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Background Golimumab (GLM) is an anti-TNF-α drug approved for treating ulcerative colitis (UC). Although its efficacy and safety were well established in clinical trials, real-world evidence was still limited. In the present study, we evaluated 52-week effectiveness and safety of GLM treatment for UC based on post-marketing surveillance data. Methods The prospective, post-marketing study was conducted in 393 patients from 163 medical facilities. Patients who had been prescribed GLM were enrolled between May 2017 and September 2019 in Japan. In accordance with Japanese indication, patients received subcutaneous injections of GLM, 200 mg at week 0, 100 mg at weeks 2 and 6, followed by 100 mg every 4 weeks. Clinical remission (partial Mayo score ≤2), predictors of remission, adverse drug reactions (ADRs), and predictors of ADR development were determined at week 52. Results Of 393 enrolled patients, 391 and 386 were included in safety and efficacy analysis set, respectively (Table 1). Overall, clinical remission in the intention-to-treat population was 13.0%, 53.9%, 52.6%, 48.2%, and 43.3% at baseline (BL) and at week 6, 22, 36, and 52, respectively (Table 2). In biologic naïve group, clinical remission was 9.2%, 59.1%, 61.0%, 52.4%, and 47.0% at BL and week 6, 22, 36, and 52, respectively, while in biologic experienced group, it was 15.8%, 50.0%, 46.4%, 45.0%, and 40.5% at BL and week 6, 22, 36, and 52, respectively. At week 52, clinical remission rate in the patients who concomitantly used corticosteroid (CS) at BL was significantly lower than that in the patients who did not receive CS (p=0.017, 37.3% vs 49.2%) (Fig. 1). No significant difference in remission rate was observed between immunomodulator (IM) users and IM non-users at baseline. From multivariate analysis, concomitant use of CS (p=0.001, odds ratio [OR] =0.488, 95% CI [confidence interval] 0.314–0.759) and partial Mayo remission at BL (p Conclusion From the Japanese post-marketing data, the real-world effectiveness of GLM treatment was confirmed in both biologic naïve and experienced populations. Safety profile was generally consistent with previous findings, and no additional safety signals were identified. Concomitant use of CS, but not IM, may be likely to affect outcome of GLM therapy.

Funding Acknowledgements Type of funding sources: Other. Main funding source(s): Private grant from Kowa Pharmaceuticals to Brigham and Woman's Hospital Calcific aortic valve stenosis (CAVS) is the most prevent valvular heart disease in the western world increasing exponentially with age, with an 112% increase in CAVS deaths in the last three decades; however no therapeutic treatment is currently available. Recently, lipoprotein(a) [Lp(a)] has been demonstrated to be an independent and causal risk factor for CAVS, yet the understanding of its cellular uptake and catabolism is limited thus underscoring the need for further investigation. This study aimed to determine a target receptor, unique for Lp(a) on the surface of valvular interstitial cells (VICs) and ascertain the role of the receptor on the development of VIC calcification. Unbiased ligand-receptor capture mass spectrometry (TriCEPS) was used to identify target receptor, with western blotting, ELISA, qPCR, alizarin red calcium staining and immunofluorescence used to validate the targets in vitro via siRNA inhibition and overexpression. Transmission electron microscopy (TEM) was used to determine uptake of Lp(a) within excised human valves. Identification of small molecule inhibitors was assessed computationally via the L1000 dataset, with the top hit candidate validated in vitro. Genotype-phenotype studies were examined using the United Kingdom Biobank (UKBB) and the Millions Veterans Program. Linear regression was used to evaluate association between aortic stenosis and plasma Lp(a) levels, and a phenotype-wide association analysis was then performed against this generated ‘genotype’. Ligand-receptor capture mass spectrometry was used to detect novel membrane proteins with specific binding to Lp(a); MFSD5, MRC2, LDLR were identified as possible candidates. MFSD5 RNAscope demonstrated its presence in human aortic valves. Lp(a) uptake in VICs was confirmed via western blot and TEM. MFSD5 siRNA significantly reduced dil-labelled Lp(a) uptake in human VICs (p=0.003) and HEPG2 cells (p=0.0003), conversely MFSD5 overexpression increased uptake (p=0.0345, p=0.0318), whilst specificity of MFSD5 to Lp(a) alone was shown via no change in LDL uptake following MFSD5 inhibition (p=0.616, p=0.991). MFSD5 inhibition reduced RUNX2 (p=0.0124) and Osteocalcin (p The current study demonstrates the novel Lp(a) receptor MFSD5 may be responsible for uptake of Lp(a) within VICs, resulting in the development of aortic valve calcification, highlighting the need for further exploration into the role of MFSD5 in aortic valve disease.

A newly developed laser system is adopted in this study as a surface preparation method for corroded steel structures. To investigate the thermal effects of laser beam on steel material, carbon steel plates are treated by two different laser processing parameters. Then the surface condition, heat-affected zone, and iron oxide on laser-treated specimens are evaluated using optical microscope, SEM-EDX, and XRD. Moreover, a severely corroded steel member was used as laser irradiation target to verify the cleaning effects of laser beam. Results show that surface morphologies are varied according to laser processing parameters. Due to thermal effects, iron oxide was formed after laser irradiation, and higher laser power induced deeper heat-affected zone. The application of laser treatment for corroded steel member showing desirable surface cleanliness after laser irradiation. The laser surface treatment could be an alternative surface preparation method for steel structures in the construction field.

