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Background Methotrexate (MTX) is the anchor drug for treatment of rheumatoid arthritis (RA), but tolerance to MTX is substantially different across ethnics and few studies have assessed efficacy and safety of rapid dose escalation regimen of MTX in Japanese patients with early RA. Objectives To evaluate outcomes of rapid dose escalation regimen of MTX compared with conventional treatment. Methods We implemented a randomized, controlled trial that enrolled patients with RA who fulfilled all of the following criteria: 20 to 70 years-old, disease duration ≤2 years, SDAI ≥11, and without prior use of MTX, tacrolimus (TAC) or biologics. Patients were randomized into rapid escalation (RE) group or conventional treatment (CT) group at 1:1 ratio. In RE group, doses of MTX were escalated up to 0.25 mg/kg/wk within 8 wks after start of MTX and increased maximum tolerable dose or 16 mg/wk until wk 12. If a patient achieved SDAI remission at wk 12, MTX was continued at the same dose. If a patient did not achieve SDAI remission at wk 12 or showed intolerance to MTX, use of TAC or TNF inhibitor (TNFi) were allowed. In CT group, patients were treated with either MTX, TAC, salazosulfapyridine, or bucillamine by the discretion of physicians until wk 12. If a patient achieved SDAI remission at wk 12, same treatment was continued. If a patient did not achieve remission at wk 12, use of TNFi was allowed. Patients were treated by the discretion of physicians at wk 24 and onward. We set two primary endpoints; the percentage of patients achieving SDAI remission and Boolean remission at wk 24. We planned to enroll 120 patients per arm based on expected SDAI remission rates at wk 24, alpha and beta errors and dropout rates. Results Enrollment was terminated prematurely and all patients were followed for 48 wks. Of 115 enrolled patients, 57 were randomly assigned to RE group and 58 to CT group. Baseline demographics were similar between the two groups. The median baseline values (RE vs. CT) were 24.9 and 25.9 for SDAI, 0.88 and 0.69 for HAQ, and 0.64 and 0.61 for EQ-5D, respectively. At wk 24, the percentages of patients achieving remission in RE and CT groups were 42% and 28% by SDAI criteria (p=0.1, χ2 test), and 35% and 17% (p=0.03, χ2 test) by Boolean criteria, respectively. Median values of HAQ at wk 24 in RE and CT groups were 0 and 0.13 (p=0.096, M-W U test), and those of EQ-5D were 0.78 and 0.77 (p=0.12, M-W U test), respectively. At wk 48, these values were not statistically different between the two groups. There were no significant differences between the two groups with incidence of severe adverse events. Conclusions The rapid dose escalation regimen of MTX provided significantly superior Boolean remission rate and tended to provide superior SDAI remission than conventional treatment in patients with early RA in the short term. Disclosure of Interest M. Tsutsumino Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., and Teijin Pharma Ltd., R. Sakai Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Teijin Pharma Ltd., and Bristol-Meyers Squibb., M. Kihara: None declared, K. Amano Grant/research support from: Pfizer Japan Inc., R. Yoshimi Grant/research support from: Bristol-Myers K.K., M. Inoo: None declared, H. Dobashi: None declared, T. Sugihara Grant/research support from: Takeda Pharmaceutical Co. Ltd., Mitsubishi-Tanabe Pharma Co., Chugai Pharmaceutical Co., Ltd., Janssen Pharmaceutical K.K, Santen Pharmaceutical Co., Ltd., Astellas Pharma Inc., Bristol Myers Squibb K.K., Abbvie Japan Co., Ltd., Takeda Pharmaceutical Co., Ltd, and Astellas Pharma Inc., T. Hidaka: None declared, H. Kohsaka Grant/research support from: Ayumi Pharmaceutical Co., Pfizer Japan Inc., Mitsubishi-Tanabe Pharma Corp., Takeda Pharmaceutical Co. Ltd., AbbVie Japan Co. Ltd., Eisai Co., Ltd., Chugai Pharmaceutical Co. Ltd., Bristol-Meyers Squibb, Astellas Pharma Inc., UCB Japan, N. Miyasaka: None declared, M. Harigai Grant/research support from: Ayumi Pharmaceutical Co., Chugai Pharmaceutical Co., Ltd., Eisai Co., Ltd., Nippon Kayaku Co., Ltd., Taisho Toyama Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Mitsubishi Tanabe Pharma Co., Teijin Pharma Ltd., Eisai, Pfizer Japan Inc., Sanofi-Aventis KK., Santen Pharmaceutical Co., Ltd and Sekisui Medical Co., Ltd.

