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BackgroundGenome-wide association studies (GWASs) have identified 29 disease-associated single nucleotide polymorphisms (SNPs) for systemic sclerosis (SSc) in non-human leukocyte antigen (HLA) regions (1-7). While these GWASs have clarified genetic architectures of SSc, study subjects were mainly Caucasians limiting application of the findings to Asians.ObjectivesThe study was conducted to identify novel causal variants for SSc specific to Japanese subjects as well as those shared with European population. We also aimed to clarify mechanistic effects of the variants on pathogenesis of SSc.MethodsA total of 114,108 subjects comprising 1,499 cases and 112,609 controls were enrolled in the two-staged study leading to the ever-largest Asian GWAS for SSc. After applying a strict quality control both for genotype and samples, imputation was conducted using the reference panel of the phase 3v5 1,000 genome project data combined with a high-depth whole-genome sequence data of 3,256 Japanese subjects. We conducted logistic regression analyses and also combined the Japanese GWAS results with those of Europeans (6) by an inverse-variance fixed-effect model. Polygenicity and enrichment of functional annotations were evaluated by linkage disequilibrium score regression (LDSC), Haploreg and IMPACT programs. We also constructed polygenic risk score (PRS) to predict SSc development.ResultsWe identified three (FCRLA-FCGR, TNFAIP3, PLD4) and four (EOMES, ESR1, SLC12A5, TPI1P2) novel loci in Japanese GWAS and a trans-population meta-analysis, respectively. One of Japanese novel risk SNPs, rs6697139, located within FCGR gene clusters had a strong effect size (OR 2.05, P=4.9×10-11). We also found the complete LD variant, rs10917688, was positioned in cis-regulatory element and binding motif for an immunomodulatory transcription factor IRF8 in B cells, another genome-wide significant locus in our trans-ethnic meta-analysis and the previous European GWAS. Notably, the association of risk allele of rs10917688 was significant only in the presence of the risk allele of the IRF8. Intriguingly, rs10917688 was annotated as one enhancer-related histone marks, H3K4me1, in B cells, implying that FCGR gene(s) in B cells may play an important role in the pathogenesis of SSc. Furhtermore, significant heritability enrichment of active histone marks and a transcription factor C-Myc were found in B cells both in European and Japanese populations by LDSC and IMPACT, highlighting a possibility of a shared disease mechanism where abnormal B-cell activation may be one of the key drivers for the disease development. Finally, PRS using effects sizes of European GWAS moderately fit in the development of Japanese SSc (AUC 0.593), paving a path to personalized medicine for SSc.ConclusionOur study identified seven novel susceptibility loci in SSc. Downstream analyses highlighted a novel disease mechanism of SSc where an interactive role of FCGR gene(s) and IRF8 may accelerate the disease development and B cells may play a key role on the pathogenesis of SSc.References[1]F. C. Arnett et al. Ann Rheum Dis, 2010.[2]T. R. Radstake et al. Nat Genet, 2010.[3]Y. Allanore et al. PLoS Genet, 2011.[4]O. Gorlova et al. PLoS Genet, 2011.[5]C. Terao et al. Ann Rheum Dis, 2017.[6]E. López-Isac et al. Nat Commun, 2019.[7]W. Pu et al. J Invest Dermatol, 2021.Disclosure of InterestsNone declared

A hard X-ray polarimeter with CdTe detectors has been developed for measurement of the degree of X-ray polarization at synchrotron radiation facilities. It utilizes 90° Compton scattering from the low Z targets. Measurements were performed at both facilities of the beamline BL38B1 in SPring-8 and the beamline BL14A in KEK-PF. The degrees of X-ray polarization for 20 keV X-rays are 99% and 82% at the BL38B1 in SPring-8 and BL14A in KEK-PF, respectively. The polarization degrees in the energy range of 15 and 40 keV correspond to 99.6±0.2% and 96.1±0.2% at the beamline BL38B1 in SPring-8. The analyzing power of the polarimeter was estimated by the Monte Carlo simulation with EGS4. The synchrotron radiation facilities provide highly polarized X-ray beams at energies above 15 keV.

The performance of the optical imaging capillary gas proportional counter (CGPC) was investigated using polarized X-rays with an energy of 15 keV at SPring-8. The CGPC with a fill gas of Ar+8% CH 4 +2% TMA at 1 atm was operated at a gas gain of 15 000. The CGPC was irradiated by a polarized X-ray beam in the center region using a slit of 300 μm×300 μm. Images of single photoelectron tracks were obtained by an image-intensified CCD camera combined with the CGPC through a lens system. The average distance between the starting point and the barycenter for single photoelectron tracks was 1.1 mm. The angular distribution is obtained from the directions of the lines connected between the starting point and the barycenter for each image of the photoelectron tracks. From a least-squares fitting, the modulation factor was 25.1±2.0% for the X-rays with a polarization degree of 99%.

