Objective: Iguratimod (

) was newly approved in Japan in 2012. In this retrospective study, we have investigated the efficacy and safety of in patients with rheumatoid arthritis (RA).

Methods: One hundred thirty nine patients were treated with

at our institution during the period of 2012-2014. Among those patients, 109 who were able to continue using for over 12 months were divided into three groups. M−: 44 patients who started due to intolerance to methotrexate (MTX), M+: 25 patients in whom was added because treatment with MTX was unable to control the disease, and +: 40 patients in whom was added because treatment with biological agents was unable to control the disease. The results were assessed by disease activity index, inflammatory reaction, and autoantibody values.

Results: Adverse reactions including exanthema and abdominal pain were observed in 25 patients (18.9%). Nine patients who experienced adverse reactions such as liver damage were able to continue the treatments by reducing the amount of

to 25 mg/day. DAS28-ESR (4) showed a significant improvement, on average from 5.03 at baseline, to 3.62 at six months. C-reactive protein levels decreased from on average from .4 mg/dl to 1.0 mg/dl, respectively. This trend continued for 30 months and was maintained. Matrix metalloproteinase-3 and rheumatoid factor (RF) IgM values also showed significant decreases. At one year, there were obvious improvement rates in the DAS, which was observed in M−, +and M+groups, respectively. Patients with high RF values showed clearer improvements than those with lower values.

Conclusions: Though there is significant value of using methotrexate and biological agents in the treatment of RA, some patients have to discontinue such drugs due to intolerance, lack of efficacy, and adverse reactions. Under these circumstances,

should be considered as an additonal treatment option.

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In order to use the nationwide dense receiver network of the Global Positioning System (GPS) in Japan to contribute to water vapor monitoring and numerical weather prediction, a near real-time (NRT) analysis trial was performed at the Meteorological Research Institute. In this paper, the NRT analysis procedure is described along with some validation results.
In view of the computational load involved in analyzing more than 1,300 GPS stations in Japan, the precise point positioning (PPP) procedure was adopted. The PPP procedure requires accurate information of GPS satellites’ positions and clock offsets. International GNSS Service (IGS) has been routinely providing ultra rapid ephemeris () that includes satellite orbits and clock offsets with latency of about 3 hours. We found the accuracy of satellite clock offsets in was insufficient for the retrieval of precipitable water vapor (PWV) through the PPP procedure. Therefore, we applied correction to the clock using the predicted clock offset at an IGS station “USUD”. The hydrogen maser atomic clock at USUD also had some differences with GPS time. However, we found it could be fitted and predicted by a linear equation for a period of several days.
The resulting satellite clock offsets exhibited some biases toward the IGS final ephemeris, but the time constant biases of satellite clock offsets did not affect the PWV retrieval at all. The retrieved PWV data agreed well with those obtained from radio-sonde observations. The root mean square differences in summer and in winter were around 3.4 mm and 1.6 mm, respectively. The results were comparable with those obtained by preceding studies using the final ephemeris. The Retrieved spatial and temporal variation of PWV in a heavy rainfall case demonstrated the usefulness of the NRT PWV retrieval for weather monitoring. We could capture the water vapor increase that preceded torrential rain.

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Iguratimod (

) is a disease-modifying antirheumatic drug, whose activity is mainly ascribed to the inhibition of NF-kB pathway. Interestingly, we have noticed that the serum uric acid (UA) levels were decreased in 22% of rheumatoid arthritis patients taking . Since there have been no reports of affecting UA, we decided to explore how lowers the serum UA level.

We first examined whether

inhibits the xanthine oxidase (XO) activity. Xanthine and XO were incubated with the drug and the production of UA was measured by absorbance at 290 nm. UA production was not inhibited by . Next, we examined whether or its metabolites inhibit the UA transporters. As M3 and M4 are the major metabolites in the urine, we examined the inhibitory activities of and these metabolites against the major UA transporters, GLUT9 and URAT1, in the xenopus oocytes expression system. and M4 inhibited the URAT1, and their IC₅₀s were 12.61 ± 0.97 μM and 120.07 ± 26.69 μM, respectively. However, the estimated maximal concentrations of these compounds in the proximal tubule were 4 - 7 times lower than the IC₅₀.