The paper “A decision making system using Deep Learning for earthquake prediction by means of electromagnetic precursors”’ was submitted at the EMSEV 2018 International Workshop (Electro-Magnetic Studies of Earthquakes and Volcanoes-“Integrating Geophysical Observations from Ground to Space for Earthquake and Volcano Investigations”), it was accepted, it was presented and included in the conference proceedings

We investigate the angular distribution of scission particles taking account of the effects of fission fragments. The time evolution of the wave function of the scission particle is obtained by integrating the time-dependent Schrodinger equation. The effects of the fission fragments are taken into account by means of the optical potentials. The angular distribution is strongly modified by the presence of the fragments. The attractive nuclear potential enhances the yield along the fragment axis for both neutrons and protons. For scission protons, the focusing effect due to the repulsive Coulomb field of the fragments is demonstrated. In the case of asymmetric fission, it is found that the heavy fragment has stronger effects.

We investigate the effects of the fission fragments on the angular distribution of scission neutrons. The time evolution of the wave function of the scission neutron is obtained by integrating the time-dependent Schrodinger equation. The effects of the re-absorption and scattering by the fission fragments are taken into account by means of the optical potential. The angular distribution is strongly modified by the presence of the fragments. Dependence on the magnitude of the absorption is discussed. Influence of the finiteness of the grid size is also discussed.

We have performed Ce ${L}_{3}$-edge x-ray absorption spectroscopy (XAS) and Ce $4d\ensuremath{-}4f$ resonant photoemission spectroscopy (PES) on single crystals of ${\mathrm{CeO}}_{1\ensuremath{-}x}{\mathrm{F}}_{x}{\mathrm{BiS}}_{2}$ for $x=0.0$ and 0.5 in order to investigate the Ce $4f$ electronic states. In Ce ${L}_{3}$-edge XAS, a mixed valence of Ce was found in the $x=0.0$ sample, and F doping suppressed it, which is consistent with the results on polycrystalline samples. As for resonant PES, we found that the Ce $4f$ electrons in both $x=0.0$ and 0.5 systems respectively formed a flat band at 1.0 and 1.4 eV below the Fermi level and there was no contribution to the Fermi surfaces. Interestingly, Ce valence in ${\mathrm{CeOBiS}}_{2}$ deviates from ${\mathrm{Ce}}^{3+}$ even though Ce $4f$ electrons are localized, indicating the Ce valence is not in a typical valence fluctuation regime. We assume that localized Ce $4f$ in ${\mathrm{CeOBiS}}_{2}$ is mixed with unoccupied Bi $6{p}_{z}$, which is consistent with a previous local structural study. Based on the analysis of the Ce ${L}_{3}$-edge XAS spectra using Anderson's impurity model calculation, we found that the transfer integral becomes smaller, increasing the number of Ce $4f$ electrons upon the F substitution for O.

Bi2Sr2CaCu2O8+δ (Bi-2212) stacks of intrinsic Josephson junctions were fabricated by an acid-treatment process from inside a single crystal. The surrounding acid-treated product is a transparent material, BiOCl. During the process, an optical adhesive (NOA-61) was used to fix a piece of the crystal on a glass substrate and to coat the surface of the sample. The current-voltage characteristics of the stacks at T = 77 K exhibited large hystereses and multiple branches with voltage spacings of approximately 2-3 mV. Under an external microwave field in the frequency range of 2-18 GHz, clear Shapiro steps were observed at voltages with multiples of (h/2e)frf. In addition, the thermal cycling properties of the critical current (Ic) were investigated. No apparent degradation of the Ic was observed during repeated thermal cycling between 300 and 77 K.

Lattice-mismatched-strain-driven, defect-free, 3-D islands, dubbed self-assembled quantum dots (SAQDs), currently provide the most advanced platform for quantum-dot-based devices with successful applications to SAQD lasers and considerable potential for infrared detectors. For the latter, one of the limitations is the short optical path length owing to the difficulties in creation of large numbers of quantum dot layers without formation of structural defects arising from accumulated strain. This limitation can be considerably overcome by creation of an appropriate resonant cavity to enhance the optical field in the SAQD regions. In this paper, we demonstrate resonant-cavity-enhanced quantum dot infrared photodetectors in the mid-infrared (MIR, 3-5 μm ) regime. For effective enhancement, the SAQDs are designed to generate a very narrow peak (Δλ/λ ~ 10%) in the intraband photocurrent response in the MIR range utilizing short period superlattices as the quantum confining layers. Incorporating such SAQD layers at specific enhanced electric field regions within the resonant cavity comprising a two-pair GaAs/air-gap back mirror and a GaAs surface front mirror, we have obtained QDIP detectivity enhancement of ~ 8-12 times.

