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Takuya Samukawa,1,* Koichiro Matsumoto,2,* Go Tsukuya,1 Chihaya Koriyama,3 Satoru Fukuyama,2 Akifumi Uchida,1 Keiko Mizuno,1 Hironori Miyahara,4 Yutaka Kiyohara,5 Toshiharu Ninomiya,6 Hiromasa Inoue1 1Department of Pulmonary Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, Kagoshima, 2Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University, Fukuoka, 3Department of Epidemiology and Preventive Medicine, Graduate School of Medical and Dental Sciences, Kagoshima University, 4Kagoshima Kouseiren Medical Health Care Center, Kagoshima, 5Hisayama Research Institute for Lifestyle Diseases, 6Department of Epidemiology and Public Health, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan *These authors contributed equally to this work Background: The use of a simple screening questionnaire to detect persistent airflow obstruction (AO) in COPD may facilitate the early, accurate diagnosis of COPD in general practice settings. Objective: This study developed an original persistent AO questionnaire for screening individuals with COPD in a general Japanese population. Methods: A working group was established to generate initial draft questionnaire items about COPD. Eligible subjects aged 40 and older living in Japan were solicited to participate in a health checkup from 2014 to 2015. In study I, 2,338 subjects who fully completed the initial draft questionnaire and who had valid spirometry measurements were statistically analyzed to determine the final questionnaire items as a COPD screening questionnaire (COPD-Q). Persistent AO was defined as a post-bronchodilator FEV1/FVC

Yasuharu Nakashima,1 Masakazu Kondo,2 Hisaaki Miyahara,3 Yukihide Iwamoto11Department of Orthopaedic Surgery, Kyushu University, Fukuoka, Japan; 2Kondo Clinic of Rheumatology and Orthopaedic Surgery, Fukuoka, Japan; 3Department of Orthopaedic Surgery and Rheumatology, Clinical Research Institute, National Hospital Organization Kyushu Medical Center, Fukuoka, JapanAbstract: Rheumatoid arthritis (RA) is a chronic, progressive, inflammatory disease associated with joint destruction. Tocilizumab (TCZ) is a humanized monoclonal anti-interleukin-6 receptor antibody that was initially developed for use as an intravenous (IV) infusion. Previous studies have shown that TCZ-IV is an important treatment option in patients with moderate-to-severe RA. A subcutaneous (SC) formulation of 162 mg TCZ that was recently developed and approved provides an additional treatment option for RA patients. In the present review, we provide an update on the efficacy and safety of TCZ-SC, compared with TCZ-IV. The TCZ-SC doses of 162 mg every 2 weeks (q2w) or weekly (qw) were selected based on pharmacokinetic and pharmacodynamic studies. Both TCZ-SC q2w and qw regimens showed equivalent effects to TCZ-IV in most patients; however, the TCZ-SC qw regimen consistently showed a more rapid effect in terms of C-reactive protein normalization. Randomized controlled studies showed that TCZ-SC monotherapy or combined with disease-modifying antirheumatic drugs demonstrated comparable efficacy to TCZ-IV in patients who were both biologic-naïve and refractory to tumor necrosis factor inhibitors. TCZ-SC at both qw and q2w were generally well-tolerated for up to 24 weeks. There was a low rate of withdrawal due to adverse events, and their incidence was comparable with that seen with TCZ-IV. An injection site reaction was seen in approximately 10% of patients who received the subcutaneous formulation. In conclusion, although clinical results are still limited, the currently available evidence suggests that TCZ-SC is a promising treatment for moderate-to-severe RA, both as monotherapy and combination therapy. More data is needed to determine the optimal dosing schedule.Keywords: rheumatoid arthritis, tocilizumab, subcutaneous injection, review

Due to a large number of bursty traffic sources that an ATM network is expected to support, controlling network traffic becomes essential to provide a desirable level of network performance with its users. Admission control and traffic smoothing are among the most promising control techniques for an ATM network. To evaluate the performance of an ATM network when it is subject to admission control or traffic smoothing, we build a discrete-time single-server queueing model where a new call joins the existing calls.In our model. it is assumed that the cell arrivals from a new call follow a general distribution. It is also assumed that the aggregated arrivals of cells from the existing calls form batch arrivals with a general distribution for the batch size and a geometric distribution for the interarrival times of batches. We consider both finite and infinite buffer cases, and analytically obtain the waiting time distribution and cell loss probability for a new call and for existing calls. Our analysis is an exact one. Through numerical examples, we investigate how the network performance depends on the statistics of a new call (burstiness, time that a call stays in active or inactive state, etc.). We also demonstrate the effectiveness of traffic smoothing to reduce network congestion.

