP cells, knockdown of ARFL alone, or ARFL plus AR-Vs, similarly induced apoptosis, suppressed cell growth and AR-regulated gene expression, and delayed tumor growth in vivo. In 22Rv1 cells that are inherently ENZ-resistant, knockdown of both ARFL and AR-Vs more potently suppressed cell growth, AR transcriptional activity, and AR-regulated gene expression than knockdown of ARFL alone. Exon-1 AR-ASO also inhibited tumor growth of LTL-313BR patient-derived CRPC xenografts. Conclusions: These data identify the AR as an important driver of ENZ resistance, and while the contributions of ARFL and AR-Vs can vary across cell systems, ARFL is the key driver in the ENZ-R LNCaP model. AR targeting strategies against both ARFL and AR-Vs is a rational approach for AR-dependent CRPC. Clin Cancer Res; 21(7); 1675–87. ©2015 AACR.

N -Acetylglucosaminyl(GlcNAc) sulfotransferase, which transfers sulfate from adenosine 3′-phosphate 5′-phosphosulfate to GlcNAc at the nonreducing end of oligosaccharides, was purified 887-fold with a 8.4% yield from 2-day-old chick corneas by chromatography on CM-Sepharose, WGA-agarose, GlcNAc-agarose, and 3′,5′-ADP-agarose columns. The purified enzyme has an optimum pH of 6.0 (Mes buffer) and specifically transfers a sulfate to GlcNAc at the nonreducing end but not to internal GlcNAc. The enzyme was stimulated by protamine and Mn 2+ . SDS–polyacrylamide gel electrophoresis of the purified enzyme still showed two main bands (66 and 55 kDa) with some minor bands. It appears that this enzyme competes with β-galactosyltransferase in binding to the nonreducing GlcNAc residue on KS synthesis; this suggests that the sulfation of the GlcNAc residue is coupled with the elongation of the KS chain.

Two rice (Oryza sativa) waxy mutations of the Japonica background were shown to contain approximately 20% of the fully spliced mRNA relative to the wild type. Sequencing analysis of the entire waxy genes of the two mutants revealed the presence of premature translation termination codons in exon 2 and exon 7. These results indicated that the lower accumulation of fully spliced RNA in the mutants was caused by nonsense-mediated decay (NMD), which is an RNA surveillance system universally found in eukaryotes. It is interesting that levels of RNA retaining intron 1 were not changed by premature nonsense codons, suggesting that splicing may be linked with NMD in plants, as previously found in mammalian cells. Measurements of the half-lives of waxy RNAs in transfected rice protoplasts indicated that the half-life of waxy RNA with a premature nonsense codon was 3.3 times shorter than that without a premature nonsense codon. Because the wild-type waxytranscripts, which are derived from the Wxbgene predominantly distributed among Japonica rice, have been shown to be less efficiently spliced and their alternative splicing has been documented, we examined whether these splicing properties influenced the efficiency of NMD. However, no effects were observed. These results established that NMD occurs in rice waxy RNA containing a premature nonsense codon.

Carbon steel was friction welded and torsion fatigue tests were conducted on weld joints having an upset burr in order to reveal the effect of an upset burr on fatigue strength. It was found that the fatigue strength of joints having a constant toe radius decreased with a decrease in hardness ratio (hardness of toe/hardness of base material). Softened joints (hardness ratio≤1) and hardened joints (hardness ratio>1) fractured at the toe of the upset burr and in the base material, respectively. On the other hand, the fatigue strength of joints having constant hardness ratio increased with toe radius. Using correlation analysis, a reasonable multiple regression equation was obtained between torsional fatigue strength and the fatigue factors, that is, the hardness ratio and toe radius of the upset burr. Thus, using this regression equation, the torsional fatigue strength of friction welded joints having an upset burr could be estimated.