We show the key results of our 4-year experience with sirolimus in kidney transplant patients and in nontransplanted patients undergoing coronary angioplasty. Methods Recipients of one-haplotype living-related kidney allografts were randomized to receive sirolimus (2 mg/d, n = 35) or azathioprine (2 mg/kg per day, n = 35). Recipients of fully mismatched living kidney allografts ( n = 55) received sirolimus (2 mg/day). High-risk recipients of black ethnicity ( n = 68) were randomized to target whole-blood trough sirolimus concentrations between 8 and 12 ng/mL or 15 to 20 ng/mL. All kidney transplant patients received cyclosporine and prednisone. Sirolimus/cyclosporine pharmacokinetic studies were performed in 40 patients receiving 2 mg ( n = 20) or 5 mg ( n = 20) of sirolimus 7 days after transplantation. In the coronary intervention study, 12 patients at high risk for in-stent restenosis received sirolimus for 28 days after angioplasty. Results The incidence of biopsy-confirmed acute rejection was 11.4% in recipients of one-haplotype living-related kidney allografts, 16.4% in recipients of fully mismatched living kidney allografts, and 15% (8 to 12 ng/mL) and 4% (15 to 20 ng/mL) in high-risk recipients of black ethnicity. Cyclosporine exposure was higher after morning administration compared to evening administration. There were poor correlations between sirolimus and cyclosporine exposures. The 4-month follow-up angiography revealed no restenosis (stenosis diameter > 50%), a late loss of 0.56 ± 0.40 mm, and a loss index of 0.33 ± 0.30. The follow-up 3D-intravascular ultrasound restudy showed an in-stent relative volumetric obstruction of 9.9 ± 5.5%. Sirolimus in highly effective in preventing kidney allograft acute rejection and in-stent coronary restenosis.

application/pdf, A probe wave system was constructed for studying the excitation of the Alfvén ion cyclotron (AIC) modes in the anchor cell of the GAMMA 10 tandem mirror. In the central cell, the AIC modes are spontaneously excited as axial eigenmodes due to the strong temperature anisotropy. In the anchor cell, the AIC modes were not observed though the anisotropy is the same as in the central cell. The axial profiles of the magnetic field strength and plasma parameters in the anchor cell are different from those in the central cell. Eigenmodes are excited externally in the AIC frequency range by injecting probe waves. This suggests the AIC modes are unstable in the anchor cell and grow to the detectable level when boundary conditions are realized.

In the limited regions of operation of the GAMMA10 tandem mirror, a saturation or a reduction of the stored energy in the central cell is sometimes observed. By using electrostatic and magnetic probes, the low frequency (

Validity of averaged minimum- B configuration on Magnetohydrodynamics (MHD) stability of the GAMMA10 tandem mirror are studied in the ion cyclotron range of frequency (ICRF)-heated, hot ion mode plasma. It has been observed that the plasma can not be sustained mostly owing to the flute interchange mode when the high power ICRF is applied for the central cell ion heating. As the ratio of the central cell beta to the anchor cell beta increases, the amplitude of the flute interchange mode increases. The anchor cell plasma is also sustained by the another ICRF source in the central cell. The flute type MHD instability in GAMMA10 is well controlled by the phased ICRF antennas in the central cell.

Cellular expression of cytosolic phospholipase A2 (cPLA2) was investigated in the rat ovary in different endocrine states. Its mRNA expression was detected by RT-PCR. The immunohistochemistry identified an intense signal for cPLA2 in oocytes. Granulosa and thecal cells in growing follicles were negative, but turned positive during the periovulatory period, whereas those in atretic follicles were highly immunoreactive. The immunoreactive signal was modest in newly formed corpora lutea (CL) but intensified in functionally and morphologically regressing CL. These results show a broad but specific distribution of cPLA2 in ovarian cell types, and suggest its role in ovulation, CL regulation and apoptotic processes.