The experimental evidence is presented of the topological insulator state in PbBi2Te4. A single surface Dirac cone is observed by angle-resolved photoemission spectroscopy with synchrotron radiation. Topological invariants Z2 are calculated from the ab initio band structure to be 1;(111). The observed two-dimensional isoenergy contours in the bulk energy gap are found to be the largest among the known three-dimensional topological insulators. This opens a pathway to achieving a sufficiently large spin current density in future spintronic devices. [ABSTRACT FROM AUTHOR]

The relationship between solar activity and the global climate is not only an academically interesting problem but also an important subject for human beings. We have found an interesting relation that may be connected with above profound problem. We have analyzed the tree rings that had survived for 391 years in Japan. The tree archive is very important since it includes the period of the Maunder minimum. Quite surprisingly, Fourier analyses of the annual growth rate identified two cycles with periodicities of 12 and 25 years during the Maunder minimum, but no such cycles were found for other time periods. Possible interpretations of this result are presented. [ABSTRACT FROM AUTHOR]

Short-lived radionuclides for positron emission tomography (PET) examinations in medicine are produced mainly using on site small cyclotrons. The operation of the cyclotron generates a significant quantity of neutrons, which will activate the cyclotron and surrounding materials. A new technique is proposed to estimate the neutron fluxes in the cyclotron rooms, in which small bolts in the cyclotron rooms were used as surrogates for neutron detectors. The measurements were carried out at four PET cyclotrons. The induced radioactivity of the bolts was analyzed by gamma-ray spectroscopy and elemental analysis. A gold foil activation method was applied to compare the results. The neutron fluxes in the PET cyclotron rooms were in the range of 105 ~ 106 cm-2 s-1 during 18F production. In the brass bolts, 69mZn, 65Zn, 64Cu, 58Co, and 60Co were detected. In the iron bolts, 56Mn, 54Mn, 59Fe, 60Co, 69Zn, and 65Zn were detected. In the stainless steel bolts, 58Co, 60Co, 56Mn, 54Mn, and 49Fe were detected. Neutron fluxes estimated from the activities of 56Mn agreed well with those by the Au foil method. The feasibility of estimating the neutron fluxes in cyclotron rooms by means of radioactive analysis of bolts in the rooms was proven. [ABSTRACT FROM AUTHOR]

There has been increasing interest in phenomena emerging from relativistic electrons in a solid, which have a potential impact on spintronics and magnetoelectrics. One example is the Rashba effect, which lifts the electron-spin degeneracy as a consequence of spin-orbit interaction under broken inversion symmetry. A high-energy-scale Rashba spin splitting is highly desirable for enhancing the coupling between electron spins and electricity relevant for spintronic functions. Here we describe the finding of a huge spin-orbit interaction effect in a polar semiconductor composed of heavy elements, BiTeI, where the bulk carriers are ruled by large Rashba-like spin splitting. The band splitting and its spin polarization obtained by spin- and angle-resolved photoemission spectroscopy are well in accord with relativistic first-principles calculations, confirming that the spin splitting is indeed derived from bulk atomic configurations. Together with the feasibility of carrier-doping control, the giant-Rashba semiconductor BiTeI possesses excellent potential for application to various spin-dependent electronic functions. [ABSTRACT FROM AUTHOR]