This study was carried out to examine the changes in plasma concentrations of the Ca-binding antimicrobial proteins S100A7 and S100A8 during pregnancy in dairy cows. Holstein Friesian cows (n = 19) were inseminated with Holstein Friesian semen. Blood was collected at days 30, 60, 90, 120, 150, 180, 210, 240 and 270 after insemination. Plasma was used for measuring the concentrations of S100A7 and S100A8. Both S100A7 and S100A8 concentrations showed similar patterns during gestation; they increased during the midgestation, between days 90 and 180, and then declined before calving. The findings indicated that plasma concentrations of S100A7 and S100A8 did not change significantly during pregnancy in cows. Further studies are required to determine the roles of S100A7 and S100A8 in physiological function during pregnancy in dairy cows.

Existing mechanical relays have reliability-related issues including unstable contact resistance and limited cycle life. These problems are caused by mechanical fatigue and wearing of the contact surfaces. In the liquid metal micro switch (LiMMS), we employ a liquid-liquid contact to address these issues. The switching operation is achieved by forming a gap in the liquid metal using gas expansion. Our prototype has a microchannel on a glass substrate to hold a tiny amount of mercury, 0.15 mm in width and 0.1 mm in height, and TaN thin-film heaters on a ceramic substrate to expand the operating gas by heating. The substrates are bonded together and the total size of the device is 5/spl times/5/spl times/1.4 mm. We successfully demonstrated 70-m/spl Omega/ on-resistance, 1 ms-switching speed, the ability to handle up to 1 A of dc current and over 1/spl times/10/sup 8/ cycle operation. LiMMS also has good RF performance, better than 1 dB insertion loss, and better than 20 dB isolation up to 18 GHz.

The microstructural evolution of melt-spun Sm8Fe88−xCo4Zrx (x=0, 2, 3.5 at%) ribbons obtained at a wheel speed about 75 m/s has been investigated by means of three-dimensional atom probe (3DAP) and transmission electron microscopy (TEM). As-quenched, heat treated and nitrogenated samples mainly consist of SmFe7 phase and α-Fe, with a small amount of Sm2Fe17 phase. In the Zr-free samples, grain sizes were approximately 20 nm for α-Fe and 100 nm for SmFe7 in the as-quenched state, and were 100 nm for α-Fe and 500 nm for SmFe7 in the annealed samples. After nitrogenation, grain refinement was noticed, but the average grain size was still over 100 nm. As-quenched alloy containing 3.5 at% Zr composed mainly of amorphous phase, which reveals that the Zr addition improved the glass forming ability. An ultra-fine (∼20 nm) equiaxed nanocomposite (α-Fe/SmFe7 or α-Fe/SmFe7Nx) microstructure was obtained in the annealed and nitrogenated Zr-containing alloys. The Zr addition was effective in refining the grain size due to the enrichment of Zr atoms at the interfaces between α-Fe and SmFe7 phases, the optimum hard magnetic properties (with coercivity Hc∼8.92 kOe, remanence Br∼8.27 kG and (BH)max∼11.81 MGOe) were obtained in the nitrided powder after the Zr addition.

Influence of deposition parameters on the deposition rate and the mechanical properties of diamond like carbon (DLC) films deposited by plasma based ion implantation and deposition (PBII) using combined radio frequency (RF) and negative high voltage pulses has been investigated. The hardness and deposition rate for the typical deposition condition is higher for the acetylene (C2H2) plasma than for the methane (CH4) plasma. Unlike a pulsed glow discharge process, the deposition rate can be controlled by both the average input RF power and the process pressure. The DLC films show relatively low compressive stress (0.35 GPa) at the high process pressure (2 Pa), but the stress increases at the low process pressure region (

We reported the results of the endovascular treatment using Guglielmi detachable coil (GDC) for wide-necked aneurysms. Fourteen aneurysms were treated with remodeling technique. One aneurysm was performed endovascular treatment followed by partial neck clipping. The other was treated with scaffolding technique. All aneurysms could not be performed by conventional GDC treatment initially because of coil protrusion into the parent artery due to wide neck of these aneurysms. These aneurysms sited at anterior circulation system in 10 cases, and at posterior circulation system in 6 cases. Immediately after the procedure, the obliteration rate could be obtained complete occlusion in 3 cases, > 95% occlusion in 7 cases, > 90% occlusion in 3 cases and < 90% occlusion in 3 cases. In 14 patients follow-up angiography or magnetic resonance image (MRI) was carried out. The angiographic follow-up period is range from 2 to 19 months (mean: 10 months). The results of angiographical follow-up indicated increasing obliteration rate with all aneurysms except for 2 cases. In these 2 cases, the reembolization was needed for recanalization of the aneurysm. The clinical follow-up period is range form one to 26 months (mean: 15 months). There is no evidence of aneurysmal rupture and all cases have been survival without any permanent neurological deficits. The GDC treatment with additional technique (remodeling technique, combined neck-clipping and coiling therapy, scaffolding technique) provides safety and effectiveness, even if there are wide-necked aneurysms.