This paper describes results obtained from analysis and experiments done on a fluxgate dc earth leakage current sensor for electric vehicles and photovoltaic power generation systems. As fluxgate current sensors are extremely sensitive to room temperature, various applications need this characteristic. However, conventional fluxgate current sensors have a problem in that they can only measure a narrow range of currents. To address this issue, we propose that the turns of the excitation coil be optimized with a simulator. This new sensor consists of a coiled wire that is wound around a toroidal amorphous core and through a bus bar. The sensor detects variations in excitation current according to dc current. The sensor was analyzed with a simulator. The magnetic field simulator was used to calculate the excitation current, and the output voltage according to the excitation current was calculated with a circuit simulator. We found that the results from simulations almost corresponded to those from measurements, and were able to verify the validity of the basic analytical model. As a result of analysis with the simulator, 35 turns of the excitation coil were used to achieve a wide range of measurements of ±600 mA.

We have developed a high-strength Ta-reinforced conductor for high-magnetic-field magnets. In our previous work, it was demonstrated that the Ta-reinforced conductor had good characteristics against mechanical stress and strain. In this study, we made a 2-D calculation code for a stress-strain analysis, and derived the stress and strain of the magnet using some physical values such as the Young's modulus of the conductors, magnet dimensions and so on. According to the calculation results of some model magnets, the Ta-reinforced conductor could be used without extra support structures. Hence, the conductors are fit for high-magnetic-field and large-scale magnets such as NMR and SMES magnets.

A YBCO coated conductor is expected to be a next generation high performance superconductor. To design superconducting machines using YBCO conductors, evaluation of not only superconducting properties but also mechanical properties is very important. Hence, we applied bending and torsion to the YBCO conductor and measured degradation of the conductor against the strain. To compare with the YBCO's data, a Bi2223 conductor was also tested under the same experimental condition. From the bending test, degradation of the Bi conductor was faster than that of the YBCO conductor and the critical current gradually decreased with increasing bending strain. The YBCO conductor kept better performance than the Bi conductor, and degradation suddenly occurred. And when the superconducting layer in the YBCO conductor was subjected to compressive strain in the bending test, the critical current hardly decreased at approximately one percent of the bending strain.

The aim of this study was to examine the effect of cytokines on different subsets of NK cells, while especially focusing on CD16(-) CD56(dim) cells and CD16(-) CD56(bright) cells. When human peripheral blood mononuclear cells (PBMC) were cultured with a combination of IL-2, IL-12 and IL-15 for several days, a minor population of CD56(bright) NK cells expanded up to 15%, and also showed potent cytotoxicities against various cancer cells. Sorting experiments revealed that unconventional CD16(-) CD56(+) NK cells (CD16(-) CD56(dim) NK cells and CD16(-) CD56(bright) NK cells, both of which are less than 1% in PBMC) much more vigorously proliferated after cytokine stimulation, whereas predominant CD16(+) CD56(dim) NK cells proliferated poorly. In addition, many of the resting CD16(-) CD56(bright) NK cells developed into CD16(+) CD56(bright) NK cells, and CD16(-) CD56(dim) NK cells developed into CD16(-) CD56(bright) NK cells and also further into CD16(+) CD56(bright) NK cells by the cytokines. CSFE label experiments further substantiated the proliferation capacity of each subset and the developmental process of CD16(+) CD56(bright) NK cells. Both CD16(-) CD56(dim) NK cells and CD16(-) CD56(bright) NK cells produced large amounts of IFN-gamma and Fas-ligands. The CD16(+) CD56(bright) NK cells showed strong cytotoxicities against not only MHC class I (-) but also MHC class I (+) tumours regardless of their expression of CD94/NKG2A presumably because they expressed NKG2D as well as natural cytotoxicity receptors. The proliferation of CD16(+) CD56(bright) NK cells was also induced when PBMC were stimulated with penicillin-treated Streptococcus pyogenes, thus suggesting their role in tumour immunity and bacterial infections.

We report 1H NMR results for (CH3)2NH2CuCl3measured at very low temperature down to 0.1 K using a dilution refrigerator. Field induced magnetic ordered state is revealed by the NMR measurements and a magnetic phase diagram for the system is proposed.

High-Tc superconducting (HTS) coils with various types of reinforcement are investigated with respect to the reduction of mechanical loss. The total AC loss of the coils is measured under an external DC magnetic field at liquid nitrogen temperature, the reduction of the mechanical loss components are estimated. Tensioned stainless-steel tape is found to be the most effective for reducing the mechanical loss by improving the rigidity of the entire winding. The mechanical loss of the HTS coils is reduced by reinforcement with a bobbin of negative thermal expansion material, although the hoop stress caused by radial expansion of the bobbin is absorbed by a small number of winding turns. Bobbins of negative thermal expansion material are therefore unsuitable for pancake-type coils or multilayer windings, but can be expected to realize substantial reductions in mechanical loss for single-layer windings or thin solenoids

A set of both the magnetic and electromagnetic shielding models, referred to as a new member of the Problem 21 family, is proposed to investigate the shielding effects of different kinds of shields. This paper presents the newly measured and calculated results of both the magnetic field and stray-field loss concerning the TEAM-based models to detail the electromagnetic behavior of the Problem 21 family, evaluates the engineering applicability of three-dimensional eddy current analysis methods, and validates the engineering effectiveness of the practical loss modeling proposed by the authors

