Background

The differences in conditions of enteric-coated acid-labile drug release and absorption between healthy subjects in bioequivalence studies and gastrointestinal patients in clinical practice can lead to significant differences in gastric stability of original PPIs and generics. Thus, pathologic duodenogastric reflux (PDGR) and the pH increasing within PPIs administration still remain unaccounted for.

Methods

Two-stage modified comparative dissolution testing of original omeprazole (OO) and four generics (G1;2;

;4) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±.05) to pH . (.±.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH exposure time of resistance to PDGR for omeprazole is 4 minutes, i.. the active substance should not be released within 4 minutes at pH . The exposure at the second stage was conducted with pH 4 (4.±.05), that imitated gastric pH after PPI administration. And then we also moved drugs to pH with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after 4, 10, 15, 20, 30, 45, 60 minutes in pH

solution at the first stage were different for OO and generics. For OO, these values were 4,±,%; 41,4±,%; 62,8±4,%; 79,±2,%; ,±2,%; ,±2,%; ,±4,4%; for Generic1 - ; 49,±,%; ,8 ±2,8%; ,4±,%; , 2±2,2%; 87,±2,%; 85,±1,1%; for Generic2 - ; 30,±,%; 66,±8,2%; 76,4±,4%; ,8±,%; 86,±,%; ,±,%: for Generic - ,8±,%; ,±1,%; , 8±,2%; ,±2,%; ,±2,1%; ,1±2,%; ,±2,4%; for Generic4 - ,±1,%; ,4±,8%; ,2±1,2%; , ±,%; ,±,%; ,±,%; ,8±1,1%, respectively.

An analysis of the omeprazole concentration in pH

solution at the second stage revealed the following parameters after the same time: for OO - 4,4±,%; 40, ±,%; 62,8±2,%; ,±,1%; 85,4±2,%; ,8±,4%; ,±,%; for Generic1 - ; 67,±,8%; 89,±2,%; 91, ±4,%; 89,1±1,%; ,±1,4%; 87,8±1,2%; for Generic2 - ; 42,2±,%; 75,1±,%; ,±,%; ,4±,2%; , ±1,%; 87,±1,%; for Generic4 - 85,±,%; 85,±,%; ,±,%; ,±,%; ,4±,%; ,4±,%; ,±,4%, respectively. Generic release and degradation were completely realized at pH 4.

Conclusion

Decreased gastric stability of Generic

and Generic4 makes PDGR and inhibited gastric acid secretion due to PPIs administration the potential causes of decreased enteric-coated acid-labile drugs stability.

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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 () 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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The possibility of attenuation of microseismic waves due to the presence of an upward folding of the ocean bottom into the liquid is discussed in this paper. The upward folding of the ocean bottom has been idealized by means of an irregularity in the form of a rectangle intruding into the liquid and the evaluation of the displacement component at any point of the solid medium has been carried out in two stages. First, the change in the incident mode of the surface wave due to the presence of the rectangular irregularity has been determined, and second, the subsequent change of the resulting displacement components due to the termination of the liquid layer and the step change in elevation of the solid medium at the continental margin has been discovered. Finally, numerical calculation has been made to determine the attenuation of the microseismic waves of different periods due to the presence of the rectangular irregularity at the ocean bottom.

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This paper outlines a mathematical description of the stress dilatancy behaviour of granular materials which accounts for stress level and void ratio dependencies. The consideration of these aspects has important implications in the modelling of granular material behaviour. In fact, granular material mechanical response is largely dominated by the evolution of dilatancy, fabric and void ratio histories. The starting point in this study is the well established Rowe's theory which is revisited and ultimately modified by introducing a factor linked to governing state parameters in order to describe the complete behaviour of granular materials during deformation. Numerical simulations of triaxial tests on granular materials at different void ratios and stress levels are herein presented to illustrate the model.