Valproic acid (VPA) is widely used to treat various types of epilepsy. Interindividual variability in VPA pharmacokinetics may arise from genetic polymorphisms of VPA-metabolizing enzymes. This study aimed to examine the relationships between plasma VPA concentrations and the -161CT single nucleotide polymorphism in uridine diphosphate glucuronosyltransferase (UGT) 2B7 genes in pediatric epilepsy patients.This study included 78 pediatric epilepsy patients carrying the cytochrome P450 (CYP) 2C9*1/*1 genotype and who were not treated with the enzyme inducers (phenytoin, phenobarbital, and carbamazepine), lamotrigine, and/or topiramate. CYP2C9*3 and UGT2B7 -161CT polymorphisms were identified using methods based on polymerase chain reaction-restriction fragment length polymorphism. Blood samples were drawn from each patient under steady-state conditions, and plasma VPA concentrations were measured.Significant differences in adjusted plasma VPA concentrations were observed between carriers of CC, CT, and TT genotypes in the UGT2B7 -161CT polymorphism (P = 0.039). Patients with the CC genotype had lower adjusted plasma VPA concentrations than those with CT or TT genotype (P = 0.028).These data suggest that the UGT2B7 -161CT polymorphism in pediatric epilepsy patients carrying the CYP2C9*1/*1 genotype affects VPA concentration.

Summary Valproic acid, which is widely used to treat various types of epilepsy, may cause severe hyperammonemia. However, the mechanism responsible for this side effect is not readily apparent. Polymorphisms in the genes encoding carbamoyl-phosphate synthase 1 (CPS1) and N -acetylglutamate synthase (NAGS) were recently reported to be risk factors for the development of hyperammonemia during valproic acid-based therapy. This study aimed to examine the influence of patient characteristics, including polymorphisms in CPS1 4217C>A and NAGS -3064C>A, on the development of hyperammonemia in Japanese pediatric epilepsy patients. The study included 177 pediatric epilepsy patients. The presence of a 4217C>A polymorphism in CPS1 was determined using an allele-specific polymerase chain reaction (PCR)-based method, and the presence of a -3064C>A polymorphism in NAGS was determined using a PCR-based restriction fragment length polymorphism method. Hyperammonemia was defined as a plasma ammonia level exceeding 200μg/dL. We observed a significant difference between the combination of valproic acid with phenytoin and the development of hyperammonemia in both univariate and multivariate analyses. With regard to the CPS1 4217C>A polymorphism, we did not observe a significant association with the development of hyperammonemia. In conclusion, CPS1 4217C>A polymorphism may not be associated with the development of hyperammonemia in Japanese population.

Friction welding of 6061 aluminum alloy similar material was carried out in order to examine a relationship between heat input and joint performance. The joint performance is evaluated by tensile test. The heat input is a heat source for welding solid materials and is classified into six inputs, that is, friction heat input and deformation heat input during friction stage, upset stage and total stage respectively. The most important heat input for evaluating the joint performance among these heat inputs was experimentally investigated through the tensile strength of joints welded with many welding conditions because the friction welding mechanism is so complexed. As the results, the deformation heat input during upset stage was much related with the joint performance, and sound welded joints were obtained with 200 J/s or more deformation heat input. Moreover, it was recognized that the deformation heat input during upset stage was in proportion to the upset loss, therefore, sound welded joints were obtained with 3 mm or over upset loss also.

非イオン性造影剤iomeprolのhigh performance membrane (HPM) dialyzerを用いた血液透析による除去をin vitroおよび臨床例で検討した. In vitro (QB200ml/min, QD500ml/min, 4h) での透析による除去率はメルトラフラックス150 (MF150: CDA): 99.9%, KF20C (EVAL): 99.7%, BK1.6F (PMMA): 99.2%と各dialyzer間で差は認められなかったが, 透析膜への吸着率ではMF150: 16.7%, KF15C: 35.7%, BK1.6F: 49.4%とBK1.6Fで高い吸着率を示した. 臨床例での除去率はメルトラフラックス110 (MF110: CDA): 81.8%, 73.7%, MF150: 89.4%, KF20C: 84.5%, BK1.6F: 80.5%, 77.3%, FB210U (CTA): 84.8%, FB210U (HDF施行): 89.9%といずれのdialyzerにおいても効率良く除去された. Iomeprolは問題となる副作用もなく透析により効率良く除去されるため腎機能の廃絶した慢性透析患者にも安全に使用できると思われた.