Some cases of human papillomavirus (HPV) type 56 infection in Bowen disease have been reported. However, the incidence and clinical characteristics are still unclear.To clarify the prevalence of HPV type 56-positive Bowen disease in our department and to characterize the clinical manifestations.Sixty-eight specimens of Bowen disease were examined by polymerase chain reaction using HPV consensus primers, and the amplified products were subjected to DNA sequence analyses. Moreover, positive samples were investigated by in situ hybridization. These findings were used to clarify the clinical characteristics of HPV-positive Bowen disease.Eight out of 68 specimens (12%) of Bowen disease were HPV-positive, of which six specimens were HPV type 56-positive. The HPV type 56-positive lesions were characterized by a longitudinal melanonychia or a deeply pigmented keratotic lesion. The remaining two specimens were genital Bowen disease in which HPV type 16 was detected. In situ hybridization demonstrated the positive cells in the upper layer of epidermis. The HPV type 56 detected in the samples of longitudinal melanonychia can be divided into at least into two types.This study determined the prevalence of HPV type 56-positive Bowen disease. Longitudinal melanonychia is the most characteristic manifestation of HPV type 56-associated Bowen disease.

Spontaneous vehicular networks formed by vehicles contribute to safe and comfortable driving by disseminating vehicular movement information. Inter-vehicle communication protocols have been proposed that can provide indirect communications by relaying packets. Although the relay expands the area over which packets can deliver, it generates new communication traffic, hence existing protocols have some mechanism to reduce this traffic, for example the selection of a minimum set of relaying vehicles. However, communication delays increase due to the overhead of the mechanism when the numbers of vehicles increase. In this paper, we propose a relay control protocol for the data dissemination of Spontaneous Vehicular Networks. The protocol controls the relay of each packet, on an as-required basis, in order to adapt to various vehicular communication environments. In addition, the protocol reduces communication traffic by avoiding duplicate relays through a duplicate relay detection algorithm. Furthermore, we evaluate the proposed protocol through experiments and compare it with one of the existing protocols.

Wireless sensor network monitoring is important for network maintenance, since it keeps the observer aware of node failures, resource depletion etc. Since communication overheads increase if the sink collects data individually from all sensor nodes, in-network data aggregation methods have been proposed which reduce the overheads. They form a routing tree and data follows up from the edge of the tree to the sink. However, in the event of heavy packet loss, the error margin of the collected data received by the sink grows. Furthermore, when the assumed hop count of the edge of the tree is smaller than the actual count, data can not be followed up from the edge. For the reasons mentioned above, observers find it problematic to assess the state of the network, since the error margin increases as the accuracy of the collected data falls. In this paper, we propose a new in-network aggregation method for sensor network monitoring. The method provides fault tolerance for packet loss by forming a directed acyclic graph (DAG), which allows a node to have multiple parent nodes. In addition, the method can ensure correct data transmission timing, according to the actual hop count of the edge of the DAG. Furthermore, we evaluated the proposed method in comparison with the existing methods, from the perspective of the error margin of the collected data.

An X-band klystron modulator using a new type Blumlein and a magnetic switch was developed for the Japan Linear Collider (JLC) project. The specifications of this modulator are an output voltage of 600kV, a pulse length (flat-top) longer than 100ns, a pulse rise time less than 100ns and a rather high output impedance of several hundred ohms. To realize a compact modulator satisfying these specifications, helically wound conductors were used for the inner and middle conductors of the Blumlein. Details of the Blumlein with helical conductors and results of the performance tests are described. And it was confirmed that a pulse with flat-top length longer than 100ns can be generated by a 1m long Blumlein for 650/spl Omega/ impedance load.

The purpose of this paper is to report on success in FIB editing devices with interconnects of copper, SiO/sub 2/ and low-k dielectrics. Our approach is based on using a FIB activated chemistry to decrease decomposition of dielectric as well as bind-up redeposited copper in a non-conducting state.

In this paper, we propose an energy-efficient address allocation method for the event-driven sensor network, and implement and evaluate the proposed method. The proposed method allocates a temporary address only to a sensor node which detects an event, on an on-demand basis. By performing simulation studies, we evaluated the proposed method and compared it with one of the existing methods from the perspective of the number of control messages for the address allocation. The results show that the number of control messages of the proposed method is small compared to that of the existing methods. We also evaluated the processing time overhead of the proposed method using the implemented system. Although the proposed method has little extra overhead, the results show the processing time is short enough for practical use.

Towards the wide acceptance of ubiquitous networking, practical and deployable ubiquitous applications must be provided in a concrete and easily understandable form to end-users. We designed and implemented ubiquitous nodes, KDDI Ubiquitous Bit (kubit). The highest priority was given to application-oriented design and ease of deployment in a typical home network environment. The kubit quickly detects anything suspicious with built-in sensors, and sends notification of the event via e-mail containing an image to be displayed on a PC or mobile phone, as well as controlling the existing home appliances via a PC or mobile phone or led by the event.

