背景と目的：ステロイド性骨粗鬆症は，積極的な治療介入が必要とされる．その第一選択薬はビスホスホネート製剤（以下ビス）であるが，近年，デノスマブ（以下デノス）も注目を浴びている．ステロイド性骨粗鬆症の骨密度に対する両者の効果を比較検討した．

方法：ステロイド性骨粗鬆症の管理と治療ガイドライン：2014年改訂版の薬物療法開始の基準を満たした患者を対象とした．無治療群（N群）と，治療介入群として当初よりビスで治療したBB群，ビス後デノスに変更したBD群，デノスで治療したDD群，デノス後ビスに変更したDB群を抽出し，ステロイド投与を開始した時，ステロイド性骨粗鬆症に対する治療を開始した時または薬剤変更から

カ月後の腰椎，大腿骨頚部と大転子部の骨密度を測定し，それらの変化を統計学的に比較検討した．

結果：149例が抽出され，その内訳は，N群48例，BB群24例，BD群

例，DD群21例，DB群34例であった．治療開始時または薬剤変更からカ月後にBD群を除くすべての治療介入群で腰椎の骨密度が上昇した．大腿骨の骨密度は，BD群において薬剤変更後に上昇に転じた．

考察：デノスにはビスと同様の骨密度上昇効果があると考えられた．

結論：デノスは，ステロイド性骨粗鬆症治療の第一選択薬となり得る．

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The ability of Climacodon septentrionalis to immobilize and kill a mycophagous nematode (Aphelenchoides sp.) in vitro is described for the first time. Two isolates produced droplets (20–45 μm in diameter) that formed at the apices of tall, stalked, and branching secretory cells (700–1,500 μm tall). On 2% modified malt extract agar, nematodes became enveloped in the droplets, which restricted their ability to move and resulted in complete immobilization and death within several hours of contact. The rate of decomposition of the nematodes varied considerably, with most individuals persisting for weeks whereas others were degraded within several days and appeared to be colonized by dense hyphal growth. This study provides the first documentation of a non-agaricoid fungus producing secretory cells that are able to immobilize nematodes.

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MC3T3-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MC3T3-1 cell differentiation. The enzyme activities were markedly induced by extracts of Tricholoma auratum, and we isolated the active compound from methanol extracts of this mushroom. Physical data for the isolated active compound were identical to those for (,24R)-ergosta-,-diene-3β,,-triol (1). 1 induced ALP activities of MC3T3-1 cells and promoted cell proliferation. To investigate the relationships between the chemical structure and differentiation-inducing activity of the compound, ALP-inducing activities of MC3T3-1 cells by 1, ergosterol (2), ergocalciferol (3), cholesta-3β,,-triol (4), -dehydrocholesterol () and cholecalciferol () were tested. The enzyme activities of MC3T3-1 cells were increased 3.0-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, 3, and did not induce MC3T3-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C- and/or C- of 1 and 4 played an important role in their differentiation-inducing activities on MC3T3-1 cells. Furthermore, 1 suppressed induction of MC3T3-1 cell apoptosis by serum starvation.

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Some existing analytical methods which have been used in geotechnical engineering are modified to handle the shear strength reduction with time due to softening in fissured, over-consolidated clays and mudstones. These are limit equilibrium analysis of slope stability, calculation of earth pressure and calculation of stress and displacement around a tunnel. The softening effect is incorporated in these analyses using the failure criterion and the time-dependent strength parameters proposed previously by the authors. Examples are presented which emphasize the importance of appreciating the softening effect in analyses and further illustrate that the effect of shear strength reduction with time due to softening could easily be captured with existing analytical methods.

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The design implication of stress-confinement effect of nonwoven geotextile is addressed. The unconfined and confined strengths of a selected needle-punched nonwoven geotextile are used to conduct a comparative design of a granular soil retaining wall based on a limit equilibrium approach. A higher wall may be allowed when considering the confined strength as compared to the unconfined strength. For a selected wall height, confined strength allows for fewer geotextile layers when compared to that designed using unconfined strength. It is recommended that stress-confinement test procedure should be standardized so that confinement effect of some nonwoven geotextiles may be incorporated into an individual wall design procedure.