Growth of secondary plasmodia of the clubroot pathogen Plasmodiophora brassicae was studied in dual culture of P. brassicae and turnip suspension cells. Suspension culture of P. brassicae-infected turnip cells was achieved by using P. brassicae-infected callus in Murashige and Skoog medium supplemented with 0·1 mg 2,4-D L−1 and 0·02 mg kinetin L−1. The shape of secondary plasmodia in suspension cells was spherical-to-subspherical. A few young plasmodia divided and became numerous spherical, small plasmodia which eventually formed a plasmodial cluster. The plasmodia fused and became vegetative plasmodia. Infected cells were significantly larger than noninfected cells. Secondary plasmodia moved within transformed turnip suspension host cells by cytoplasmic streaming of the host cells. Secondary plasmodia divided in synchrony with the transformed turnip cells.

In the study of the fission of actinide nuclei at low excitation energies including the spontaneous fission, it was found that the fragment mass distribution and the total kinetic energy (TKE) distribution consist of more than one component, in contrast to the simple single peak structure that is found in the fission at high excitation energies. 1– 6 This phenomenon is attributed to the existence of more than one fission path and is called the multi-modal fission. The mass and TKE distributions depend sensitively on the excitation energy and the position of the peaks of the mass distribution suggests the influence of the closed shell structure of the fragments. Therefore, it is supposed that the microscopic energy plays an important role for the manifestation of this phenomenon. It is a great challenge for us to understand this phenomenon in terms of nuclear many-body dynamics. Several authors studied the potential energy surface (PES) including the microscopic energy in a multi-dimensional parameter space that describes various nuclear shapes; one can deduce the possible fission paths by studying the location of the saddle points and the fission valleys in multi-dimensional parameter space. 7 With this method, they could explain the general trend of the position of the peaks of the mass distribution. The dynamical point of view is necessary to progress the study of the fission mode. We have applied the Langevin approach to the study of the fission modes in uranium nuclei and in fermium nuclei. 8–10 We studied the mass and TKE distributions and demonstrated that we can decompose the fission events into several components by tracing the Langevin trajectories. We also studied the isotope dependence and the excitation energy dependence of the fission mode. 8–10 In the previous studies, we adopted the wall-and-window type one-body friction as the dissipation mechanism of the nuclear fission dynamics. The validity of this dissipation mechanism has been demonstrated by one of the authors (T.W.) who studied the dissipation tensor dependence of the pre-scission neutron multiplicity and the mean TKE. 11–14 From the comparison of the results of the dynamical calculation with experimental data, they excluded the possibility of the two-body type dissipation to be the dominant mechanism by showing that it cannot reproduce the pre-scission neutron data and the TKE data simultaneously. On the other hand, they showed that the wall-and-window type one-body friction can reproduce both data reasonably well and concluded that it is a reasonable model for the dissipation mechanism of nuclear fission. There are other models that are of one-body nature, e.g. surface-plus-window formula, modified wall-and-window formula and chaos weighted wall formula. 15–17 Though there were no free parameters in the original derivation of the one-body friction, 18, 19 the strength has been modified frequently in order to reproduce some experimental data. For example, in the study of the light particle evaporation and the mass distribution, Schmitt et al. used the strength as a free parameter. 17 The modification itself should be acceptable when we take account of the simplicity of the model; it is a macroscopic model without any microscopic effect and it has no dependence on the temperature. However, when one modifies the strength of the nuclear dissipation just to reproduce only one physical quantity, it might be inappropriate to conclude that the deduced strength has definite physical meanings. It may reflect the other effects completely different from the dissipation, like the insufficiency of the model space. It is very important to compare many (at least more than one) physical quantities at the same time. Among the physical quantities that are measured in nuclear fission, the TKE and mass distributions are well investigated experimentally in many cases. In this study, we use these quantities to discuss the dissipation dependence of the fission modes. It is shown that the TKE distribution is, as was expected, directly connected to the strength of the dissipation and we can put some constraints on the strength of the dissipation. Furthermore, it is shown that the mass distribution changes rather drastically when one uses different models for the dissipation mechanism. These results demonstrate the importance and the usefulness of the dynamical approach to the study of the fission mode. Section 2 gives a concise description of our framework. Results are shown in Sec. 3 concerning the fission of 264 Fm nucleus at Ex = 20 MeV. Summary is given in Sec. 4. 2. Methods