Background Sustained clinical remission is crucial in the treatment of rheumatoid arthritis (RA). However, baseline predicting factors to achieve sustained clinical remission in RA patients treated with abatacept (ABT) are little known. Objectives The ABROAD (ABbatacept Research Outcomes as a first-line biological Agent in the real worlD) study is the prospective multicenter observational cohort study, in which 44 institutions in the west side of Japan participate to investigate both efficacy and safety of ABT in biologic-naive RA patients. The purpose of the present study was to determine the useful markers associated with sustained clinical remission by the intravenous ABT infusion treatment in different age groups (age ≥65 vs Methods Two-hundred and seventy-seven RA patients with high or moderate disease activity (female =84.8%, mean age at the ABT initiation =63.2 years old, disease duration =7.9 years) were enrolled. Disease Activity Score 28 joint based on C- reactive protein (DAS28-CRP) remission rate at 24, 36, and 48 weeks after the initiation of ABT treatment were examined. Then, patient profiles, disease activity, concomitant drug use, and laboratory findings at baseline associated with sustained clinical remission (>12 weeks) during the last 24 weeks in the whole treatment period (48 weeks) were determined by logistic regression analysis. Results The proportion of patients, who achieved DAS28-CRP-defined clinical remission at 24 and 48 weeks, were 35.1% and 36.5% in elderly patients (≥65 years old) and 34.9% and 43.4% in younger patients ( Conclusions The efficacy of ABT in biologic-naive RA patients was equivalent between younger and elderly patient groups, while the baseline clinical characteristics in association with clinical remission were totally different. ACPA positivity or MDA at baseline in elderly, but concomitant MTX use or lower HAQ score at baseline in younger patients, may be the useful predicting factors for achieving sustained clinical remission by ABT. Disclosure of Interest M. Sekiguchi Grant/research support from: Bristol-Myers K.K., T. Fujii Grant/research support from: Bristol-Myers K.K., M. Kitano Grant/research support from: Bristol-Myers K.K., K. Matsui Grant/research support from: Bristol-Myers K.K., H. Hashimoto: None declared, A. Yokota: None declared, K. Miki: None declared, A. Yamamoto Grant/research support from: Bristol-Myers K.K., T. Fujimoto: None declared, T. Hidaka: None declared, N. Shimmyo: None declared, K. Maeda: None declared, T. Kuroiwa: None declared, I. Yoshii: None declared, K. Murakami Grant/research support from: Bristol-Myers K.K., K. Ohmura Grant/research support from: Bristol-Myers K.K., S. Morita: None declared, Y. Kawahito Grant/research support from: Bristol-Myers K.K., N. Nishimoto: None declared, T. Mimori Grant/research support from: Bristol-Myers K.K., H. Sano Grant/research support from: Bristol-Myers K.K.

X-ray diffraction and domain observation were performed to evaluate an effect of Nd-rich phase on the c-axis orientation of the Nd–Fe–B melt-spun ribbon. It was found that adequate addition of Nd-rich phase promotes the c-axis orientation of the Nd–Fe–B ribbon. The (Nd2Fe14B1)95(Nd-rich phase)5 ribbon has c-axis orientation in the entire body from bottom to top when melt-spun at wheel speed of 10.0 m/s.

1. The effect of a new rifamycin derivative, rifalazil (KRM-1648), on liver microsomal enzyme induction was studied in rat and dog with repeated oral administration of the compound. Relative liver weight, cytochrome b5 and P450 contents, enzyme activities of NADPH-cytochrome c reductase, aniline hydroxylase, p-nitroanisole O-demethylase, aminopyrine N-demethylase, and erythromycin N-demethylase were measured. 2. In rat, rifalazil treatment at 300 mg/kg/day for 10 days increased cytochrome b5 content but it did not affect liver weight, P450 content or enzyme activities. In contrast, rifampicin and rifabutin increased relative liver weights, cytochrome contents and enzyme activities under similar conditions. 3. In dog, rifalazil did not affect any parameters at 30 or 300 mg/kg/day for 13 weeks. 4. These findings indicate that rifalazil is not an enzyme inducer in rat and dog. This property differs from other rifamycin derivatives such as rifampicin and rifabutin.

The protease inhibitors, ritonavir, indinavir and saquinavir, the most potent anti-HIV drugs developed to date, interact with many drugs by competing for CYP3A4, an enzyme central to the metabolism of a wide variety of compounds. Human liver microsomes were used to compare inhibition by these three protease inhibitors. The inhibition was the greatest with ritonavir and indinavir and less potent with saquinavir.

Ferroelectric thin films as the recording media of scanning probe microscope-based storage devices were investigated using an atomic force microscope(AFM) technique. Polarization domains were formed in the PbZrxTi1-xO3(PZT) thin films epitaxialy grown on the epitaxial SrRuO3(SRO) thin films on SrTiO3 substrate by applying a pulse voltage between the conductive tip of AFM and SRO as a bottom electrode. The polarized domains were observed by detecting the inverse-piezoelectricity-induced surface vibration of the PZT thin film caused by applying an ac modulation voltage to the conductive tip. The recording density of polarized domains, domain switching speed and preliminary retention characteristics of polarized domains were studied. The polarized domains as small as 30 nm are formed in the PZT thin film with the thickness of 45 nm. The small domains can be formed by applying a 100 ns pulse of 10 V to the conductive tip. As for the retention characteristics of polarized domains with a size of 90–110...

