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±0.05) to pH .0 (.0±0.05) 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 (4.0±0.05), 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,±0,%; 41,4±,0%; 62,±4,0%; 79,±2,9%; ,±2,9%; 81,±2,9%; 80,±4,4%; for Generic1 - 0; 49,±9,9%; , ±2,%; 90,4±,%; , 2±2,2%; 87,±2,0%; 85,9±1,1%; for Generic2 - 0; 30,±,%; 66,±,2%; 76,4±,4%; ,±,%; 86,0±,%; 84,±,%: for Generic - 80,±,%; ,±1,9%; , ±,2%; ,±2,%; 81,9±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,±1,%; 84,4±0,%; 84,2±1,2%; , 9±0,9%; ,9±0,9%; ,9±0,9%; ,±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±0,%; 40, ±,0%; 62,±2,0%; 80,0±,1%; 85,4±2,9%; ,±,4%; 80,9±,%; for Generic1 - 0; 67,0±,%; 89,±2,%; 91, 9±4,%; 89,1±1,%; ,±1,4%; 87,±1,2%; for Generic2 - 0; 42,2±,%; 75,1±,%; 81,0±,0%; ,4±,2%; , ±1,%; 87,9±1,0%; for Generic4 - 85,±0,%; 85,±0,%; 84,±0,9%; ,±,0%; 84,4±0,%; 84,4±0,%; 84,±0,4%, 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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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), 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 .0-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 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 MCT-1 cells. Furthermore, 1 suppressed induction of MCT-1 cell apoptosis by serum starvation.

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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 d'activite 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 d'expliquer 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 d'Iran, '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 d'un 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 d'examiner 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 d'une 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 d'etre. Ainsi, le HDK se substitua au J-K en tant que≪parti democratique≫visant a rallier d'abord les elites sociales sous sa banniere, en s'appuyant sur l'autorite personnelle de Qazi Mihemed.

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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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Choke disease fungus Epichloe typhina is associated with resistance to leaf spot disease in timothy plants (Phleum pratense). We have proposed the hypothesis that this resistance is caused by antifungal compounds existing in infected plants. We investigated the fungitoxic constituents of the stromata of . typhina. Seventy-eight compounds were isolated, including twenty novel sesquiterpenoids chokols (1,2,-17,19-21,23-26), five novel oxygenated fatty acids(27-31), gamahonolide A(34) and (37), gamahorin(38) and non-fungitoxic chokorin(71) and an anthrasteroid(80). Their structures were determined by spectroscopic methods. The absolute configuration of chokol (2) was elucidated by its CD spectrum with Eu(fod)_ and a chemical correlation with epicyclonerodiol oxide(). Phytol(81), phytyl acetate() and phytyl palmitate() were identified as an inducer of aerial hyphae formation of Cladosporium herbarum. Pinoresinol(60) and diosmetin(73) were metabolized in cultures of . typhina. Pinoresinol(60) was transformed into C norlignan(59) and α-ribofuranoside(87). Diosmetin(73) was transformed into -O-α-ribofuranoside(). Antifungal activities of the isolated compounds were investigated.

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長期的に見ると、景気のトレンドが低下し、在庫投資や設備投資の変動が小さくなっている。その背景には、経済のサービス化、グローバル化、DX、研究開発投資の拡大などの経済構造の変化がある。こうした中で、第 16 循環の山（2018 年 10 月）付近においては、景気動向指数（一致指数）と実質GDPの動きに乖離が見られたが、その要因としては、外需の減少ペースが景気を一気に冷え込ませるような急激なものではなかったことが大きい。加えて、労働市場では、人口減少下で女性や高齢者を中心に労働市場に参入する人が増え、雇用所得環境を下支えしていた。コロナショック後は、賃上げのモメンタムが強まっている。今後、労働市場の構造変化がどのように進むのか、それが景気循環にどのような影響を与えるのか、注視していく必要がある。 こうした景気循環の特徴の変化やその背景にある経済構造の変化を踏まえると、景気循環を適切に捉えるためには、第一に、景気循環の転換点を敏感に捉える必要があることに変わりはないが、一方で、第二に、生産に過度に重点を置かず、より幅広い指標を観察すること、第三に、経済の全体的な動向を捉えるという観点から、実質GDPの動向にも留意すること、が必要となろう。

