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The forearc in Northeast Japan subsided (3–4 mm/year) in the interseismic ~100 years before the 2011 Tohoku earthquake (MW9.1) just like it did during this event. This study attempts to understand the mechanism of the vertical displacement of the forearc during gigantic earthquake cycles via numerical modeling. The results suggest that the interseismic subsidence rate in the forearc increases with the duration of the locking of the asperity of the gigantic earthquake over several hundred years, due to the increasing slip deficit rate on the deeper parts of the plate interface. The increasing slip deficit rate is caused by both the decreasing the shear stress in the shear zone owing to the continuous locking of the asperity and the increasing the mobility of the continental lithosphere owing to the viscoelastic relaxation in the mantle wedge. The deep slip deficit rate extending to ~100 km depth of the plate interface is necessary to explain the observed interseismic forearc subsidence rate. The results also suggest hundreds of years of continuous locking of the asperities of a gigantic earthquake in the western Kuril subduction zone, where fast forearc subsidence has been observed as well., 東北地方太平洋沿岸域が沈降するメカニズムを解明 --超巨大地震サイクル後半の沈降速度の増加--. 京都大学プレスリリース. 2019-04-09.

Using two-dimensional finite element modeling, we reproduced the observed postseismic deformation of the 2011 Tohoku-Oki earthquake. Our model, which accounts for the lithosphere-asthenosphere boundary and weak zones beneath volcanoes, was able to reproduce small-scale (

To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl ω-chain moiety of the γ-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented.

A series of γ-lactam prostaglandin E(1) analogs bearing a 16-phenyl moiety in the ω-chain and aryl moiety in the α-chain were synthesized and biologically evaluated. Among the tested compounds, γ-lactam PGE analog 3 designed as a structural hybrid of 1 and 2 was discovered as the most optimized EP2/EP4 dual agonist with excellent subtype-selectivity (K(i) values: mEP2=9.3 nM, mEP4=0.41 nM). A structure-activity relationship study is presented.

To identify topically effective EP4 agonists and EP2/EP4 dual agonists with excellent subtype selectivity, further optimization of the 16-phenyl ω-chain moiety of the γ-lactam 5-thia prostaglandin E analog and the 2-mercaptothiazole-4-carboxylic acid analog were undertaken. Rat in vivo evaluation of these newly identified compounds as their poly (lactide-co-glycolide) microsphere formulation, from which sustained release of the test compound is possible, led us to discover compounds that showed efficacy in a rat bone fracture healing model after its topical administration without serious influence on blood pressure and heart rate. A structure-activity relationship study is also presented.

To identify potent EP2/EP4 dual agonists with excellent subtype selectivity, a series of γ-lactam prostaglandin E analogs bearing a 16-phenyl ω-chain were synthesized and evaluated. Structural hybridization of 1 and 2, followed by more detailed chemical modification of the benzoic acid moiety, led us to the discovery of a 2-mercaptothiazole-4-carboxylic acid analog 3 as the optimal compound in the series. An isomer of this compound, the 2-mercaptothiazole-5-carboxylic acid analog 13, showed 34-fold and 13-fold less potent EP2 and EP4 receptor affinities, respectively. Structure activity relationship data from an in vitro mouse receptor binding assay are presented. Continued evaluation in an in vivo rat model of another 2-mercaptothiazole-4-carboxylic acid analog 17, optimized for sustained compound release from PLGA microspheres, demonstrated its effectiveness in a rat bone fracture-healing model following topical administration.

Novel dehydrative glycosylation with 1-hydroxy sugars as glycosyl donors was achieved. Combination of trifluoroacetic anhydride or trichloroacetic anhydride as dehydrating agents with TMSClO4 as a Lewis acid afforded desired glycosides in good yields. t-Butyldiphenylsilyl and trichloroethoxycarbonyl groups at the 6-position of donors enhance α-selectivity of the glycosylation.