Although various antimicrobial agents exhibit appreciable microbicidal activity in the early phase (weeks 2 t0 4) of Mycobacterium avium complex (MAC) infection induced in mice, progressive bacterial regrowth subsequently occurs. To clarify the reason for this pattern of changes, we studied changes in the levels of various cytokines in tissue at sites of infection (spleens and lungs) of MAC-infected mice which were or were not given a benzoxazinorifamycin, KRM-1648 (KRM). Levels of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha) and gamma interferon (IFN-gamma) in tissues temporarily increased at around weeks 2 to 4 after infection, rapidly decreased thereafter, and returned to normal by week 8. Similar but somewhat delayed changes were noted for levels of interleukin 10 (IL-10) and transforming growth factor beta (TGF-beta), immunosuppressive cytokines with macrophage (M phi)-deactivating activity, in tissue, except that TGF-beta levels in the spleen remained high during weeks 4 to 8. KRM treatment blocked the increase in the levels of all of those cytokines in tissue in the early phase of infection, most strongly at week 4. IL-6 levels were beneath the limit of detection throughout the observation period. Bacterial loads in the visceral organs decreased during the first 2 weeks, and KRM treatment markedly promoted this decrease. However, regrowth of MAC organisms began at weeks 2 to 4 and continued thereafter, even in KRM-treated mice. Splenocytes and splenic M phi s of MAC-infected mice (week 2) produced and/or released into the culture fluid significant amounts of TNF-alpha (in a cell-bound form), IFN-gamma, and IL-10, but not TGF-beta, during 3 days of cultivation. A substantial amount of TGF-beta was produced during 2 weeks of cultivation of peritoneal M phi s. KRM itself did not significantly affect the IL-10- and TGF-beta-producing ability of cultured M phi s. These findings suggest that IL-10 and TGF-beta play important roles in the regrowth of MAC organisms seen during the course of KRM treatment.

Dyskeratosis congenita (DC) is a rare inherited multisystem disorder caused by mutations in seven genes involved in telomere biology, with approximately 20% of cases having pulmonary complications. DKC1 mutations exhibit a severe disease phenotype of DC that develops in early childhood. Here, we report a unique case of DC with pulmonary fibrosis diagnosed at the age of 46. A novel missense mutation(p.Arg65Lys) of DKC1 was detected, and predicted to show a weak mutagenic effect. In spite of the steroid and immunosuppressive treatment, he died of an acute exacerbation seven months after the initial visit. This case suggests that mutation subtypes can cause heterogeneity in DC and pulmonary fibrosis.

The pharmacokinetics of 3'-hydroxy-5'-(4-isobutyl-1-piperazinyl) benzoxazinorifamycin (KRM-1648) in rats and dogs given a single oral dose of 3, 30, or 100 mg/kg of body weight were studied. In the rats, the concentrations of KRM-1648 in plasma, whole blood, and tissues peaked between 2.0 and 24.0 h, with elimination half-lives ranging from 6.2 to 19.5 h. The peak concentrations and the areas under the concentration-versus-time curves (AUC) for whole blood and tissues were 2 to 277 times higher than those for plasma. The high levels of KRM-1648 in tissues were consistent with its large volume of distribution (in excess of 10 liters/kg). A nonlinear increase in peak concentrations and AUCs for plasma, whole blood, and tissues occurred as the dose was increased and was consistent with the dose-dependent decrease in bioavailability. In the dogs, KRM-1648 levels in plasma and whole blood also exhibited a late time to the peak concentration (ranging from 4.0 to 11.2 h), a long elimination half-life (ranging from 15.2 to 24.0 h), and nonlinear kinetics. KRM-1648 exhibited high levels of plasma protein binding (more than 99%) and a high degree of affinity for lipoproteins in the plasma of both animals. After administration of KRM-1648, measurable levels of its metabolites, 25-deacetyl KRM-1648 in rats and 25-deacetyl KRM-1648 and 30-hydroxy KRM-1648 in dogs, were found in the biological samples tested. Thus, KRM-1648 is characterized by a high tissue affinity, a long elimination half-life, and nonlinear pharmacokinetics.

On 1992 we started the study of 500kg-class satellite mainly for technology demonstration mission which contributes to mitigate the project risk. It goes without saying that this class of satellite is characterized by low cost and fast turn-around-time, but are different from the same class satellites which we'd developed in the '80s. In this paper, we present the outline of this class of satellites, and focusing to Space Environments and Effects Observation Satellite(SEES) under pre-phase A. A lot of failures which have happened on orbit are caused by space environments. So it is necessary to understand in detail the behavior, and to develop technology to endure them.