Treatment of Cp*TaCl4 with 1 equiv of Li2(R2-dad) in THF afforded Cp*Ta(R2-dad)Cl2 (R = iPr (1), tBu (2)). The chlorido ligands of 1 and 2 reacted smoothly with 2 equiv of LiC⋮CtBu, MeMgI and LiStB...

Film-shaped thermoelectric materials have been prepared for thermoelectric modules for cooling or electricity generation. Flash evaporation and casting are adopted for preparing film-shaped p-, n-type (Bi,Sb)2(Te,Se)3 materials. The chemical characteristics and the thermoelectric properties of these samples have been investigated. By controlling the preparation temperature or selecting the impurities, film-shaped thermoelectric materials, comparable in properties with bulk-shaped sintered materials, are obtained. The thermoelectric power factor of the n-type (6–7 μm) film sample, prepared by the flash evaporation method, is 30 μW cm−1K2. In addition, that of the p-type (0.5–0.7 μm) film sample , prepared by the casting method with added impurities, is 40 μW cm−1K2.

Friction welding of 6061 aluminum alloy to steels was conducted, the effects of welding conditions and various heat treatments of the welded joint on the joint strength were examined. Under the same welding conditions, the tensile strength of A6061/steeI joints were much alike for all the steels used. Tensile strength was seen to increase when the upset pressure was raised. In the case of joints welded at upset pressure not less than 80MPa, tensile fracture occurred in thermal softened A6061 area and the tensile fracture surface approached closer to the weld interface according to increases in the upset pressure, because softened A6061 was exhausted with burr under the action of upset pressure. It was concluded that joint strength depends on the width of the softened A6061 area. The whole A6061 area of T62 heat treated joint hardened to the same extent as the received material of A6061-T6, and tensile strength of this joint was high compared with that of the weld joint.

To investigate if detection of copy number aberrations of chromosomes 3, 7, 9p21, and 17 using multicolour fluorescence in situ hybridization (FISH) predicts patient outcome in non-muscle-invasive bladder cancer (NMIBC).In all, 118 bladder wash samples were prospectively collected from patients who underwent transurethral resection of bladder tumour (median age 50.5 years, male/female: 91/27, tumour grade 1/2/3: 18/52/42, stage pTis/Ta/T1: 8/62/42) from 2007 to 2010. The 118 samples were analysed using the UroVysion® kit to detect the copy numbers of chromosomes 3, 7, 9p21, and 17. The variant fraction (VF; the sum of the non-modal copy number fraction of each chromosome) was defined as abnormal when the percentage was ≥16%. The percentage deletion of 9p21 (fraction of null or one copy number of the 9p21 locus) was defined as abnormal when the percentage was ≥12%. Maffezzini risk criteria were also analysed in our cohorts.There was recurrence in 57 (48.3%) patients and disease progression in 12 (10.1%), with a median follow-up of 35.7 months. Multivariate analysis showed that the percentage 9p21 loss (12%) was an independent prognostic factor for recurrence (P0.001, odds ratio [OR] 3.24, 95% confidence interval [CI] 1.85-5.62). For disease progression, tumour grade, positive urine cytology, concurrent carcinoma in situ, and a mean VF of16% were significant prognostic factors in univariate analysis. In multivariate analysis, a mean VF of16% was a prognostic factor for disease progression (P = 0.048, OR 6.07, 95% CI 1.02-57.45).Multicolour-FISH analysis using a commercially available kit could be a powerful tool not only for diagnosis, but also for prognostication in patients with NMIBC.