KRN 8602 (MX2) is a novel morpholino anthracycline derivative having the chemical structure 3'-deamino-3'-morpholino-13-deoxo-10-hydroxycarminomycin hydrochloride. To investigate the mechanisms of resistance to MX2, we established an MX2-resistant phenotype (K562/MX2) of the human myelogeneous leukaemia cell line (K562/P), by continuously exposing a suspension culture to increasing concentrations of MX2. K562/MX2 cells were more resistant to MX2 than the parent cells, and also showed cross-resistance to etoposide and doxorubicin. Topoisomerase (Topo) IIalpha protein levels in K562/MX2 cells were lower of those in K562/P cells on immunoblot analysis and decreased expression of Topo IIalpha mRNA was seen in K562/MX2 cells. Topoisomerase II catalytic activity was also reduced in the nuclear extracts from K562/MX2 cells when compared with K562/P cells. Aberrant methylated CpG of Topo IIalpha gene was observed in K562/MX2 cells when compared with the parent line on methylation-specific restriction enzyme analysis. To overcome the drug resistance to MX2 and etoposide, we investigated treatment with 5-Aza-2'-deoxycytidine (5AZ), which is a demethylating agent, in K562/MX2 cells. 5-Aza-2'-deoxycytidine treatment increased Topo IIalpha mRNA expression in K562/MX2 cells, but not in K562/P cells, and increased the cytotoxicity of MX2 and etoposide. Methylated CpG was decreased in K562/MX2 cells after 5AZ treatment. We concluded that the mechanism of drug resistance to MX2 and etoposide in K562/MX2 cells might be the combination of decreased expression of Topo IIalpha gene and increased methylation, and that 5AZ could prove to be a novel treatment for etoposide-resistant cell lines, such as K562/MX2.

SUMMARYThe alanine-rich repeating region (A-region) in the surface protein antigen (PAc) of Streptococcus mutans has received much attention as an antigenic component for vaccines against dental caries. The PAc (residue 361–386) peptide in the A-region possesses a multiple binding motif (L- -V-K- -A) to various HLA-DR molecules and a B-cell core epitope (- Y- - -L- -Y- - - -) that recognizes the inhibiting antibody to S. mutans. In the present study, we investigated the immunogenicity of the PAc (361–386) peptide in humans and regulators of induction of the anti-PAc (361–386) peptide IgA antibody (aPPA) in saliva. The PAc (361–386) peptide was confirmed as an ideal peptide antigen for induction of the inhibiting antibody to S. mutans in 151 healthy human subjects (36·6 ± 12·6 years old) by quantitative analyses of oral bacteria and ELISA, as the aPPA titre in human saliva decreased significantly in an age-dependent manner. Homozygous DRB1*0405 and 1502, and heterozygous DRB1*0405/1502 showed a negative association with production of aPPA and tended to reduce the number of total streptococci in saliva. In contrast, the DRB1*1501 allele was significantly correlated with a high level of induction of the antibodies, and also tended to reduce lactobacilli and mutans streptococci. Further, peptide immunogenicity was confirmed in NOD-SCID mice grafted with human peripheral blood mononuclear cells. Our results indicate that the interplay between regulators such as age, DRB1 genotype, cytokines, and peptide immunogenicity may provide a potential means for developing a vaccine useful for the prevention of dental caries as well as their diagnosis.

We demonstrate a thin, selectively lateral-etched, AlIn(Ga)As tunnel-junction (TJ) layer as a current and optical confinement aperture in the InP-based long-wavelength vertical cavity surface-emitting lasers (VCSELs). A high etch selectivity was demonstrated by etching the aperture a distance of several microns without affecting the surrounding InP etch-resistant layer. Edgeemitting lasers enclosing the TJ aperture showed high injection efficiency and low current spreading underneath the aperature. Single-mode continuous-wave operation of a 1.55-μm VCSEL was demonstrated successfully with a room-temperature differential efficiency of 21% using a 6-μm-wide TJ aperature.

Non-potable urban water reuse is Japan's main water reuse practice, which includes water for environmental uses, in-stream flow augmentation, toilet flushing, and industrial reuse. On-site water recycling systems reclaim wastewater on site as well as harvest rainwater in one or more large buildings and distributing the reclaimed water within the buildings for non-potable reuse. Based on our survey conducted in 1999 on current status of on-site water recycling systems in 23 wards of the Tokyo Metropolitan Government District, the following findings are reported in this paper: (1) on the average, 61% of non-potable water demand is met by reclaimed water, and the deficit is made up by tap water from city water supply, (2) biological treatment or ultrafiltration processes can provide reliable treatment and suitable water quality. Some technical problems such as odor from on-site treatment facilities have occurred in a few buildings, (3) there has been no serious accident involving human health by accidentally ingesting reclaimed water, and (4) there is a scale merit in the construction cost of on-site water recycling systems. An on-site wastewater recycling system larger than 100 m3/d is more economically justifiable when compared to a conventional domestic water supply system. An on-site water recycling system can provide an effective, safe, and economical urban water resource for non-potable water reuse applications.

400-nm-band GaN-based laser diodes (LDs) operating with a kink-free output power of over 100 mW and having a low aspect ratio of 2.3 have been successfully fabricated for the first time. A new ridge structure, in which the outside of the ridge is covered with a stacked layer of Si on SiO/sub 2/ and the ridge width is as narrow as 1.5 /spl mu/m, is applied to realize high kink-free output power with a wide beam divergence angle parallel to the junction plane. A new layer structure around the active layer is demonstrated to be quite effective for obtaining a narrow beam divergence angle perpendicular to the junction plane, maintaining low threshold current. Ten LDs with low aspect ratio have been operated stably for over 1000 h under 30-mW continuous-wave operation at 60/spl deg/C. Relative intensity noise measured under optical feedback with high-frequency modulation is as low as -125 dB/Hz. These results indicate that this LD is suitable for next-generation high-density optical storage systems.