Fracture tests for the verification of WPS (warm prestressing) effect were carried out by using large flat specimens with very low toughness. Tensile and bending loads and thermal shock were applied simultaneously to the specimens with the realistically postulated flaw and the two times larger one in order to make the maximum K{sub I} cross the lower bound of K{sub IC} data. During the tests, loading was controlled to simulate the shape of K{sub I} versus temperature curve for the postulated PTS transient. Both the specimens did not break within the scatter band of K{sub IC} when K{sub I} was decreased during cooling. K{sub I} values at fracture by reloading were beyond the upper bound of K{sub IC}. That is, the effectiveness of WPS was directly demonstrated for the PTS transients. Also, K{sup I} values at fracture can be predicted by Chell`s theory. As the test results, Japanese PWRs have sufficient temperature margin against PTS.

Pressurized thermal shock (PTS) is a phenomenon that can occur in the reactor pressure vessels (RPVs) with internal pressure and is one of the most severe stress conditions that can be applied to the vessel. Preliminary research has shown that no PTS concern is likely to exist on Japanese RPVs during their design service lives. However, public acceptance of vessel integrity requires analyses and experiment in order to establish an analytical method and a database for life extension of Japanese RPVs. The Japanese PTS integrity study was carried out from FY 1983 to FY 1991 as a national project by Japan Power Engineering and Inspection Corporation (JAPEIC) under contract with Ministry of International Trade and Industry (MITI) in cooperation with LWR utilities and vendors. Here, a crack arrest test was carried out using a toughness gradient steel plate with three layers to study the concept of crack arrest toughness. Four-point bending load with thermal shock was applied to the large flat plate specimen with a surface crack. Five crack initiations and arrests were observed during the test and the propagated crack bifurcated. Finally, cracks were arrested at the boundary of the first and the second layer, except for a smallmore » segment of the crack. The first crack initiation took place slightly higher than the lower bound of K{sub Ic} data obtained by ITCT specimens. That is, the K{sub IC} concept for brittle crack initiation was verified for heavy section steel plates. The first crack arrest took place within the scatter band of K{sub Ia} and K{sub Id} data for the first layer. That is, the K{sub Ia} concept appears applicable for crack arrest of a short crack jump.« less

The in vitro and in vivo activities of a new benzoxazinorifamycin, KRM-1648 (KRM), against Mycobacterium tuberculosis were studied. The MIC at which 50% of the isolates are inhibited (MIC50) and the MIC90 of KRM for 30 fresh isolates of M. tuberculosis measured by the BACTEC 460 TB System were 0.016 and 2 micrograms/ml, respectively. These values were much lower than those for rifampin (RMP), which were 4 and >128 micrograms/ml, respectively, and considerably lower than those for rifabutin (RBT), which were 0.125 and 8 micrograms/ml, respectively. A correlational analysis of the MICs of these drugs for the clinical isolates revealed the presence of cross-resistance of the organisms to KRM and either RMP or RBT although the MICs of KRM were distributed over a much lower range than were those of the other two drugs. KRM and RMP at concentrations of 1 to 10 micrograms/ml almost completely inhibited the bacterial growth of RMP-sensitive strains (H37Rv, Kurono, and Fujii) of M. tuberculosis phagocytosed in macrophage-derived J774.1 cells. KRM was more active than RMP in inhibiting the growth of the RMP-resistant (MIC = 8 micrograms/ml) Kurata strain but failed to show such an effect against the RMP-resistant (MIC >128 micrograms/ml) Watanabe stain. When KRM was given to M. tuberculosis-infected mice at dosages of 5 to 20 mg/kg of body weight by gavage, one daily six times per week from day 1 after infection, it was much more efficacious than RMP against infections induced in mice by the RMP-sensitive Kurono strain, as measured by a reduction of rates of mortality, a reduction of the frequency and extent of gross lung lesions, histopathological changes in lung tissues, and a decrease in the bacterial loads in the lungs and spleens of infected mice. KRM also displayed significant therapeutic efficacy against infection induced by the RMP-resistant Kurata strain, while neither KRM nor RMP was efficacious against infection by the RMP-resistant Watanabe strain. In the case of infection with the Kurono strain, the efficacy of the drugs in prolonging the time of survival was in the order KRM, RBT, RMP. KRM was much more efficacious than RMP, when given at 1- to 4-week intervals. These findings suggest that KRM may be useful for the clinical treatment of tuberculosis contracted through RMP-sensitive strains, even when it is administered at long intervals.

Preparation and magnetic properties of Sm2Fe17Nxα-Fe composite magnets obtained by HDDR method have been investigated. Sm-Fe alloys prepared by arc melting were rapidly quenched at a surface velocity of Vs=50 m/s. These as-quenched ribbons, containing 6∼8 at%Sm, possessed a Sm-Fe phase of TbCu7-type. After HDDR treatment, a Th2Zn17-type Sm-Fe phase and an α-Fe phase were observed. Sm2Fe17Nx+α-Fe composite magnets were obtained by subsequent nitrogenation. Nitrogenated Sm8Zr2Fe90 powders exhibited high magnetic properties with σm=115 emu/g and HcJ=12.4 kOe, after applying magnetization field of 50 kOe. These powders showed σr/σm ratio of 0.63 without demagnetization correction.