in different cancer types. We previously found that miR-125b directly targets p53, Bak1 and Puma, and promoted prostatic tumor growth in both intact and castrated mice. In this study, we further underline the clinical importance of miR-125b by detecting miR-125b levels in prostate cancer (CaP) specimens. In addition, we conducted animal experiments to determine whether miR-125b has potential as a therapeutic target for treatment of CaP. METHODS: For detection of miR-125b expression, total RNA was isolated from cancer cell-enriched, fresh-frozen CaP tissues, as well as fresh-frozen BPH specimens, using TRIzol reagent. The miR125b level was measured using qPCR. Animal experiments were performed according to the protocols approved by the Animal Care and Use Committee at UCD, CA USA. Male nude mice implanted with testosterone pellets were inoculated s.c with CWR22 CaP cell suspensions and then treated with polyethylenimines (PEI)-complexed antimiR-125b (PEI-anti-miR-125b) or PEI-anti-miR-125b plus Taxol. PEI can form complexes with miRNA, increase internalization and facilitate miRNA release into cytoplasm. RESULTS: 133 prostate specimens (46 BPHs and 87 CaPs) were analyzed for their expression of miR-125b. The average miR125b level was 3.0-fold greater in CaPs than in BPHs. In 42 CaPs having Gleason score available, the miR-125 levels correlate with Gleason scores (103 18 relative fold in Gleason score 5-6 vs 160 16 in Gleason score 7-10, p 0.03), suggesting that miR-125b contributes to pathological progression of CaP. In animal studies, mice were treated with PEI-anti-miR-125b (10 g/day, thrice a week for 4 weeks) or PEI-anti-miRNA control, and significant tumor-inhibitory effects was observed in anti-miR-125b treatment group compared to control group. In addition, mice bearing CWR22 tumors were treated with PEI-antimiR-125b plus Paclitaxel (20 mg/kg/week for 4 weeks). It was found that anti-miR-125b significantly increased the therapeutic efficiency of Taxol. CONCLUSIONS: Data from qPCR provide evidence that dysregulation of miR-125b is common in CaP patients and the levels of miR-125b are correlated with pathological progression of CaP. Additionally, results from animal studies show that anti-miR-125b inhibited growth of CWR22 tumors and sensitized CaP cells to Taxol, suggesting that miR-125b can be used as a target for improved CaP treatment.

Destructive test of the joints was carried out for examining the impact and fatigue strength. The softened area of A6061 side of the joints welded under a higher upset pressure is narrower compared with that welded under a lower upset pressure, because the softened area of A6061 side was expelled as the upset burr by the action of upset pressure. The dynamic strength of the joints depends on the width of the softened area of A6061 side. In the case of smoothed impact specimen, the impact absorbed energy of the joints increases with increase in upset pressure, while it decreases with the upset pressure over 240 MPa. On the other hand, no smoothed specimens of A6061 base material fracture. In the case of notched specimen, the impact absorbed energy of the joints welded under the upset pressures over 160 MPa remains to be almost equal to the maximum value, and the maximum joint efficiency is about 15%. The impact fracture occurres both in the mixed area of the weld interface and in the softened A6061 area. The fatigue strength at a given endurance (number of cycles to failure 107) of A6061 base material and the joints welded under 120 MPa and 240 MPa upset pressure are 121 MPa, 112 MPa and 122 MPa, respectively. The fatigue fracture of the joints occurres in the softened A6061 area or in the mixed area of the weld interface and the softened A6061 area depending on the welding conditions.

Combined trimodality therapy, including transurethral resection and platinum-based chemoradiotherapy, has shown promising results for muscle-invasive bladder cancer. However, this type of treatment may decrease survival as a result of delayed cystectomy in patients with non-responding tumors. DNA repair proteins may affect survival of bladder cancer patients receiving combined trimodality therapy, by affecting the perioperative nature of the tumor cells or by repairing DNA damaged by platinum agents and radiation. We investigated the associations of excision repair cross-complementing group 1 (ERCC1), X-ray repair cross-complementing group 1 (XRCC1) and apurinic/apyrimidinic endonuclease 1 (APE1) expression with response and survival in 157 locally advanced bladder cancer patients receiving combined trimodality therapy, in order to determine the predictive value of the expression of these proteins in patient selection for therapy. We examined ERCC1, XRCC1 and APE1 expression in tumor specimens using immunohistochemistry. Patients positive for ERCC1, positive for XRCC1 and positive for either ERCC1 or XRCC1, exhibited significantly improved disease-specific survival rates (P=0.023, 0.025 and 0.0091, respectively). In multivariate analysis, combined ERCC1 and XRCC1 expression was independently associated with disease-specific mortality [risk ratio (RR): 0.64; 95% confidence interval (CI), 0.43-0.94 and P=0.024]. Thus, combined ERCC1 and XRCC1 expression may serve as an independent prognostic marker for survival in bladder cancer patients receiving combined trimodality therapy. Prospective studies with a larger sample size are required to confirm these results.