In conclusion, UA lowering effect of

is not likely to be explained by its or its metabolite's direct interaction with XO, URAT1, or GLUT9.

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The GPS meteorology has been the driving force behind the near real-time (NRT) GPS analyses during the past few years. High availability of precise near real-time GPS orbits is essential for obtaining reliable solutions in almost all applications. This is especially true when estimating the troposphere parameters. Besides the demand on high accuracy, the orbit products should stand out for their stability in production as well as for their completeness in set of satellites. The most likely candidates for the applicable orbits are products of the International GPS Service (IGS). We will outline, at first, the results of our monitoring activity of the IGS ultra-rapid orbits provided beside their routine usage in Geodetic Observatory Pecny´ (GOP). Thereafter, we will explain our procedure for NRT orbit determination using an efficient technique of combining short orbit arcs into the final orbits over -3 days. Our official orbit results, as well as testing variants of the combination, were evaluated using the IGS final and ultrarapid orbit products. Finally, we will demonstrate the direct application of our orbits in the NRT GPS analyses for sensing the regional and global troposphere.

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In the era of IPv6, since the number of IPv6 addresses rapidly increases and the required speed is more than Giga lookups per second (GLPS), an area-efficient and high-speed IP lookup architecture is desired. This paper shows a parallel index generation unit () for memory-based IPv6 lookup architecture. To reduce the size of memory in the , we use a linear transformation and a row-shift decomposition. A single-memory realization requires O( log k) memory size, where l denotes the length of prefix, while the realization using requires O(kl) memory size, where k denotes the number of prefixes. In IPv6 prefix lookup, since l is at most 64 and k is about 340 K, the drastically reduces the memory size. Also, to reduce the cost, we realize the parallel by using both on-chip and off-chip memories. We show a design algorithm for the parallel to store given off-chip and on-chip memories. The parallel has a simple architecture and performs lookup by using complete pipelines those insert the pipeline registers in all the paths. We loaded more than 340 K IPv6 pseudo prefixes on the Xilinx Virtex 6 FPGA with off-chip DDRII+ Static RAMs (SRAMs). Its lookup speed is 1.100 giga lookups per second (GLPS) which is sufficient for the required speed for a next generation 400 Gbps link throughput. As for the normalized area and lookup speed, our implementation outperforms existing FPGA implementations.

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 Iguratimod (), a disease-modifying antirheumatic drug launched in September 2012, has been reported to carry a risk of severe hemorrhages through a suspected interaction with warfarin (WF) in the all-case surveillance and early postmarketing-phase vigilance. To elucidate possible mechanisms of adverse interaction between and WF, we analyzed the effects of on the pharmacodynamics and pharmacokinetics of WF in rats. was orally administered to male Wistar rats once daily for 5 d at 10 or 30 mg/kg in combination with WF at an oral dose of 0.25 mg/kg. Coadministration of 30 mg/kg enhanced the anticoagulant activity of WF; prolonged blood coagulation time (prothrombin time and activated partial thromboplastin time) and decreased levels of vitamin K (VK)-dependent blood coagulation factors (II, VII, IX, and X) were observed. On the other hand, the pharmacokinetic parameters of WF including maximum plasma concentration (C_max) and area under the plasma concentration-time curve from 0 to 24 h (AUC_{0-24 h}) were not affected by the combination with . alone did not change blood coagulation time at doses up to 100 mg/kg, while VK-dependent blood coagulation factors decreased slightly at 30 and 100 mg/kg. These results suggest that the pharmacodynamic effect of on VK-dependent blood coagulation factors is involved in the mechanism of drug-drug interaction of with WF.

