Backgrounds: It has been reported that somatic mutations of mitochondrial DNA (mtDNA) is related with aging, or development of cardiovascular disease. We hypothesized that mtDNA4977 deletion mutation (4977-) detected from human blood contributes to atrial dysfunction in patients with . Methods: We studied for mtDNA4977- in 183 patients with non-valvular , (127 PAF, 56 PeAF) and 69 patients with healthy control. The detection of mtDNA4977- was determined by Gene Scan. Results: 1. The mtDNA4977- in patients were older than those without mutation (61.4±.2 vs. 51.8±., p<0.0001). 2. Frequency of mtDNA4977- mutation in patients with ≤45 years old was not different to age matched control (.% vs. 11.%, p=0.2371). . The mtDNA4977- had higher /, (11.±4.8 vs. .1±.1, p=0.0005), plasma levels of TIMP-1 (1.51±0.77 vs. 1.28±0.57 ng/mL, p=0.0210) and ANP (.11±2.67 vs. 1.91±2.01 nmole/L, p=0.0010), and were more frequently taking statin (27.2% vs. .4%, p=0.0055) than those without mutation. 4. .% with mtDNA4977- and 85.5% without mtDNA4977- remain in sinus rhythm 12.±5. months after RFCA (p=0.3008). Conclusion: mtDNA4977- was related with aging, diastolic dysfunction, serologic markers related with atrial remodeling or pressure overloading. Its frequency was not different to age matched patients with control, and did not affect the clinical outcome after RFCA.

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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32.0%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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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-,5α,-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-,5α,-triol (4), -dehydrocholesterol (5) 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, , 5 and did not induce MCT-1 cell ALP activity at 0.1—10 μM. These results suggested that the OH groups at C-5 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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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%; 62,8±4,0%; 79,5±2,%; ,5±2,%; 81,±2,%; 80,±4,4%; for Generic1 - 0; 49,±,%; ,8 ±2,8%; 90,4±,%; , 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,±,%; 66,±8,2%; 76,4±,4%; ,8±5,%; 86,0±,%; 84,±,%: for Generic - 80,8±,%; ,5±1,%; , 8±,2%; ,±2,%; 81,±2,1%; ,1±2,0%; ,0±2,4%; for Generic4 - ,5±1,%; 84,4±0,8%; 84,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,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±0,%; 40, 5±,0%; 62,8±2,0%; 80,0±,1%; 85,4±2,%; ,8±,4%; 80,±,5%; for Generic1 - 0; 67,0±,8%; 89,±2,%; 91, ±4,%; 89,1±1,%; ,±1,4%; 87,8±1,2%; for Generic2 - 0; 42,2±5,%; 75,1±,%; 81,0±,0%; ,4±,2%; , ±1,%; 87,±1,0%; for Generic4 - 85,5±0,5%; 85,±0,5%; 84,±0,%; ,±,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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One method currently being considered for the disposal of high level radio-active waste is burial in the seabed. When a hot object is buried in soil, the temperature of the soil adjacent to the object is raised and there is transient heat flow away from the object. The rise in the temperature of the soil causes excess pore pressures to be generated and transient pore water diffusion also takes place. A finite element formulation of the coupled heat flow and consolidation problem is presented. The computer implementation of this formulation is found to compare favourably with analytical solutions based on the same physical principles.

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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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From the fronds of Polystichum tripteron (KUNZE) P_R. a new norcarotenoid glycoside was isolated and shown to be (R, , R)--hydroxy-megastigma-4, -dien--one--O-β-D-glucoside. The fronds of Dennstaedtia wilfordii (MOORE) CHRIST. contain the same glucoside.

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Two new partially saturated tricyclic ring systems, , a, , 8, , 10, 10a, 11-octahydro-11-oxodibenz [, ] oxepins (a and ), and -thiepins (4a and 4) were synthesized. Compounds 4a and 4 were desulfurized to give a pair of isomeric 2-methylbenzoylcyclohexanes (10a and 10). Deuterated 4a and 4 (11a and 11) were prepared starting from butadiene- (12). The stereochemical features of a (trans), (cis), 4a (trans) and 4 (cis) are compared with those of 10a, 10, 11a and 11 on the basis of proton nuclear magnetic resonance data.

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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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In Japan, aseptic meningitis cases due to enterovirus infections increase every summer in various degrees with an incidence peak usually in July. During the past 11 years from 1981 through 1991, a total of 8, 595 enterovirus isolations from aseptic meningitis cases were reported from 54 participating laboratories. Eight enterovirus types caused large epidemics; more than 100 isolations of each type from aseptic meningitis cases were reported for every epidemic year of the respective type. They were coxsackievirus (C) types and 5, echovirus () types 4, , , , 18 and 30. Among these, the highest meningitisassociating frequency was reported for 30, representing .% of the total isolations reported for the type during this period, followed by 4, 71.1%. The frequencies of , , and CB5 were in a range from 54.5% to 44.4%, while that of 18 was 37.% and that of CB 21.0%. During the epidemics, enterovirusassociated meningitis was most frequently reported among children of 4- years of age. High frequencies were also shown in infants less than 1-year of age in some types. A total of 4, 240 enteroviruses were isolated from cerebrospinal fluid of aseptic meningitis cases, representing 49.% of the cases with enterovirus isolation.

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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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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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11-Amino-, a, , 8, , 10, 10a, 11-octahydrodibebenzo[, ]thiepines (a-d) and -oxepines (a-d) were synthesized by the Leuckart reaction of , a, , 8, , 10, 10a, 11-octahydro-11-oxodibenzo[, ]thiepines (1a, )and -oxepines (2a, ) followed by hydrolysis of the reaction products 4a-d and 5a-d, respectively. The four diastereomers, cis(a-H, 10a-H)-cis(10a-H, 11-H) a and a, cis(a-H, 10a-H)-trans(10a-H, 11-H) and , trans(a-H, 10a-H)-trans(10a-H, 11a-H)c and c, and trans(a-H, 10a-H)-cis(10a-H, 11-H) d and d, were isolated and their configurations and conformations were elucidated by chemical methods together with ¹H-nuclear magnetic resonance spectroscopic and X-ray crystallographic analyses.

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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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A biosynthetic pathway for (

)-methyl cinnamate formation was evaluated in Tricholoma matsutake by tracer experiments using ¹³C- and ²H-labeled precursors. One hundred percent selective ¹³C incorporation was observed when L-[1,2,,4,5,,,8,-

13C₉

, ^15/N]phenylalanine was converted to (

E

)-[1,2,

3

,4,5,

6

,

7

,8,

9

-

13C₉

]cinnamate and (

E

)-[1,2,

3

,4,5,

6

,

7

,8,

9

-

13C₉

]methyl cinnamate. Similarly, 100% selective ¹³C incorporation was observed when (

E

)-[1,2,

3

,4,5,

6

,

7

,8,

9

-

13C₉

]cinnamate was converted to (

E

)-[1,2,

3

,4,5,

6

,

7

,8,

9

-

13C₉

]methyl cinnamate. In contrast, the ²H incorporation selectivities were

82

.1% and 81.4% when L-[2,

3

,4,5,

6

,

7

,

7

,8-²H₈]phenylalanine was converted to (

E

)-[2,

3

,4,5,

6

,

7

,8-

2H₇

]cinnamate and (

E

)-[2,

3

,4,5,

6

,

7

,8-

2H₇

]methyl cinnamate, respectively. Thus, T. matsutake synthesizes (

E

)-methyl cinnamate from L-phenylalanine via (

E

)-cinnamate. (

E

)-cinnamate was likely formed through two pathways: one was major and the other was a minor.

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