542 Background: Chronic kidney disease (CKD) is a risk factor for the cardiovascular disease, which affect to the patients’ survival, while an EORTC randomized control trial did not show superiority of partial nephrectomy (PN) against localized renal cell carcinoma (RCC) in overall survival compared to radical nephrectomy (RN). We aimed to evaluate the role of operative methods affecting the survival and tried to estimate a predictive model for high risk CKD after surgery. Methods: We reviewed the data of 357 cases with clinical T1 RCC treated by RN (292 cases, RN group) or PN (65 cases, PN group) at Yamaguchi University Hospital or its related hospitals. We supposed the cases with CKD stage 3b or higher after surgery as high risk CKD. And we set the primary endpoints as the ratio of the cases with high risk CKD and overall survival after surgery. Results: Median follow-up period after surgery was 70 months (3-161). Statistically significant difference in performance status and clinical T stage were observed between the groups, but not in other patients’ characteristics. Mean values of preoperative eGFR were 69.2 and 65.5 ml/min/1.73m2 in RN and PN group, which decreased to 46.0 and 57.9 at 5 years after surgery, respectively. There was a significant difference in the incidence of high risk CKD between RN (39.3%) and PN group (2.2%) at 5 years after surgery. During follow up period, 17 cases (4.4%) were inducted to dialysis, there was no difference in the incidence between the RN and PN group. Multivariate analysis showed that eGFR ( < 72 ml/min/1.73m2; Odds ratio 15.3), proteinuria (Odds ratio 3.84), smoking (Odds ratio 2.76), BMI ( > 23; Odds ratio 2.66) and age ( > 67 years old; Odds ratio 2.47) could be significant predictive factors for high risk CKD at 5years after surgery. Our predicting model for high risk CKD showed 86.8% of sensitivity and 74.8% of specificity. But there was no significant difference in overall survival between the RN and PN group. Conclusions: Although there was a significant difference in the incidence of high risk CKD between RN and PN group, operative methods did not affect to the survival. Postoperative high risk CKD could be predictable by preoperative clinical factors.

We investigated whether centrosome amplification (CA) obtained from bladder washing cytology (BWC) specimens may be a useful prognostic biomarker for patients with non-muscle invasive bladder cancer (NMIBC). The study cohort included 78 patients with pathologically confirmed NMIBC. BWC specimens were obtained from all patients during transurethral resection of bladder tumor (TURBT), and CA was evaluated by immunofluorescence staining using a pericentrin polyclonal antibody. A positive case of CA was defined as a specimen in which >5% of cells contained ≥3 centrosomes per cell. CA was detected in 26.9% (21 of 78) of BWC specimens obtained from NMIBC patients. Disease progression was observed in 11.5% (9 of 78) of patients, with a median follow-up of 32 months. In univariate analyses, CA obtained from BWC specimens, initial or recurrent, and washing cytology were significantly associated with progression-free survival ( P = 0.009, 0.02, and 0.03, respectively). Multivariate Cox model analyses revealed that CA was the most significant prognostic factor for disease progression (hazard ratio: 2.22, 95% confidence interval: 1.13–4.90, P = 0.022). These data suggest that analysis of CA using bladder washing cytological specimens may provide crucial predictive information regarding disease progression in NMIBC.

High strength aluminum alloy A7075 was friction welded under three forging pressures, while other friction welding conditions were kept constant throughout the welding cycle. Friction welded joints were offered to destructive test for evaluating the bending and torsional strength. The maximum joint efficiencies were 80.2, 98.4 and 104.8% in bending test, torsion test with smoothed specimen and that with notched specimen, respectively. In bending test and torsion test with notched specimen fracture occurred at the transition layer between the interfacial layer and the deformed zone of welded joints, while it occurred in softened zone near the transition zone in torsion test with smoothed specimen.