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(,)-2,-エポキシ-,,11,11-テトラメチルシクロウンデカ-,-ジエン(2)をフムレン1((2,,)-,,11,11-テトラメチルシクロウンデカ-2,,-トリエン)より合成する既知の合成法は実際に牧率が低く合成的に問題がある.さらに,2の合成はその反応性や物性の研究のために簡単に高牧率で行われることが望まれる.今回,2の新たな合成法と簡便な精製法を見いだし,2を高牧率で1から合成することができたので報告する.1のジエポキシ化,続く再結晶により得られたジエポキシド(8)は二価のチタンにより還元されて,1(273%)と8(25%)と少量のを含む2を主生成物(42.%)として与えた.1とは原料として再利用できる.2の精製は1と同様硝酸銀()錯体の結晶で行い,純粋な2は1から通算牧率32.%で得られた.2の既知方法による合成は4段階の反応と数回のカラム分離及び10%含浸シリカゲルカラム分離を必要とし牧率が極端に低い.今回,新しい2の合成法は2段階の反応で1回のカラム分離と再結晶により高い通算牧率を示す.

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A method for analyzing the uncertainties involving the use of empirical relationships in design is developed. It is applied to evaluate the reliability of the relationship s_u(mobilized)=(measured), whereby the pertinent uncertainties are analyzed using extensive laboratory and field observed data. On the average, the relationship s_u(mobilized)= (measured) is unbiased and the error implicit in the relationship is about 15%. When cone values are used to infer s'_p, additional uncertainties on the mobilized undrained strength will incur resulting mainly from the calibration uncertainty between σ'_p and the cone values. Alternatively, vane tests may be performed to infer the mobilized strength using Bjerrum correction factor. Results show that uncertainty level associated with using the vane tests is smaller than that using the cone values, provided that similar scatter is observed between measured vane and cone values at a given site. However, prediction of the mobilized strength is even more accurate if direct measurements can be made on the preconsolidation pressure. The proposed probabilistic method also assesses the benefit of additional tests besides comparing the accuracy of using various soil parameters for predicting mobilized undrained strength. Such information is essential for planning cost-effective site characterization program.

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L'entree en Iran des armees britannique et sovietique s'est produite en aout 1941. Elle ebranla du coup le regime de la dynastie pahlavi qui etait au pouvoir depuis 16 ans, et mena le pays vers l'instabilite politique et le chaos social. La defaite de l'arme gouvernementale, qui etait le pivot du regime de Reza Shah, reduisit considerablement le controle du gouvernement central dans le pays. Cette situation politico-sociale confuse permit le developpement de differents mouvements politiques en Iran. C'est ainsi que le 16 aout 1942 le parti clandestin Komeley Jiyanewey Kurdistan (J-K) est ne a Mehabad, une ville au nord-ouest de l' Iran. Des sa formation, ce parti a su etendre sa sphere et, en une courte periode de temps, a fini par mettre sous son influence la ville et ses alentours. A la fin de la Seconde Guerre mondiale, en ete 1945, le J-K etait devenu une organisation representant le mouvement nationaliste kurde en Iran. C'est a ce moment-la qu'un autre parti politique, le Hizbi Dimokratiki Kurdistan (HDK), fonde par Qazi Mihemed a Mehabad aussi, devait remplacer le J-K. Des le janvier 1946, le HDK proclama l'instauration de la≪Republique de Kurdistan≫. Cependant, les troupes sovietiques qui avaient pris sous leur protection la Republique evacuerent les terres iraniennes, en mai 1946. Six mois plus tard, sous la pression militaire du gouvernement central iranien, la republique s'ecroula. Deux theories tentent le passage du J-K au HDK. William Eagleton Jr., par exemple, affirme dans The Kurdish Republic of 1946 que le HDK a ete cree sur le conseil des autorites sovietiques. L'ex-secretaire general du Parti Democratique du Kurdistan , 'Ebd el-Rehman Qasimlu maintient par contre que Qazi Mihemed a etabli le nouveau parti de sa propre initiative, eu regard a la situation politique de cette epoque-la. Il considere que la passage du J-K au HDK comme etant l'evolution parti nationaliste clandestin en un parti democratique. En analysant ces deux theories et en se basant sur les autobiographies des personages qui se sont engages dans cet evenement, cette etude tentera le principe directeur et les activites du J-K et de mieux comprendre les raisons pour lesquelles le J-K devait etre remplace par le HDK. La conclusion generale portera sur les differents objectifs politiques du J-K et du HDK. Le J-K visait l'elevation du niveau culturel du peuple tout en luttant contre le tribalisme, qui etait, selon lui, le probleme majeur de≪la nation kurde≫, et cela en ecartant toute idee de revolte militaire. Le J-K a aussi exclu de son cadre les elites sociales telles que les leaders des tribus et dirigeants religieux de peur qu'ils n'excercent une influence sur les membres du parti. L'automne de 1944 fut le debut nouvelle ere pour le mouvement kurde. Alors que l'espoir de l'autodetermination augmentait parmi le peuple a mesure que s'approchait la fin de la guerre, la necessite de la force militaire a commence a se faire sentir dans le J-K. C'est pour cela que s'est produite au sein du parti une tendance a compter sur l'aide militaire des sovietiques et a recourir au leadership de Qazi Mihemed, qui avait une certaine influence meme sur les leaders tribaux. Mais cette tendance etait essentiellement incompatible avec la ligne fondamentale du J-K et, graduellement, a prive ce parti de sa raison . Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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BCR-ABL1 International Scale（IS）測定はチロシンキナーゼ阻害剤で治療されている慢性骨髄性白血病（CML）患者の治療効果をモニターする上で重要な検査法である。稀ではあるが，BCR-ABL1 IS測定ができないCMLが存在することが知られている。本研究において，我々は，そのようなBCR-ABL1 IS測定のできないCML患者を経験し，分子生物学的な方法で，その原因を解明した。本例ではABL1遺伝子における切断点がa2エクソン内にあることが分かり，そのことがABL1のa2エクソンを欠いた