1. The effects of Rho-kinase inhibitor, fasudil, and of a more specific Rho-kinase inhibitor, hydroxyfasudil, on pacing-induced myocardial ischaemia were determined in anaesthetized open-chest dogs. 2. The dogs were subjected to left anterior descending coronary artery (LAD) stenosis producing a sufficient ischaemia as measured by ST-segment depression on electrocardiograms only when the hearts were paced 60 beats min(-1) above the baseline. After a recovery (nonpacing) period, drugs or saline were infused intravenously over 30 min. The animals were again subjected to 5 min of pacing 25 min after the initiation of the treatment. 3. Hydroxyfasudil (0.1 and 0.3 mg kg(-1)) and fasudil (0.3 mg kg(-1)) suppressed the ST-segment depression. Hydroxyfasudil and fasudil also increased the regional blood flow of the LAD perfused endomyocardium region in the canine model of effort angina. 4. To determine the flow profile for hydroxyfasudil in dogs, blood flow in three vascular beds was measured. Hydroxyfasudil (0.3 mg kg(-1) for 30 min) significantly increased coronary blood flow and vertebral blood flow, without significantly changing the femoral blood flow. 5. Hydroxyfasudil had no inotropic or chronotropic effect on the isolated hearts of guinea-pigs. Hydroxyfasudil (2 mg kg(-1) for 20 min) did not affect the PR or QTc interval in anaesthetized dogs. 6. Inhibition of Rho-kinase appears to protect myocardium subjected to pacing-induced ischaemia through the increase in the regional myocardial blood flow. Hydroxyfasudil may be categorized as a novel type of anti-anginal drug, without any inotropic or chronotropic effects.

Objective: We recently demonstrated that Rho-kinase/ROK/ROCK is functionally upregulated at the arteriosclerotic coronary lesions and plays a key role for coronary vasospastic responses in our porcine model with interleukin (IL)-1β. In the present study, we tested our hypothesis that Rho-kinase is involved in the pathogenesis of coronary arteriosclerosis per se in our porcine model. Methods: Segments of the left porcine coronary artery were chronically treated from the adventitia with IL-1β. Two weeks after the procedure, coronary stenotic lesions with constrictive remodeling and vasospastic response to serotonin were noted at the IL-1β-treated site, as previously reported. Then, animals were randomly divided into two groups; one group was treated with fasudil for 8 weeks followed by 1 or 4 weeks of washout period and another group served as a control. After oral absorption, fasudil is metabolized to hydroxyfasudil that is a specific inhibitor of Rho-kinase. Results: In the fasudil group, coronary stenosis and vasospastic response were progressively reduced in vivo, while the coronary hyperreactivity was abolished both in vivo and in vitro. Furthermore, Western blot analysis showed that in the fasudil group, the Rho-kinase activity (as evaluated by the extent of phosphorylation of myosin binding subunit of myosin phosphatase, one of the major substrates of Rho-kinase) was significantly reduced, while histological examination demonstrated a marked regression of the coronary constrictive remodeling. Conclusions: These results indicate that Rho-kinase is substantially involved in constrictive remodeling and vasospastic activity of the arteriosclerotic coronary artery, both of which could be reversed by long-term inhibition of the molecule in vivo. Thus, Rho-kinase may be regarded as a novel therapeutic target for arteriosclerotic vascular disease.

An elevated level of adenosine deaminase (ADA) in pleural liquid has been considered as a supplemental diagnostic marker for tuberculous pleurisy. However, this is complicated by false-positives and -negatives. Recently, it has been revealed that various cytokines are intimately involved in the pathognomonic physiology of tuberculosis. In this study, interleukin-8 (IL-8), tumour necrosis factor alpha (TNFalpha) and interferon gamma (IFNgamma) were compared with ADA in pleural liquid of patients with inflammatory (21 cases), malignant (28 cases) and tuberculous (21 cases) disease. The pleural ADA, IL-8, TNFalpha and IFNgamma levels in the tuberculous group were higher than in the other three groups. Analysis of receiver operating characteristic (ROC) curves, to evaluate the utility of the various parameters, demonstrates values for the area under the curve (AUC) of 0.770, 0.875, 0.892 and 0.987, respectively for IL-8, TNFalpha, ADA and IFNgamma. No false-positives were encountered with IFNgamma and only one case with a small volume of pleural liquid was a false-negative. This indicates that IFNgamma is a very reliable marker of tuberculous pleurisy.

A YBCO coated conductor is expected to be a high performance superconductor. To design applied superconducting machines with YBCO conductors, evaluation of not only the superconducting property but also the mechanical property is very important. In particular, the performance against fatigue cycles should be investigated for practical use of the machines. Hence, we measured degradation of YBCO conductors due to bending strain including fatigue. First, we show dependence of the bending strain on critical currents of the conductor. And next, we give the bending strain to the conductor and then release the strain to zero to estimate whether or not the critical currents changes before and after the bending. This test is so called the reversible/irreversible property test. Finally, we show the dependence of the critical currents of the conductor on repeated bending cycles, namely the fatigue test.