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The nucleus ¹²C was bombarded by .1–MeV

3He

particles to study elastic and inelastic scattering and the (

3He

, α) reaction. Angular distributions were measured for the elastic scattering, for the inelastic scattering to levels at 4.4,

7

.

6

and 9.

6

MeV in ¹²C, and for the (

3He

, α) reaction to levels at 0.0, 2.0, 4.

3

(4.

7

) and

6

.4 MeV in ¹¹C. The optical potential parameters were searched for to fit the

3He

elastic scattering angular distribution. The deformation parameters β₂ and

β₃

for ¹²C were determined from DWBA analysis. The angular distributions of α particles were compared with DWBA calculations and calculations including the two-step process via inelastic channel.

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Failure problems of saturated soils are classified in the present study into the following four types : Type I : The failure of loose and/or normally consolidated soils under fully drained loading conditions. Type II : The same soils but under perfectly undrained conditions. Type III : The failure of dense and/or overconsolidated soils under fully drained conditions. Type IV : The same soils but under perfectly undrained conditions. The soil-water coupling limiting equilibrium analysis on the basis of the critical state concept is shown possible to draw a distinction between type I, II and IV problems, and the limitations of the analysis procedure happen in solving the type problem in the above. This is demonstrated experimentally, in which seepage failure experiments in laboratory with the use of a saturated silty sand are employed to make distinctions clearly between the four types of failure problems. The definite distinctions both in failure load and failure mode appeared in the four types of experiments are summarized as follows : (1) the smallest failure load in loose sand in the undrained condition, (2) the largest failure load with the largest failure region in dense sand under undrained loading, () the observation of no global deformation before failure within the soil under the fully drained condition that suggests the development of very localized shear deformation in the sand. Three out of four experiments are described well by the limit analysis computation mentioned above as far as the failure load and the shape and the size of the failure region after boiling failure are concerned, and thus the type III problem is identified to be the problem that should be solved by any other means in near future.

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1. The chromosome numbers of 64 species have been studied on which 56 are investigated for the first time.
2. Morphological, anatomical and cytological findings on the Musaceae in the broad sense are considered from a phylogenetical standpoint and three distinct groups:
a) Musa-Ensete, ) Ravenala-Strelitzia-Phenakospermum and c) Holiconia are recognised as suggested by some authors. For these groups sub-familial status is proposed.
. Lowiaceae have been studied for the first time cytologically and their chromosome morphology, distinct from that of any other group of Zingiberales, confirms their claim to familial status.
4. Consideration of the conflicting theories proposed to account for the higher chromosome number in genera like Globba, Alpinia, and Phaemeria, etc. leads to rejection of Chakravorti's hypothesis of wholesale fragmentation of chromosomes and the acceptance of the opposed view of Raghavan and Venkatasubban and others.
. Holttum's transference of the genus Zingiber to the tribe Hedychieae has been given cytological support on the following points:
a) the basic number in the genus Zingiber correlates with that of Kaempferia.
) the new tribe Alpinieae (which is infact Zingibereae without Zingiber) have consistently 48 chromosomes in their somatic complements.
. It is suggested that the African representatives of Kaempferia should be given the status of genus; Cienkowskya on the following points:
a) the difference in floral morphology
) geographical separateness and
c) the difference in the number and morphology of the chromosomes. By comparing the present and past findings, various lines of evolution of the chromosome complements within each group are discussed.
. The basic number 11 is considered to be probably the original one for the Zingiberales as a whole, being present in Ravenala which is the most primitive member in the order. From this secondary basic numbers have arisen through evolution.

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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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