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百歳以上高齢者32名を非痴呆群と痴呆群に分類し, 等電点イムノブロッティング法によりアポ 表現型を測定した。非痴呆群は21名 (65.%), 痴呆群は11名 (34.4%) で全例アルツハイマー病 () であり, 後者の平均発症年齢は97.歳と超高齢であった。アポ表現型は, 痴呆群で3/3 (α%), 3/4 (I1%) のみ出現し, 非痴呆群と比較して有意差が認められず, 百歳以上高齢者においてアポ表現型と発症との間に関連を認めなかった。アポ遺伝子の解析は, ε2, ε4出現の痴呆発症における関与は否定的であり, アポε2が痴呆群で検出されなかった。

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It has been shown after mathematical and mechanical investigation that Limit Equilibrium Method (LEM) can be considered as a method to obtain the necessary condition of Slip Line Method (SLM), and that the solution can be obtained under the condition that F_s=1 and ∂F_s/∂θ=O, where F_s is the safety factor and θ is the inclination of the plane on which the safety factor is defined. Next, the generalized LEM (GLEM) is proposed, dealing with the following points : (1) Triangular or quadrangular blocks can be treated; (2) Safety factors are defined also on interblock planes; and (3) All types of plastic problems, slope stability, bearing capacity, and earth pressure are identically formulated. Two situations regarding treatment of the moment equilibrium condition are discussed. GLEM is applied to well-known problems. The results agree well with those obtained by theoretical methods. GLEM can be used to obtain the distribution of earth pressure or bearing capacity. GLEM, Iike ordinary LEM, is very effective for the practical problems, but GLEM is more theoretical and it can result in more accurate solutions.

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Nアルキル3,4:,10-ペリレンテトラカルボン酸モノアンヒドリド=モノイミド[4a～]と芳香族アミン(アニリン,p-トルイジン,p-アニシジン,3,-キシリジン,4-アミノナゾベンゼン,およびo-フェニレンジアミン)を縮合して非対称型3,4:,10-ペリレンビス(ジカルボキシミド)誘導体-N-アルキル-N'-アリール-3,4:,10-ペリレンビス(ジカルボキシミド)(〔a～〕,〔a～〕,〔a～〕,〔8a～〕,〔a～〕,および〔10a～〕)を合成した. これらの各誘導体はすべて赤色系の色相を示し, 顔料試験の結果N-ブチル-N'-アリール-3,4:,10-ペリレンビス(ジカルボキシミド)(たとえば〔〕や〔〕)がとくにすぐれた耐光性を示した.

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Amyloid β (Aβ) plays a key role in the pathology of Alzheimer’s disease (

) and is toxic owing to its ability to aggregate into oligomers and fibrils. Aβ has high aggregative ability and potent toxicity due to the “toxic turn” at positions and 23. Furthermore, APP knock-in mice producing P-Aβ with the toxic turn exhibited -related phenotypes such as cognitive impairment, Aβ plaque accumulation, and tau hyperphosphorylation. In these mice, it is suggested that the activation of neuroinflammation and dysregulation of hypoxia-inducible factor (HIF) expression in the hippocampus contribute to the pathogenesis of -related phenotype. However, it remains unclear which cells are responsible for the dysregulation of HIF expression and the neuroinflammation which was induced by P-Aβ with the toxic turn. Here, we investigated the effects of chronic treatment with P-Aβ42 and lipopolysaccharides (LPS) on the inflammatory response in BV-2 microglia. Chronic treatment with P-Aβ42 and LPS increased nitric oxide production and the expression of interleukin- (IL-), whereas it reduced the expression of HIF-1α and HIF-3α in BV-2 microglia. The reduction of HIF-1α caused by P-Aβ42 and LPS was milder than that caused by LPS. Furthermore, chronic treatment with P-Aβ42 and LPS increased the nuclear translocation of nuclear factor-kappaB (NF-κB). P-Aβ42 could enhance the inflammatory response of microglia with abnormal HIF signaling and contribute to the progression of pathology.

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Using the so-called pseudo-static method, a stability analysis was made for the mountain slide that took place at Mitake-iriya village at the time of the Izu-Ohshima-Kinkai earthquake of January 14, 1978. Undisturbed samples of volcanic clay were obtained in blocks from the exposed surface of the deposit identified to have been the sliding surface. The partially saturated clay samples were tested under consolidated undrained conditions using the triaxial test equipment. Dynamic axial stresses with irregular time histories were applied to the specimens in combination with statically sustained axial stresses to determine the soil strength under the conditions simulating in-situ states of stress during the earthquake. The results of the tests were expressed in terms of the Mohr-Coulomb type failure criterion which showed that, while the angle of internal friction remained almost unchanged, the cohesion component in irregular loading increased above values obtained in the static loading. Using the strength parameters thus determined, a pseudo-static analysis was made to check the stability of the soil masses that had actually slid during the 1978 earthquake. The maximum horizontal acceleration required to cause the slide was computed. The computed accelerations were shown to cover a range between 400 and 500 gals which is consistent with the range estimated by other investigators on the basis of overturning of tombstones in the vicinity of the slide area.

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