Phosphate binders that contain aluminum or calcium are frequently prescribed to treat hyperphosphatemia in patients with end-stage renal disease (ESRD), but an accumulation of aluminum can lead to encephalopathy, aluminum-related bone disease (ARBD) such as osteomalacia, anaemia, and resistance to erythropoietin, and calcium accumulation can lead to hypercalcaemia. High phosphate concentrations are reduced in vitro and in vivo by a phosphate adsorption pill, which is synthesized by hydrolyzing ferrous sulfate in the presence of saccharides, to form an iron (III)-saccharide complex that is acid resistant and binds phosphate greater than iron (III) hydroxide alone. Under in vitro conditions, containing 3.26 mg P/dL, the iron (III)-sucrose complex showed the highest phosphate adsorption capacity at pH 2 with artificial gastric juice, 58.9 mg P/g binder. For the 7 day in vivo study, 0% (Group 1), 1% (Group 2), 4% (Group 3), and 8% (Group 4) iron (III)-sucrose complex was admixed into the rodent chow by weight and fed to 15 male Wistar rats. The weight and volume of the feces and urine, and the calcium, iron, and phosphorus excretions in the feces and urine samples were monitored for any signs of irregularity. Total urine outflow was collected during a 24-h period to determine the amount of phosphate recovered, which indicates the ability of the phosphate binder to reduce gastrointestinal phosphate absorption. The fecal iron excretion was significantly effected by the amount of binder ingested throughout the study for Group 2 (p0.001), Group 3 (p0.01), and Group 4 (p0.001). The urinary calcium excretion (mg/rat/24-h) significantly increased by the 7th day for Group 2 (p0.05) and Group 4 (p0.01) in comparison to the control. Finally, after 7 days, there was a significant drop in the urinary phosphorus levels (mg P/rat/24-h) in a dose dependent manner for Group 2: from 7.82 +/- 1.46 to 1.98 +/- 0.10 mg P/rat/24-h (102 mg P/dL/24-h; p0.05); Group 3: from 6.70 +/- 1.14 to 0.16 +/- 0.09 mg P/rat/24-h (6.0 mg P/dL/24-h; p0.01); and Group 4: from 8.25 +/- 0.67 to 0.04 +/- 0.01 mg P/rat/24-h (0.9 mg P/dL/24-h; p0.01). The results show that this new adsorbent might provide an alternative to conventional aluminum and calcium containing phosphate-binding agents for combating hyperphosphataemia.

Forty-two patients with cutaneous T-cell lymphoma, including 31 with exfoliative erythroderma or Sezary syndrome and 11 with mycosis fungoides, were studied for the occurrence of staphylococcal infection. Thirty-two of 42 (76%) had a positive staphylococcal culture from skin or blood. One half of the patients with positive cultures grew Staphylococcus aureus. This group included 11 with Sezary syndrome and 5 with rapidly enlarging mycosis fungoides plaques or tumors. All of the S aureus carried enterotoxin genes. Surprisingly, 6 of 16 strains were the same toxic shock toxin-1 (TSST-1)-positive clone, designated electrophoretic type (ET)-41. Analysis of the T-cell receptor Vβ repertoire in 14 CTCL patients found that only 4 had the expected monoclonal expansion of a specific Vβ gene, whereas 10 had oligoclonal or polyclonal expansion of several Vβ families. All patients with TSST-1+S aureus had overexpansion of Vβ 2 in blood and/or skin lesions. These studies show that S aureus containing superantigen enterotoxins are commonly found in patients with CTCL, especially individuals with erythroderma where they could exacerbate and/or perpetuate stimulate chronic T-cell expansion and cutaneous inflammation. Attention to toxigenic S aureus in CTCL patients would be expected to improve the quality of care and outcome of this patient population.

We have realized metal-coated semiconductor nanostructures for a stable and efficient single-photon source (SPS) and demonstrated improved single-photon extraction efficiency by the selection of metals and nanostructures. We demonstrate with finite-difference time-domain (FDTD) simulations that inclination of a pillar sidewall, which changes the structure to a nanocone, is effective in improving the photon extraction efficiency. We demonstrate how such nanocone structures with inclined sidewalls are fabricated with reactive ion etching. With the optimized design, a photon extraction efficiency to outer airside as high as similar to 97% generated from a quantum dot in a nanocone structure is simulated, which is the important step in realizing SPS on-demand operations. We have also examined the direct contact of such a metal-embedded nanocone structure with a single-mode fiber facet as a simple and practical method for preparing fiber-coupled SPS and demonstrated practical coupling efficiencies of similar to 16% with FDTD simulation.

Phosphatidylinositol 3-kinase (PI-3 kinase) is implicated in the regulation of diverse cellular processes, including insulin-stimulated glucose transport. PI-3 kinase is composed of a 110-kDa catalytic subunit and an 85-kDa regulatory subunit. Here, we describe p55PIK, a new regulatory subunit that was isolated by screening expression libraries with tyrosine-phosphorylated insulin receptor substrate 1 (IRS-1). p55PIK is composed of a unique 30-residue NH2 terminus followed by a proline-rich motif and two Src homology 2 (SH2) domains with significant sequence identify to those in p85. p55PIK mRNA is expressed early during development, remains abundant in adult mouse brain and testis tissue, and is detectable in adult adipocytes and heart and kidney tissues. p55PIK forms a stable complex with p110, and it associates with IRS-1 during insulin stimulation. Moreover, the activated insulin receptor phosphorylates p55PIK in Sf9 cells, and insulin stimulates p55PIK phosphorylation in CHOIR/p55PIK cells. The unique features of p55PIK suggest that it is important in receptor signaling.