A negative-tone photo-definable polyimide with a low CHE has been developed for coating suspension heads in HDD applications. In order to select the low CHE polyimide, the stabilization energy of hydration calculated from the polyimide and water by Gaussian 03 was used as an indicator. A good correlation between the stabilization energy and CHE value of the polyimide was obtained and which resulted in the development of a low CHE, negative-tone, photo-definable polyimide. The developed material has a low CHE of 9 ppm/%RH, a CTE of 17 ppm/°C (matching that of stainless steel) and good lithographic properties.

We investigated the influence of AC voltage prestressing on the electrical-tree inception voltage in LDPE. When AC voltage prestress was not imposed, the impulse-tree inception voltage increased with the size of water tree due to the electrical field relaxation. On the other hand, when AC voltage prestress was imposed, the impulse-tree inception voltage did not change with the water-tree size and was lower than that without AC voltage prestressing. The FTIR absorption measurements showed several absorptions between 650 and 1500 cm−1, which did not exist in the sample without AC voltage prestressing. Besides, the TEM observation revealed that the AC voltage prestressing increased the density and size of micro voids and some of them were aligned in the direction of applied electric field. These results suggest that AC voltage prestressing causes structural change in the water tree and enhances material degradation, leading to lower tree-inception voltage.

Fracture tests for the verification of WPS (warm prestressing) effect were carried out by using large flat specimens and big compact specimens with low toughness. In the case of monotonical KI increasing during cooling, the specimen broke within the scatter band of KIC. On the other hand, when KI was decreasing during cooling, the specimens did not break even if KI values were beyond the scatter band of KIC. That is, WPS effect was confirmed even for the low toughness steel like reactor pressure vessel wall under neutron irradiation. Also, KI values at fracture can be predicted by Chell’s theory. By applying WPS effect and the predictive equations for irradiation embrittlement for Japanese PWR reactor steels to the PTS integrity analysis, much more temperature margin can be expected.

We have fabricated 77 K deep-submicron MOSFETs on the basis of the temperature-dimension combination scaling theory (CST). The 77 K MOSFETs with 1-V supply voltage are designed from a 300 K MOSFET with 4-V supply voltage. The fabricated 77 K 0.18 /spl mu/m device has exhibited fully scaled characteristics. The subthreshold swing (S) and the threshold voltage (V/sub th/) of the 77 K device are found to be 1/4/spl ap/77 K/300 K of those of the 300 K device. Furthermore, S and V/sub th/ are achieved to be 27 mV/dec and 0.21 V without short-channel effect degradation. >

Trimethylamine-alane (AlH 3 N(CH 3 ) 3 , TMAAl) is an attractive precursor to reduce oxygen and carbon incorporation in the growth of AlGaAs films. However, a gas-phase reaction between TMAAl and triethylgallium (TEG) has been reported, and this prevents the premixture of the group III sources to have compositional uniformity in chemical-beam epitaxy (CBE) or metalorganic molecular-beam epitaxy. In this paper, a new TEG adduct is proposed to prevent the gas-phase reaction. The gas-phase reaction with TMAAl is shown to be effectively suppressed using the TEG adduct

Japanese pressurised thermal shock (PTS) integrity study has been carried out to obtain public acceptance of reactor pressure vessels integrity against PTS events and to provide the data base for their life extension. This paper introduces a research plan and results.

A deletion of about 4 kb has been determined in the mutated mitochondrial DNA (mtDNA) in cardiomyocytes with chronic doxorubicin (DOX)-induced cardiotoxicity in mouse. The incidence of the mtDNA deletion increased with the dosage and with the duration of the DOX administration. Coenzyme Q10 administration prevented the mtDNA deletion and decreased the thiobarbituric acid reactive substance content in the heart mitochondria, suggesting some free radical involvement in this mtDNA deletion. This mtDNA deletion may be involved in cardiomyopathy, which is known to be dosage-dependently induced by DOX administration.