Although linkages between solar activity and the earth's climate have been suggested and the 11-year cycle in solar activity evident in sunspot numbers is the most examined example of periodicity in previous studies, no quantitative evidence indicating a relationship for tropospheric phenomena has been found for a short period. Based on FFT analysis for OLR (Outgoing Longwave Radiation) compared with the F10.7 index, we clearly demonstrate a 27-day variation in the cloud amount in the region of the Western Pacific warm pool, which is only seen in the maximum years of 11-year solar activity. The average spectrum in such years also shows an enhancement in the range of the MJO (Madden-Julian Oscillation) period. Although there exist some explanations for possible mechanisms, the exact cause is unknown. Therefore, the proposed connection between 27-day cloud variation and solar cycle in the WPWP region is still a hypothesis and various kinds of varification based on other meteorological and solar parameters are strongly required. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To investigate safety, pharmacokinetics and pharmacodynamics of albiglutide in Japanese subjects with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: This randomized, single-blind, placebo-controlled study examined four doses/dose schedules of subcutaneously (sc) administered albiglutide: 15 mg weekly, 30 mg weekly, 50 mg biweekly, and 100 mg monthly (cohorts A-D, respectively) in 40 subjects (mean age 54.5 years, mean range of glycosylated hemoglobin [HbA(1c)] 7.1-8.3%), over a 4-week treatment period. MAIN OUTCOME MEASURES: Safety parameters, including adverse events, clinical laboratory tests, vital signs, and 12-lead electrocardiogram; plasma concentrations of albiglutide; and pharmacodynamic parameters, including change from baseline and weighted mean AUC(0-4) in plasma glucose, glucagon, insulin, and C-peptide levels. CLINICAL TRIAL REGISTRATION: NCT00530309. RESULTS: At day 29, mean changes from baseline (vs. placebo) in fasting plasma glucose (FPG) were: cohort A, -1.92 mmol/L; B, -1.98 mmol/L; C, -1.74 mmol/L; D, -0.73 mmol/L; changes in weighted mean glucose AUC(0-4) were: cohort A, -2.86 mmol/L; B, -3.58 mmol/L; C, -2.51 mmol/L; D, -1.44 mmol/L (for FPG and AUC(0-4), all p < or = 0.002 except 100 mg sc monthly, p = NS); changes from baseline HbA(1c) were: cohort A, -0.58%; B, -0.57%; C, -0.63%; and D, -0.51% (all p < 0.03). Albiglutide sc had a median half-life of 5.3 days, plasma apparent systemic clearance of 68.7 mL/h, and apparent volume of distribution of 12.6 L. Incidence of adverse events was low and comparable to sc placebo in all albiglutide treatment arms except 100 mg sc monthly, where gastrointestinal (GI) adverse events were most common. Limitations of this study include the small sample size, short treatment duration, and enrollment of predominantly male subjects. CONCLUSIONS: Weekly and biweekly albiglutide improved glycemic control and were well-tolerated in Japanese subjects with type 2 diabetes mellitus. [ABSTRACT FROM AUTHOR]

Linkages between solar activity and the earth's climate have been suggested in previous studies. The 11-year cycle in solar activity evident in sunspot numbers is the most examined example of periodicity, and it is clearly recognized in variations in the thermal structure and dynamical motion of the stratospheric atmosphere. Also the variations in the stratosphere related to the period of apparent solar rotation have also been suggested; however, for such a short period, no quantitative evidence indicating a relationship to the tropospheric phenomena. We clearly demonstrate a 27-day variation in the cloud amount in the region of the Western Pacific warm pool, which is only seen in the solar maximum years of the 11-year cycle. The average spectrum in solar maximum years also shows an enhancement in the range of MJO period. Long-term variations in the tropospheric phenomena, including the 11-year cycle, are generally investigated based on monthly or even yearly averaged data, but the present results may suggest an alternative possibility: short-period variations could modulate longer periodic phenomena. [ABSTRACT FROM AUTHOR]

Graphite formation should be strictly suppressed for the most abrasion resistant white cast irons, since austenite (γ)+graphite eutectic structure shows lower hardness and selectively wears thus deteriorates the abrasion resistance even though the austenite transform to hard phase such as martensite. On the other hand, a small amount of fine graphite is desired to distribute in rolls for hot steel mills to suppress the scoring. However, strong carbide formers such as Cr, V, Nb have been increasingly added to rolls, in order to crystallise more harder carbides. As γ+carbide eutectic grows, the residual liquid among eutectic cells becomes poor in carbide formers and rich in elements which promote graphite formation. Therefore an appropriate alloy design is essential for the hot steel milling rolls. In this study, the graphite formation mechanisms are discussed for chromium cast iron, high speed steel type cast iron and Ni hard type cast iron. [ABSTRACT FROM AUTHOR]

State of technologies in Japan related to composite casting was reviewed based on the three year survey of Composite Casting Process Sub-Committee in Committee on Foundry Technology (24th) of JSPS. Other than making metal matrix composite, cast-in insertion, bonding and joining of cast materials and other technologies combining different materials by casting process were included. Basic theories and the key technologies are explained, and a number of typical examples of products, on production or on experimental bases, were reported. Overseas literatures were also surveyed. [ABSTRACT FROM AUTHOR]