Friction welding of a 6061 aluminum alloy to a S45C carbon steel was carried out using the insert metal of a 1050 aluminum. Optimum thickness of the insert metal, friction pressure, forge pressure, friction time and rotational speed of welding conditions were determined as 4mm, 90MPa, 300MPa, 1.2s and 2250rpm, respectively. When the insert metal turned into a thin (20-30μm) and homogeneous layer at the weld interface, the maximum joint efficiency of tensile strength was obtained and was about 95%. Successful welds were obtained by taking each optimum welding condition even if the thickness of the insert metal was varied from 2 to 6mm.

This study was designed to identify clinical risk factors for adverse effects of antituberculous therapy and their frequency.A retrospective study of cohorts was undertaken from April 2004 to March 2007. We analyzed the clinical records of 861 patients with tuberculosis treated at Higashi Nagoya Hospital. The factors that were associated with adverse effects in univariate analysis (P0.1) were then subjected to multivariate Cox regression analysis for calculation of the hazard ratios (HRs) and their 95% confidence intervals (95% CIs).Suspension of antituberculous therapy was necessary because of adverse effects in 247 patients (28.7%). The chief adverse effects leading to discontinuation of treatment were liver dysfunction (12.9%), skin rash (6.7%), and gastrointestinal dysfunction (4.1%), while other effects accounted for less than 5.0% of discontinuations. Risk factors for liver dysfunction according to Cox proportional hazards analysis were HCV infection (HR 2.86; 95% CI 1.59 to 5.15; p0.001); hepatocellular damage at admission (HR 2.06; 95% CI 1.25 to 3.39; p = 0.005) and high-dose isoniazid (increase per mg/kg: HR 1.36; 95% CI 1.18 to 1.56; p0.001). Collagen disease was a risk factor for skin rash (HR 6.06; 95% CI 2.81 to 13.05; p0.001). Risk factors for gastrointestinal dysfunction were a high body mass index (increase per kg/m2: HR 0.80; 95% CI 0.71 to 0.91; p0.001) and advanced age (increase per year: HR 1.03; 95% CI 1.01 to 1.06; p 0.018).Adverse effects may lead to substantial additional medical costs because of the need for more medications and tests, as well as a longer hospital stay. Identification of the risk factors for adverse effects of antituberculous therapy should help to minimize such events in tuberculosis patients.

Genetic polymorphism of cytochrome P450 2C9 (CYP2C9) and cytochrome P450 2C19 (CYP2C19) is widely known to contribute to interindividual differences in the pharmacokinetics of some antiepileptic drugs. We developed a rapid detection assay of polymorphisms of CYP2C9 and CYP2C19, using the Light Cycler(®) polymerase chain reaction (PCR) system. Using this assay, we examined polymorphisms in 20 Japanese pediatric patients prescribed phenytoin for the treatment of epilepsy, and classified their polymorphisms into four groups: group I, CYP2C9*1/*1 and CYP2C19*1/*1; group II, CYP2C9*1/*1 and CYP2C19*1/*2 or *1/*3; group III, CYP2C9*1/*1 and CYP2C19*2/*2; and group IV, CYP2C9*1/*3 and CYP2C19*1/*2 or *1/*3. The mean maximal elimination rates (V(max)) in groups I, II, III and IV were 13.1, 11.2, 10.2 and 8.0 mg/day/kg, respectively, with statistically significant differences among groups (p=0.012, Kruskal-Wallis analysis). The intrinsic metabolic activity (V(max)/K(m)) of groups I, II, III and IV were 2.9, 2.2, 1.5 and 1.1 l/day/kg, respectively (p=0.009), again with significant differences among groups. These findings indicate that polymorphism of CYP2C9 and CYP2C19 plays an important role in phenytoin metabolism in children. With a total processing time for this assay of less than 3 hours, prediction of the optimal phenytoin dosage based on the CYP2C9 and CYP2C19 genotypes will be possible before commencement of therapy, resulting in the prevention of phenytoin overdoses in pediatric patients with epilepsy.