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No research reports for the application of HClO₄ in the field of internal electro-analysis have been given in the literature despite the valuable properties of this acid.
HClO₄-acid is non-oxidizing at ordinary diluted solution and suffers no reduction by electrolysis. Furthermore, most of its salts, as a rule, are readily soluble, and for this reason of solubility being so high, it may be an excellent acid to use in electrolysis where liquid-Pb-Hg anode is required.
It may be very plausible that these properties pointed above could be applicable to the internal electrolysis with favourable results. Bearing these facts in mind, the writer has conducted the present investigation.
According to the writer’s experiments,copper deposition is not effected except in the presence of Mn,Mg,Cd,Ni,Co,Zn,Pb,Al,Cr,Sn(IV) and As(V). As for Fe or V,somewhat higher results are given from the solution of low acidity. On the other hand, in the case of the presence of large quantity of Sb, heigher results are obtained, owing to the partial deposition of Sb.
Summarizing the experimental results noted above, the analytical procedure using liquid-Pb-Hg anode are given for the determination of Cu in alloys such as bronzes, brasses containing Sn and monel metal, and the results indicate that the procedure is excellent.

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This report aims to inform the current state of geography education in Japan to countries abroad. An organized effort to create such a report is the first since 1980 when the

convention was held in Tokyo. This report aims to present the trends in Japan’s geography education since 1980, although trends before 1980 may be discussed depending on the topic. Chapter I provides an overview about the general geography curriculum in Japan. The Ministry of Education, Culture, Science, Sports and Technology (MEXT) created the Course of Study to serve as a standard for the educational curriculum. Therefore the historic development of the Course of Study is classified. Chapter II presents a discussion of articles and research results concerning geography education during this time period. The subsections are overall review, geography education research, foreign research, geography curriculum/coursework composition theory research, cognitive research, and geography education content theory/methodology theory research. Chapter III describes the promotional activities and training activities promoted by academic groups. The main focus of this chapter will describe the activities that are targeted for school teachers and children/students regarding geography education.

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三重大学は，環境資格支援教育プログラムの充実化や国際環境教育プログラムの確立，実施をお こなうことで，優れた環境人材を育成することを目指している。具体的には，プログラム修了時に 取得することができる学内環境資格は地域だけでなく世界に通用する三重大ブランドの環境資格と して育て上げ，質の高い環境教育プログラムの構築と環境PDCAシステムを確立することである。 この｢三重大ブランドの環境人材養成プログラム｣は，平成20年度に文部科学省の｢質の高い大 学教育推進プログラム｣（教育GP）として選定され，平成22年度までその取り組みが実施されて いる。 この取り組みにおいては，国際的に通用する国際環境人材を養成するために，アジア・太平洋地 域の大学（モンゴル・ロシア・中国・韓国・日本・タイ・インドネシア・オーストラリア・アメリ カ，9カ国33大学）により環境教育コンソーシアムを構築し，国際環境教育の強化を図っている。 また，その成果を客観的に評価・実証することで，持続可能な社会構築に寄与できる大学の社会的 責任（USR）を果たすことが期待される。さらに，教育目標として，三重大学の「三重から世界 へ：地域に根ざし，世界に誇れる独自性豊かな教育・研究成果を生み出す」というに概念の下，次 の三つを掲げている。 1 ．｢感じる力｣・｢考える力｣・｢生きる力｣・｢コミュニケーション力｣がみなぎる。 ．地域に根ざし国際的にも活躍できる。 3 ．実践力を身につけた環境マインドの高い学生の輩出につなげる。 さらに，産官学民連携の環境資格支援教育プログラムの授業を通して得られた環境資格は，三重 大ブランドの環境資格として卒業後も地域に通用，貢献できるものである。