Wear behaviour was investigated for high volume fraction SiC particulate reinforced aluminum alloy composites by considering the shear stress acting on the specimen and the wear debris formed during sliding wear. The SEM morphology of worn subsurfaces showed that particles are fragmented, mechanically mixed, and then aligned in the wear direction caused by normal and tangential stresses. Wear debris were initially tiny lumps but finally delaminated due to the shear stress. A theoretical wear model was proposed for plastically deformable specimens worn by a rigid non-deformable steel ring by analysing the interspacing of SiC particles and the tangential stress applied to the worn surface. Predictions of this theoretical wear model were in good agreement with experimental results. [ABSTRACT FROM AUTHOR]

The sliding wear behaviours of an unreinforced monolithic Al--Si--Cu alloy and SiC particles reinforced composites containing 5, 13, 38 and 50 vol.-% with diameters of 5⋅5, 11⋅5 and 57 µm were investigated. The results showed that the wear resistance of the composites is much higher than the monolithic alloy, and the larger and the more SiC particles, the higher the enhancement of the wear resistance. Metallographic examinations revealed that the subsurface of worn composites was composed of both fragmented particles and deformed matrix alloy. The depth of the particle fracture zone in the subsurface varied in the range of 20--35 µm at a sliding distance of 1⋅8 km, while the plastic deformation zone of the worn subsurface on monolithic alloy was more than 100 µm. Scanning electron microanalyses of the worn surface, subsurface microstructure and debris suggested that the depth of the particle fracture zone became smaller as the diameter of SiC particles increased. Increasing the hardness and decreasing the applied wear stress changed the debris morphology from flake to very small lumps. [ABSTRACT FROM AUTHOR]

It is true that in all-optical networks, network performance can be improved by wavelength conversion. However, the switching node with wavelength conversion capability is still costly, and the number of such nodes should he limited in the network. In this paper, a performance optimization problem is treated in all-optical networks. We propose a heuristic algorithm to minimize an overall blocking probability by properly allocating a limited number of nodes with wavelength conversion capability. The routing strategy is also considered suitable to the case where the number of wavelength convertible nodes are limited. We validate the minimization level of our heuristic algorithm through numerical examples, and show that our algorithm can properly allocate nodes with conversion and decide routes for performance optimization [ABSTRACT FROM PUBLISHER]

Tolerization of B10.RIII mice (H-2r) with intravenously injected type II collagen (CII) renders the animals resistant to induction of collagen-induced arthritis (CIA). In order to clarify 11-2r- restricted T-cell responses that modulate CIA, we have analysed the T-cell proliferative response of B10.RIII mice against cyanogen bromide (CB) peptides of CII, and detected the strongest response to α(II)-CB10 (CII 552–897). A panel of chemically synthesized overlapping peptide homologues was used to deduce the minimum structure of this determinant which was found to be CII 610–618. A 15-residue synthetic peptide flanking this region. CII 607–621, was found to effectively suppress arthritis when administered as a tolerogen. Collectively, these data identify the structural component within α1(II)-CB10 which is capable of inducing tolerance in BIO.RIII mice. A similar approach to the treatment of autoimmune arthritis, involving the institution of self-tolerance, has potential applicability to human rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Susceptibility to collagen-induced arthritis (CIA), a murine model of autoimmune arthritis, is strongly linked to only two major histocompatibility complex (MHC) haplotypes, H-2q and H-2r. In order to identify the determinants of type II collagen (CII) required to induce arthritis in H-2rbeating mice, B10.RIII mice were immunized with bovine, chick or human CII. Only bovine Cfi induced significant arthritis and autoantibodies. When the major CNBr peptides of bovine collagen were isolated and used for immunization, only mice immunized with CB8, representing CII 403-551, developed arthritis. To identify immunogenic epitope(s) within CB8, a panel of synthetic peptides representing overlapping sequences of the bovine peptide was generated. When each peptide was cultured with T cells from B10.RIII mice immunized with CII, one peptide, representing CII 430-466, contained a major T-cell epitope. By using an in vitro lymphokine production assay, the T-cell epitope was further narrowed to CII 442-456. These findings suggest that a T-cell determinant important for the initiation of arthritis in B10.RIII (H-2r) mice is located within a 15 amino acid sequence, residues 442-456 of bovine CII. [ABSTRACT FROM AUTHOR]