The activity of a free N-acetylneuraminic acid (Neu5Ac)-hydroxylating enzyme which converted Neu5Ac into N-glycolyl-neuraminic acid (Neu5Gc) was demonstrated in the soluble fraction of pig mandibular gland. The hydroxylation was possible only with NADPH as the electron donor. The apparent Km was 4.5 mM Neu5Ac. At 0.5 mM monovalent cations had no effect on the hydroxylation of Neu5Ac whereas bivalent cations gave varied inhibition capacities ranging from 14 to 75%. EDTA gave a time-dependent enhancement of activity. It was concluded that the enzyme does not require an exogenously added inorganic cofactor. Results from salt fractionation of the soluble fraction and the use of inhibitors such as mercurials suggested that the hydroxylation of Neu5Ac to Neu5Gc may involve other, as yet unknown, component(s) and the possibility of electrons donated by NADPH being transferred to activated molecular oxygen (second substrate). We propose to name this enzyme N-acetyl-neuraminic acid hydroxylase.

The interband-resonant light modulation by the intersubband-resonant light in selectively n-doped quantum wells is investigated. The modulation efficiency depends greatly on the degree of nonlinear optical coupling between the interband and intersubband-resonant lights. It is shown theoretically and experimentally that the selective n-doping in the barrier layers of the quantum wells is very effective to increase the nonlinear coupling degree and thus the modulation efficiency. The thermal and the hot carrier effects on the modulation are also discussed. >

A method is proposed whereby both contact force exerted by a flexible manipulator and position of end-effector while in contact with a surface are controlled. The authors derive dynamic equations of joint angles, vibrations of flexible links, and contact force by means of Hamilton's principle. On the basis of some assumptions the authors derive the quasi-static equations and design the hybrid position/force controller of the flexible manipulator. A set of experiments for the hybrid control of the flexible manipulator using a force sensor has been carried out. Several experimental results are shown. >

CuMoO${}_{4}$ is a triclinic quantum magnet based on $S=1/2$ moments at the Cu${}^{2+}$ site. It has recently attracted interest due to the remarkable changes in its chromic and volumetric properties at high temperatures and in its magnetic properties at low temperatures. This material exhibits a first-order structural phase transition at ${T}_{\mathrm{C}}$ $\ensuremath{\sim}$ 190 K as well as a magnetic phase transition at ${T}_{\mathrm{N}}$ $\ensuremath{\sim}$ 1.75 K. We report low-temperature heat capacity measurements as well as extensive elastic and inelastic neutron scattering measurements on powder samples taken above and below ${T}_{\mathrm{N}}$. We observe neutron diffraction consistent with a simple (1/2, 0, 0) antiferromagnetic structure indicating a doubling of the $a$-axis periodicity below ${T}_{\mathrm{N}}$. In addition, inelastic neutron scattering above a spin gap of $\ensuremath{\sim}$2.3 meV is consistent with triplet excitations out of paired $S=1/2$ moments which form singlet dimers. Low-lying spin wave excitations are also observed and these originate from ordered $S=1/2$ moments below ${T}_{\mathrm{N}}$. Taken together these measurements show the ground state of CuMoO${}_{4}$ to display both nonmagnetic singlets and ferromagnetically coupled spins coexisting within an antiferromagnetic structure below ${T}_{\mathrm{N}}$ $\ensuremath{\sim}$ 1.75 K.

In this paper, a method is proposed whereby both contact force exerted by a flexible manipulator and position of end-effector while in contact with a surface are controlled. We derive dynamic equations of joint angles, vibration of the flexible links, and contact force by means of Hamilton's principle. On the basis of some assumptions we derive the quasi-static equations and design the hybrid position/force controller of the flexible manipulator. A set of experiments for the hybrid control of the flexible manipulator using a force sensor has been carried out. Several experimental results are shown

Early pancreatic cancer is small and limited to the pancreas. In contrast, small pancreatic cancer may include peripancreatic vasculature or metastasis involvement. This study evaluates images of early pancreatic cancer on multidetector CT (MDCT) using contrast-enhanced multiphasic imaging, and post-processed pancreatic duct images. CT findings and pathological features were analysed in eight patients with early pancreatic cancer. Pathological evaluation included location, size and histological grading of the tumour. MDCT evaluation covered the maximum diameter of the main pancreatic duct (MPD), stenosis or obstruction of the MPD, loss of normal lobar texture and associated pancreatitis. Attenuation differences between normal pancreatic parenchyma and the tumour (AD–PT) were also measured. Focal stenosis or obstruction of the MPD with dilatation of the distal MPD was demonstrated in all patients. Associated pancreatitis occurred in six patients with tumours measuring 12 mm or greater. Loss of normal lobar texture was recognised in four cases with the tumour measuring 14 mm or greater. Statistically, low-attenuated lesions and high-attenuated lesions differed with respect to the tumour size (p