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【目的】関節リウマチ（RA）加療におけるイグラチモド（

）の有効性と安全性について検討した．【対象と方法】当院通院加療中のRA患者のうち，使用中・使用歴のある61例を対象とし，の処方状況，併用薬，継続状況と副作用，投与開始前から52週までの疼痛関節数，圧痛関節数，患者・医師VAS，疾患活動性について調査した．【結果】の処方状況は追加併用38例，切り替え4例，第一選択薬として1例で処方され，全例csDMARDsが併用され，プレドニゾロン49％，生物学的製剤16％の併用を認めた．服薬継続例42例，副作用中止17例，効果不十分中止例であった．圧痛関節数，腫脹関節数は投与開始後8週で，患者VASは8週，医師VASは12週で有意に低下，疾患活動性指標であるDAS28-CRP，SDAI，CDAIも8週で有意に低下していた．有効群は投与開始前の疾患活動性の低い症例であった．

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[Objectives] The combined effects of a new antirheumatic drug, iguratimod () with anti-tumor necrosis factor (TNF)α antibody (aTNFAb) were examined in two mouse models of arthritis.
[Methods] In collagen-induced arthritis (CIA) model, arthritis was induced by immunization with type II collagen on day 0 and 21. was orally administrated once daily and aTNFAb was intraperitoneally injected twice a week from day 25 to day 34. In glucose-6-phosphate isomerase (GPI)-induced arthritis model, arthritis was induced by immunization with recombinant GPI on day 0 and the treatments were started on day 5. was orally administrated daily and aTNFAb was intravenously injected every other day to day 14. Efficacy was evaluated using arthritis scores, articular destruction scores, and blood biochemical analyses.
[Results] In the CIA model, the combination of and aTNFAb significantly inhibited the arthritis and articular destruction more effectively than as monotherapies. Serum interleukin (IL)-1β and IL-6 levels were also reduced significantly with combined treatment. The decline in serum levels of cartilage oligomeric matrix protein (COMP) and matrix metalloproteinase (MMP)-3 was significantly enhanced with the /aTNFAb combination. In the GPI-induced arthritis model, and aTNFAb lowered the arthritis scores and the combination of both treatments showed a significant effect compared with alone. Regarding anti-GPI titers on day 14, and/or aTNFAb showed no significant effect.
[Conclusion] In the two mouse models, the combination of and aTNFAb showed greater benefit than either monotherapy, suggesting such combination therapy would be effective in clinical use.

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【目的】イグラチモド（

）は2012年に薬価収載された新規抗リウマチ薬である．の腎機能に与える影響を検討する．【対象・方法】新潟県立リウマチセンターで2015年から2016年の間にを処方開始した201例（男性58例，女性143例，年齢68（60-77）歳）で開始前，開始後3カ月，6カ月の臨床データを2017年12月に診療録から後方視的に調査した．が中止された症例では中止時と中止後3ヶ月のデータを調査した．【結果】開始後3ヶ月で関節リウマチの疾患活動性は有意に低下した（DAS28-ESR 4.1（3.-4.8）v.s. 3.（.3-4.1）, p<0.001）．estimated glomerular filtration rate（eGFR）は開始前と比較して3ヶ月後で有意に低下した（eGFR 77.3（63.9-91.）, 68.3（54.8-81.4）, p<0.001）．6ヶ月以内に51例がを中止していたが，7例は腎機能低下が中止原因だった．中止例では中止時に比較して中止後3ヶ月でeGFR値は有意に上昇した（eGFR 70.7（57.6-79.7）v.s. 75.7（63.4-88.7）, p=0.002）．多変量解析ではeGFR10ml/min以上低下に関わるリスク因子として非ステロイド性抗炎症薬（NSAIDs）の併用ありが抽出された．【結論】重篤な腎機能障害は少なかったが，開始後，有意にeGFR値は低下した．使用時には肝障害だけでなく腎障害にも留意する必要がある．しかし中止後は回復がみられており，可逆性の変化であることが示唆された．

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This paper presents a method to realize index generation functions using multiple Index Generation Units (IGUs). The architecture implements index generation functions more efficiently than a single

when the number of registered vectors is very large. This paper proves that independent linear transformations are necessary in IGUs for efficient realization. Experimental results confirm this statement. Finally, it shows a fast update method to IGUs.

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