14a（a）キメラ遺伝子のmRNAのみの発現を誘導していた。a2エクソンは本邦における検査部でのIS測定において重要な要素であり，これが欠損することが測定不能の原因であった。このようなIS測定ができない稀なCML症例をさらに集積して，その分子構造を解明することが待たれる。

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We screened the differentiation-inducing activities of 39 mushroom extracts from Akita prefecture, Japan, on the mouse osteoblastic cell line, MCT-1. Sixteen phosphate buffered saline (PBS), 8 boiled PBS, 14 ethanol and 12 methanol extracts induced alkaline phosphatase (ALP) activities, an indicator of MCT-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-,,-triol (1). 1 induced ALP activities of MCT-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 MCT-1 cells by 1, ergosterol (2), ergocalciferol (), cholesta-,,-triol (4), -dehydrocholesterol () and cholecalciferol () were tested. The enzyme activities of MCT-1 cells were increased .-fold by 10 μM 1 and 2.4-fold by 10 μM 4. However, 2, , and did not induce MCT-1 cell ALP activity at .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 MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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A boron treated copper bearing HSLA steel containing austenite formers like manganese and nickel, somewhat lower in amount than that in HSLA 100 variety of steel is chosen for the study. The role of thermomechanical processing on the microstructure and mechanical properties of the above steel has been investigated. Differential scanning calorimetric study is carried out for understanding the precipitation behaviour of copper in HSLA steel under the influence of boron. The microstructure of the experimental steel is found to consist of laths of martensites and bainite. MA constituents of ribbon like morphology are observed at the lath boundaries. Higher strength properties of the steel are attributed to the presence of finely distributed precipitates of copper and microalloy carbides.

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The pseudo-static analysis has been used in engineering practice to simplify the computation of the upper limit of a slope under seismic load. In this paper, the upper bound technique of limit analysis of perfect plasticity is used to determine the bearing capacity of a foundation near a down-hill slope. In this analysis (Chen et al., 1969; Chen, 1975), a logarithmic spiral rapture (Abdul-Baki et al., 1970; Sawada et al., 1984) is assumed to start at an edge of the loaded area far from the slope. A landslide is assumed to be of rigid body type with the inertia force acted at its center of gravity. The collapse state is reached when the rate of kinematic energy of the landslide together with the load is equal to the rate of dissipation of internal energy along the sliding surface. This energy balance leads to the equation of ultimate load with several parameters. The optimized numerical rcsults with respect to these parameters are compared with those by Kotter's method (Yamaguchi, 1959) and those obtained by the slice method.

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Nアルキル,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,,-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,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-,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-,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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