Multi hop wireless ad hoc networks can be formed by a group of wireless nodes without requiring the use of a preexisting infrastructure. However such an ad hoc network environment is hard to administer, so applications cannot assume they know which services exist and where they are hosted. A service discovery that provides automatic discovery of desired services to the applications is particularly important to save the user from the trouble of configuring tasks and has the advantage of a full range of provided services. In this paper, we propose a new service discovery method for multi hop wireless ad hoc networks. The method provides an efficient method of service discovery for increasing the number of discoverable services. We evaluate the proposed method through a simulation study and compare it with the existing method. Results show that the proposed method achieves better performance in terms of the number of discoverable services, while the number of control messages and response time for discovering the services are almost the same as the existing method.

The current-fed high-power-factor converters (buck and buck-boost converters) have several advantages, such as no lower-limit of the output-voltage control range and no rush-current of the input-current. However, the single-phase current-fed high-power-factor converter with PWM (pulse width modulation) produces undesirable lower order harmonics in the input-current. Thus, the PWM requires a bulky and costly inductor connected in the DC-side of the current-fed converter to reduce the DC-inductor-current ripples. To overcome the problem, the authors have proposed PSM (pulse-space-modulation). This paper describes a comparison of the characteristics (THD (total harmonic distortion of the input-current), the power factor and reducing DC-inductor's inductance) between buck and buck-boost high-power-factor converters applying PSM. The buck-boost converter has many advantages over the buck converter in the input current waveform, power factor and reducing DC-inductor's inductance. To illustrate the validity of the theory, experimental results obtained from a 1.2 kW setup and computer simulation results are shown.

The Asynchronous Transfer Mode (ATM) has been standardized and widely accepted as a technique to support future B-ISDN networks. In ATM networks, traffic control design becomes an important challenge, because of the diverse services support and the need for efficient network resource engineering. Two important functions for traffic control in ATM networks are policing and routing. The goal of these two functions is to guarantee the required quality of service. So far, all studies have treated policing and routing in a separate way. The combination of policing and routing can guarantee a better quality of service and increase the network utilization. Traditional network control strategies are not well suited for high speed networks. Use of intelligent algorithms based on fuzzy logic, neural networks and genetic algorithms can prove to be efficient for traffic control in ATM networks. We propose an intelligent policing-routing mechanism based on fuzzy logic and genetic algorithms. Performance evaluation via simulations shows that the proposed mechanism performs better than conventional policing mechanisms and routing algorithms.

This paper describes a new single-phase buck-boost power factor correction (PFC) converter with output-voltage-ripple-free operation. The rectifier is operated by two modulators which obtain PFC and the ripple-free operation, respectively. The modulator controls the buck-boost switch to obtain PFC. On the other hand, another modulator controls squire-value of instantaneous-inductor-current to perform the ripple-free operation. In both modulation, space or time-integral-value of the input and output currents in each modulation period is controlled directly and indirectly, respectively. Thus, modulation errors or distortions of the currents are eliminated even if the DC-inductor-current produces large ripples. The theories and combination technique of the modulators, implementation and experimental results are shown.

The improvement of the quality control in the detection of fluorescent antinuclear antibodies (FANA) have decreased the differences among institutions. However, the positive lower or upper reference limit and the criteria for the determination vary among laboratories. By examining 725 sera from children and 227 sera from healthy adults, we proposed the titers of 160-320 for children and 80-160 for adults as the positive lower limits. The higher positive incidence in the children's sera might be due to some abnormality in the ANA production or the higher sensitivity of the reagents used. The clinical significances of the anti-U1RNP antibody and anticentromere antibody (ACA) in ANA have been described. The anti-U1RNP antibody, present in only MCTD and related disorders, might play some role in the development of Raynaud's phenomenon and symptoms in a case of neonatal lupus erythematosus. ACA was detected in sera not only of CREST syndrome patients but also of PBC patients. The functions and molecular structures of nuclear antigens have recently been extensively investigated. However, the pathogenetic significance of most of the ANA and the mechanism of their production have not been clarified yet.

The Alfvén ion cyclotron (AIC) mode is spontaneously excited due to a temperature anisotropy in the ion cyclotron range of frequency (ICRF) heating experiments in the GAMMA10 tandem mirror. The behavior of the AIC mode is studied when the second harmonic electron cyclotron resonance heating is applied additionally. It is confirmed experimentally, that the excitation of the AIC mode is determined solely by the ion pressure and the ion pressure distribution.

Experiments have been conducted on high voltage dc breakdown characteristics with large oil gaps of typical electrode setups, which are plane to plane and cylinder to plane. These have been confirmed in a voltage-range up to 800 kV and in gap length up to 307 mm.