Effects of carperitide (alpha-human atrial natriuretic peptide) on hemodynamics and renal function in dogs with congestive heart failure (CHF) produced by volume expansion and ligation of the left anterior descending coronary artery were compared with those of various anti-heart failure agents (cardiotonic, vasodilator and diuretic). Carperitide (0.1-1 microgram/kg/min) dose-dependently decreased the elevated left ventricular end-diastolic pressure (LVEDP). No significant changes in cardiac contractility (LV dP/dtmax) and heart rate (HR) were noted, although cardiac output (CO) tended to reduce during the infusion of carperitide. Nitroglycerin (NG; 3 micrograms/kg/min) and furosemide (1 mg/kg) also decreased LVEDP, but the potency was less than that of carperitide. Sodium nitroprusside (SNP; 10 micrograms/kg/min) and dobutamine (10 micrograms/kg/min) caused a reduction in LVEDP and increased CO with an increase in HR. Hydralazine (H; 100 micrograms/kg/min) increased CO without reduction in LVEDP and induced a pronounced increase in HR. Double product (systolic blood pressure x HR), an index of myocardial oxygen consumption, was significantly reduced by carperitide, but significantly increased by DB and H. Carperitide, unlike NG, SNP, H and DB, increased urine volume and urinary electrolyte excretion. These results suggest that carperitide will be an useful therapeutic agent for the treatment of CHF.

MICs of a newly developed benzoxazinorifamycin derivative, KRM-1648, for Mycobacterium avium complex (MAC) were determined by the BACTEC 460 TB system and compared with those of other known antimicrobial agents. The radiometric method gave a fast, accurate, and reproducible MIC for each antimicrobial agent. MICs of KRM-1648 for 30 strains of MAC (10 strains each of M. avium isolated from AIDS and non-AIDS patients and of Mycobacterium intracellulare isolated from non-AIDS patients) were measured. The MICs, ranging from 0.004 to 0.0625 microgram/ml, were the lowest of all tested drugs, including rifampin, rifabutin, streptomycin, kanamycin, isoniazid, ethambutol, ofloxacin, ciprofloxacin, sparfloxacin, and clarithromycin. The MICs were 2 to 512 and 1 to 32 times lower than those of rifampin and rifabutin, respectively. With rifampin and ethambutol, there were some differences between the MICs for M. avium isolated from AIDS patients (American) and those for M. avium from non-AIDS patients (Japanese). Moreover, appreciable differences between the MICs of some drugs against M. avium and M. intracellulare isolated from non-AIDS patients were found. Many strains of M. avium were more susceptible to ofloxacin than M. intracellulare, but, conversely, M. avium was more resistant to rifampin, streptomycin, ethambutol, and clarithromycin than M. intracellulare.

Small losses of NaCl, KBr, TICI, KRS-5, CsI, and PbI(2) near 10 microm were measured using an improved differential infrared spectrophotometer with an accuracy better than 0.1% in transmittance. TlCl shows relatively large intrinsic multiphonon absorption, whereas the others show only impurity loss. PbI(2), with the possibility of glass formation, shows its infrared absorption proportional to exp(-omega/37.5), where omega is the frequency in cm(-1).

The current chapter reveals that marriage is the 'natural' destiny for all the participants in this study, whereas parenthood is no longer seen as fate in Cohort Three. Despite the fact that many participants lacked experience of intimate relations with the opposite sex, this gender chasm was resolved by arrangements for marriage by third parties. The first section of this chapter looks at the participants' development of sexual identity in conjunction with adolescence and dating. The next section explores the patterns, and social and personal meanings, of marriage. Physical maturation at puberty is a significant factor in adolescence and it is important to pay attention to cultural and societal interpretations of physical changes because the cultural and social meanings given to the changes embody gender relations. Girls and boys are aware of their own bodily changes, as well as those of the opposite sex.Keywords: adolescence; cohort three; gender relations; Marriage; physical maturation; sexual identity; societal interpretations

This chapter illuminates what Connell calls the "gender regime" of the school through the experience of the participants. Beginning with a brief discussion of the academic trajectory of the participants in this study, various aspects of schooling such as the structure of the school, the gender of the teachers, discipline and peer culture are examined. The latter half of this chapter discusses sport in the context of physical education as well as of extra-curricula activities outside school regulations, exploring sex-segregation and hierarchy among the participants. While a little more than fifty per cent of male junior high school students enrolled in high school, just forty per cent of female students went on to high school. Masculinity depends on the physical and psychological power that men embody. Sports, which occupy an important part of the identity development of little boys into young men, provide us with an insight into male embodiment.Keywords: Connell; gender regime; masculinity; psychological power; school; sex-segregation; up: Gendered experiences

Recent observations on the non-hydrogen isotopic effect shed new light on the nature of the displacive type and order-disorder type ferroelectric phase transitions in dielectrics. The isotopic effect on Tc is discussed in relation to the hydrostatic pressure effect on Tc and the band-gap shifts induced by transitions. It is shown that these phenomena are strongly correlated in these types of transition. Also, it is concluded that the displacive-type transition is due to the quantum-mechanical electron-phonon interaction in those crystals.

Tentoxin is an interesting non-specific toxin produced by some Alternaria species, known as pathogenic organisms. The high-performance liquid chromatographic determination of tentoxin by using a YMCA-312 column, a reversed type of octadecylsilica, with 0.05 M ammonium dihydrogenphosphate—acetonitrile (7:3) as the mobile phase is described. The limit of detection is 0.1 μg/ml. One assay can be performed by using culture liquid without any other procedures within 30 min.