Objective: We aimed to evaluate the Epstein criteria and the eligibility criteria for active surveillance in the Prostate Cancer Research International study by using immunohistochemical staining. Methods: We reviewed the clinicopathological data of 119 patients who underwent prostate biopsy, with prostate-specific antigen levels being � 4 ng/ml. The data of patients with detected prostate cancer were compared with those of patients with clinically significant prostate cancer. To discriminate insignificant prostate cancer, immunohistochemical staining for Ki67, p53, bcl-2, BUBR1, PTEN and E-cadherin was performed. Results: Ki67, BUBR1 and E-cadherin staining showed significant correlation with the Gleason score. Ki67 and BUBR1 staining showed significant correlations with the Epstein criteria, and Ki67, BUBR1 and E-cadherin staining correlated with the Gleason score and Prostate Cancer Research International criteria. The sensitivity and specificity of Ki67 or BUBR1 staining in discriminating the prostate cancer cases classified as clinically insignificant according to the Epstein criteria were 62.5 and 84.2%, or 57.1 and 100%, respectively. The sensitivity and specificity of Ki67, BUBR1 or E-cadherin staining in discriminating prostate cancer cases classified as clinically insignificant according to the Prostate Cancer Research International criteria were 75 and 87.5%, 66.7 and 100% or 50 and 100%, respectively. The predictive accuracy of Ki67 and BUBR1 staining was equivalently high in relation to both sets of criteria (77.6 and 83.3%, respectively). Conclusions: These data could provide pathological evidence to support the suitability of the Epstein and Prostate Cancer Research International criteria. Ki67 and BUBR1 may be potential markers in selecting candidates for active surveillance.

This study has been conducted to obtain more improved high manganese steel than A-T and B-T which were investigated in the previous paper.Then, tensile and impact properties at cryogenic temperature of three kinds of high manganese steel, AS (17Mn-12Cr-4.5Si), BV (21Mn-6.3Cr-3.4Si-0.19N) and CT (25Mn-6.5Cr-4.5Si), and their electron beam welded joints were examined by using tensile and instrumented Charpy impact testing apparatus.From the view points of ultimate tensile strength, elongation and total absorbed energy at cryogenic temperature, CT is far better than A-T and B-T, and can be considered as an improved high manganese steel.

There are few reliable markers to distinguish tumors with aggressive characteristics from others at the time of initial diagnosis in non-muscle-invasive bladder cancer. The purpose of this study was to identify a genomic marker that allows the prediction of prognosis for non-muscle-invasive bladder cancers. We screened the genome-wide copy number in 41 patients with non-muscle-invasive urothelial carcinoma of the bladder by array-based comparative genomic hybridization using arrays spotted with 4,030 bacterial artificial chromosome clones. A loss of 8p23.3 (clone 923) was correlated significantly with a higher histological grade (P = 0.0026) and advanced pathological stage (P = 0.0148). Both recurrence-free and progression-free survival rates were lower in patients with tumors without 8p23.3, compared with those with 8p23.3 (P = 0.0146 and 0.0473, respectively; log-rank test). These data suggest that the loss of 8p23.3 is a novel genomic marker allowing estimation of biological characteristics of non-muscle-invasive bladder cancer.

Fe-Si-O thin films were prepared by Ionized Cluster Beam method, and the effect of oxygen content and heat treatment on their thermoelectric properties and microstructure were examined. As-deposited films were in amorphous state and they showed semiconducting properties with low Seebeck coefficients depending on the amount of oxygen in the temperature range from R. T. to 400°C. Above 450°C, migration of atoms, change of chemical bonds, and growth of microcrystals proceeded remarkably. As a result, the conductivity of the samples with a small amount of oxygen showed some enhancement and that of the samples with a large amount of oxygen showed a remarkable decrease. It is elucidated that the changes of conductivity is dependent on the amount of Si-O amorphous insulator; whether or not the conduction paths between Fe-Si microcrystals were separated by Si-O amorphous insulator caused the different conduction mechanism.

Tensile and shearing tests were carried out on four kinds of explosively clad steels in order to examine these strength and ductility at various test temperatures. Four kinds of explosively clad steels are C1100/SUS304, SUS304/SM41B, SUS316/SM41B and TP28/SM41B.Results obtained are as follows.(1) Strength of the explosively clad steel, C1100/SUS304, at 700 K is obviously small compared to strength at 293 K. It has excellent strength and ductility at 4.2 K.(2) Strength and ductility of the explosively clad steels, SUS304/SM41B and SUS316/SM41B at 700 K are sufficient. When the temperature becomes to 4.2 K, these strength is reduced and ductility decreases rapidly.(3) The explosively clad steel, TP28/SM41B, has a high tensile strength at 700 K or 4.2 K and has a low shearing strength at same temperature.