A series of novel N -acylsulfonamide analogs were synthesized and evaluated for their binding affinity and antagonist activity for the EP3 receptor subtype. Representative compounds were also evaluated for their inhibitory effect on PGE 2 -induced uterine contraction in pregnant rats. Among those tested, a series of N -acylbenzenesulfonamide analogs were found to be more potent than the corresponding carboxylic acid analogs in both the in vitro and in vivo evaluations. The structure activity relationships (SAR) are also discussed.

The process of discovering a series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acid analogs is presented since these compounds represent a new class of potent, selective, and orally active prostaglandin D2 (PGD2) receptor antagonists. Most of these compounds exhibit strong PGD2 receptor binding and PGD2 receptor antagonism in cAMP formation assays. When given orally, these new antagonists dramatically suppress allergic inflammatory responses, such as the PGD2-induced or OVA-induced increase of vascular permeability. Structure-activity relationship (SAR) data are also discussed.

A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and evaluated for prostaglandin D(2) (DP) receptor affinity and antagonist activity. Some of them exhibited strong receptor binding and were potent in the cAMP formation assays. These antagonists also suppressed allergic inflammatory responses such as the PGD(2)-induced increase of microvascular permeability. Structure-activity relationship (SAR) data are presented.

A series of N-(p-alkoxy)benzoyl-5-methoxy-2-methylindole-3-acetic acids and N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid were discovered as new chemical leads for a prostaglandin D2 (PGD2) receptor antagonist. Most of them exhibited PGD2 receptor binding and blocked cyclic adenosine 3′,5′-monophosphate (cAMP) formation in vitro. In particular, 2-methylindole-4-acetic acid analog 1 showed markedly increased receptor affinity and cAMP antagonist activity. Chemistry and structure activity relationship (SAR) data are also presented.

The process of discovery for highly potent prostaglandin D(2) (PGD(2)) receptor antagonists is reported. A series of N-(p-alkoxy)benzoyl-2-methylindole-4-acetic acids were synthesized and identified as a new class of selective PGD(2) receptor antagonists. Most of them exhibited strong PGD(2) receptor antagonism in binding studies and the cAMP formation assay. The structure-activity relationships (SAR), including subtype selectivity of the synthesized compounds, are also discussed.

A series of Indomethacin analogs were synthesized and biologically evaluated. Among the compounds tested, N-(p-butoxy)benzoyl-2-methylindole-4-acetic acid 2 was discovered as a new chemical lead for a prostaglandin D2 (PGD2) receptor antagonist. Structure–activity relationship data are also presented.

Novel dehydrative glycosylation with 1-hydroxy sugars as glycosyl donors was achieved. Combination of trifluoroacetic anhydride or trichloroacetic anhydride as dehydrating agents with TMSClO4 as a Lewis acid afforded desired glycosides in good yields. t-Butyldiphenylsilyl and trichloroethoxycarbonyl groups at the 6-position of donors enhance α-selectivity of the glycosylation.

Versatile use of the p-nitrophenyl group for anomeric protection of carbohydrates is described. It can be readily removed via conversion into a p-acetamidophenyl group followed by ammonium cerium(IV) nitrate oxidation.

In order to improve the cutting ability of fine-grain abrasive stone, the relation between the cutting mechanism in the superfinish and the working condition of superfinish has been investigated. Thus, the following results are obtained. As to the cutting motion in the superfinish, it is found that the frequency of stone oscillation has an upmost influence to the cutting mechanism among the various conditions of cutting motion, secondly the surface speed of work and amplitude of stone oscillation influence in same order to the cutting mechanism. When the superfinishing fluid (mixture of kerosene and oil) of higher viscosity is prefered, it is necessary to increase the cutting direction angle in order to get the most efficient condition of cutting performance. In addition, the characteristics of honing process may be classified into "cutting", "semicutting" and "mirror-finishing" according to the values of stone pressure and cutting direction angle.