We have clearly demonstrated a single spot in a far-field pattern of nitride-based laser diodes with a thick n-AlGaN layer/low-temperature-deposited buffer layer/sapphire. This AlGaN-based structure has realized a crack-free 1-μm-thick n-type Al0.06Ga0.94N cladding layer, leading to suppression of optical leakage from the waveguide region to the underlying layer and improvement of optical confinement. The threshold current of the laser diode is about 230 mA, which is comparable to or better than that of our laser diodes with the conventional GaN-based structure.

To evaluate the efficacy and safety of leukocytapheresis (LCAP) in patients with rheumatoid arthritis (RA) that is refractory to disease modifying antirheumatic drugs (DMARDs), we conducted a prospective, multicenter, open-label clinical trial.We enrolled 38 active RA patients, including 32 patients who showed an inadequate response toor = 2 DMARDs and 6 patients with rapidly progressive RA. All patients continued drug therapy and were treated with 5 LCAP sessions conducted at 1-week intervals. The clinical response was evaluated at baseline before starting LCAP and at 4 weeks after the completion of all the LCAP sessions using the American College of Rheumatology (ACR) criteria and the 28-joint disease activity score (DAS28) of the European League Against Rheumatism (EULAR).Of the 35 patients who fulfilled the study's eligibility criteria, 24 (69%), 10 (29%), and 23 (66%) patients achieved 20% (ACR20), 50% (ACR50), and DAS28-C-reactive protein (CRP) EULAR improvement, respectively. The mean DAS28-CRP score of the 35 patients decreased significantly from 5.99 +/- 0.92 at baseline to 4.54 +/- 1.39 after treatment. Comparison analysis of the ACR20 responders and non-responders to LCAP revealed that 22 of 24 responders (92%) concomitantly received methotrexate, whereas significantly fewer, that is, 6 of 11 non-responders (55%) received methotrexate. Less frequent and transient mild-to-moderate adverse events, including nausea and headache, were seen in 12 of 189 LCAP sessions (6.3%).These results demonstrate the usefulness of LCAP in combination with DMARDs, particularly methotrexate, as an effective and safe treatment for refractory RA.

The Japanese Pressurized Thermal Shock (PTS) integrity study is now being conducted by the Japan Power Engineering and Inspection Corporation (JAPEIC) under contract with the Ministry of International Trade and Industry (MITI). This paper introduces the study plan and the interim results on irradiation embrittlement of reactor pressure vessel steels. Five kinds of base metal plates and two kinds of weld metals were irradiated in the Japan Material Testing Reactor (JMTR). After irradiation, Charpy test and fracture toughness (KIC, JIC, KId, JId) test were conducted. Principal results are as follows. 1. (1) Change of material properties of some Japanese reactor pressure vessel steels caused by neutron irradiation was obtained. 2. (2) Predictive equations of irradiation embrittlement ΔRTNDT for Japanese PWR reactor pressure vessel steels were developed.

In this report, we present feasibility of our newly developed laser device for prospective human fetoplacental surgery. Fetuses having congenital fetoplacental anomalies, if untreated before birth, occasionally deteriorate in utero with high perinatal mortality and/or morbidity. If this is the case, outcomes of conventional postnatal care might be quite unrewarding medically as well as economically. Although the advent of minimally invasive fetal endoscopic laser treatment (fetoscopic laser photocoagulation, FLPC) has strikingly improved the natural history of fetuses with twin-twin transfusion syndrome (TTTS), this underwater unique surgery is still technically demanding depending on placental location, position of floating twins, gestational age, and fetomaternal obstetrical conditions. In an attempt to resolve most of these difficulties associated with FLPC, we developed a composite-type optical fiber scope that enables transmission of laser light and endoscopic images concurrently. This technology is a spin-off of our research works on the International Thermonuclear Experimental Reactor (ITER) at Japan Atomic Energy Agency and the device is an integrated system consisting of a composite-type optical fiber scope (2 mm in OD), a coupling device for transmission/distribution of laser light along with object images, a laser light source and a magnified image monitoring system. A lens made by quartz is installed on the tip of composite-type optical fiber scope. It has the resolution of about 9,000 pixels and the angle of view of 54 degrees. In addition, it can transmit the 40W laser energy with a focal length of 10 mm. Clinically, the composite-type optical fiber scope, if mounted on our multi-DOF robotic manipulator, is supposed feasible for much more accurate identification and coagulation of the target placental vessels responsible for TTTS pathophysiology. Our current state of the art will be presented in detail along with basic test results.

A 10-nm-thick PbZr0.25Ti0.75O3 thin film is epitaxially grown on a SrRuO3/BaTiO3/ZrO2/Si heterostructure substrate by reactive evaporation. Structural and electrical properties of the film are investigated. It is concluded that the film is ferroelectric and retains a native uniform upward polarization. Artificial downward polarization domains, whose average diameter is 24 nm, can be formed in the film.