This paper reports the effect of neutron irradiation on strength of high manganese steel which is a candidate for nuclear fusion reactor components. Cryogenic temperature strengths of two kinds of high manganese steel, A-T (18Mn-6.8Cr-4.7Si) and B-T (22Mn-6.4Cr-4.4Si-0.18N), and their electron beam welded joints were investigated under various irradiated conditions.Results obtained are summarized as follows.(1) At cryogenic temperature, high manganese steel A-T exhibited a faint serration, B-T showed a clear serration.(2) Ultimate tensile strength and 0.2% proof stress of base metal and electron beam welded joint of A-T and B-T increased with increasing of neutron fluence.(3) Elongation of base metal and electron beam welded joint of A-T and B-T decreased with increasing of neutron fluence.

The incidence of prostate cancer and the resultant mortality rates in Japanese men are lower compared with the rates for Caucasians; however, the Gleason score at diagnosis is higher in Japanese men compared with Caucasians. Loss of 13q is one of the most common chromosomal alterations in prostate cancer. To elucidate the difference in the rate of loss of 13q between Japanese and Caucasian men, we examined the allelic imbalance (AI) on chromosome 13q in 32 Japanese and 39 German prostate cancer patients with a fluorescent polymerase chain reaction technique using 12 microsatellite markers. Benign and malignant histology was identified by a single pathologist and laser capture microdissection was used to gather cancer cells. Although there were no statistical differences in patient background characteristics, the frequency of AI at 13q14 (D13S1253) and at 13q21 (D13S166) was significantly higher in Japanese patients compared with German patients (p = 0.0128 and p = 0.0078, respectively). The frequency of AI at 13q14 was significantly higher in tumors with high Gleason scores (GS) compared with tumors with low GS (p = 0.0478). The present observations suggest that the frequency of genetic alterations at 13q14 may underlie differences in the biological behavior of prostate cancer between Japanese and Caucasian populations.

Human breast milk samples collected in 2007–2008 from four countries, Vietnam (Hanoi), China (Beijing), Korea (Seoul) and Japan (Sendai, Kyoto and Takayama), were analyzed for persistent organic pollutants (POPs) such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane-related compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Comparing with previous surveys, the present study indicates that the DDTs in breast milk from China and Vietnam had gradually decreased during the last decade, but were still 5–10 times higher than those in other nations. The ratios of p,p′-DDE/p,p′-DDT and o,p′-DDT/p,p′-DDT were higher in Beijing than in the other countries, suggesting that there is less fresh intake of commercial DDT products and a possible exposure to dicofol in China. CHL and PCB levels were relatively higher in mothers from Japan, whereas β-HCH and HCB were more common in Chinese women. In Japan, it is suspected that mothers in the urban/coastal area (Sendai) were more continuously exposed to organochlorine pesticides (OCPs) than mothers in the rural/inland area (Takayama). In addition, OCP levels in primiparae were significantly higher than those in multiparae from Japan and Korea. These indicate that both parity and regional factors are major determinants of the levels of OCPs and PCBs in human milk. On the other hand, higher concentrations of PBDEs were observed in mothers' milk from Korea. The congener was dominated by BDE-47 (43–54%), followed by BDE-153 (23–33%) in all regions except for Beijing where BDE-28 (23%) was relatively abundant. In Japanese breast milk, regional and parity-dependent distributions were not observed for PBDEs. Among PBDE congeners, age-dependency was observed for BDE-153, which was negatively correlated (p

In this work, thermal conductivities of gas diffusion layer (GDL) under controlled temperature, humidity and stress are measured. Additionally, we investigated the anisotropic thermal conductivity of GDLs. The experimental results showed that thermal conductivity of in-plane direction was much higher than that of trough-plane direction for all the samples that were measured. This result indicated thermal conductivity of GDLs to be strongly anisotropic since GDL is a highly porous material which contains large amount of air inside the GDL. Moreover, we found that thermal conductivity of GDL in the through-plane direction increased as the compression on the GDL was increased.