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.±.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 (7.% vs. 11.6%, p=0.2371). . The mtDNA4977- had higher /, (11.±.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. .%, p=0.0055) than those without mutation. . .% with mtDNA4977- and 85.5% without mtDNA4977- remain in sinus rhythm 12.7±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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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-7,-diene-,5α,6β-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,6β-triol (), 7-dehydrocholesterol (5) and cholecalciferol (6) were tested. The enzyme activities of MCT-1 cells were increased .0-fold by 10 μM 1 and 2.-fold by 10 μM . However, 2, , 5 and 6 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-6 of 1 and 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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The high-power reconnection heating of spherical tokamak (ST) has been studied in the TS- experiment by use of axial merging of two STs. In this method, the merging/ magnetic reconnection transformed a part of magnetic energy of merging STs into their thermal energy within short reconnection time. Our present low-field merging (0.-0.5kG, R-0.2m) attained the maximum heating power of -10MW and increased the beta-values of STs by factor 2- transiently. The ion heating energy was found to increase inversely with the q-value (B_t component) of two STs. The most probable cause for this dependence is fast reconnection speed/ outflow speed due to large anomalous resistivity of current sheet in low-q state. After merging startup, decrease in beta was observed especially in low-q STs, indicating that the final beta value of ST increased with the q-value.

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The association between apolipoprotein (Apo-) polymorphism and the response of plasma cholesterol to dietary therapy (cholesterol intake of less than 300mg/day) was investigated for about 8 weeks in 208 nonfamilial hypercholesterolemia patients (/ 161, / 47). The baseline lipoprotein concentration and the intake of energy and lipids were not significantly different between subjects with / and those with / phenotypes. After the dietary therapy plasma total cholesterol and low density lipoprotein cholesterol were significantly decreased in both phenotype groups (p<0.05). The patients with / had significantly smaller reductions of LDL-C than the patients with /. The changes of LDL-C showed a significant difference between the patients with / and / by the Kruskal Wallis test (p=0.041). The presence of / predicted the degree of cholesterol reduction following dietary therapy.

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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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Chemical synthesis of (, 24R)- and (, 24S)-1, 24-dihydroxy--vitamin has been achieved starting with the commercially available dinorcholenic acid acetate. Synthesis involved introduction of the 1-hydroxy group by a reduction of the 1, 2-epoxide generated by epoxidation of the 1, , 6-trien--one. The side chain on the steroid was then constructed by means of a Wittig reaction followed by introduction of the Δ⁷ bond by standard methods and its protection with 1-phenyl-1, 2, -triazoline-, 5-dione. Subsequent reduction of the hydroxy groups in the steroid side chain followed by reduction of the Diels-Alder addition products yielded the both 24-isomers. The 5, 7-dienes were irradiated and the corresponding vitamin D compounds isolated. Nuclear magnetic resonance was used to identify individual isomers. The (, 24S)-1, 24-hydroxyvitamin compound bound equally well to the chick intestinal cytosol receptor as 1, 25-dihydroxyvitamin , while the 24R-isomer was approximately ten times less active. In vivo, both isomers were less active than 1, 25-dihydroxyvitamin ; however, the 24S-isomer was considerably more active than the 24R-isomer approaching the activity of 1, 25-dihydroxyvitamin .

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Effect of an antirheumatic gold compound, Auranofin (

), have been revealed.  1-10 µM of inhibited prostaglandin (PGE₂) production and nitric oxide (NO) production in macrophages treated with some stimulatory compounds.  We found that reduced cyclooxygenase (COX)-2 and inducible NO synthase (iNOS) mRNA levels, but not affected their enzyme activities.  We then revealed that partly inhibited the nuclear-translocation of NF-κB while PGE₂ production was almost completely inhibited.

  In the review on manuscripts,

is reported to down-regulate the mRNA levels of SLC47A1, , , ABCG2, SLCO1B1, , and up-regulate the mRNA levels of , ABCB1, , ABCC2, SLC31A2, CLTD, CLTB.  PGs are known to be transported by transporters, OATP-PG (SLCA), SLC21A2 (OATP2A1, SLCO2), SLC21A11 (OATPA1), and ABCC, though I could not identify whether reduced PGE₂ concentration in cellular cultured medium as described above via these transporters by downregulation for export of PGE₂.

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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;

;) was performed. At first, we moved drugs from solution with pH 1.2 (1.2±0.05) to pH 7.0 (7.0±0.05) and measure concentration of omeprazole in solution by high-performance liquid chromatography. According to our self-developed formula, pH 7 exposure time of resistance to PDGR for omeprazole is minutes, i.. the active substance should not be released within minutes at pH 7. The exposure at the second stage was conducted with pH (.0±0.05), that imitated gastric pH after PPI administration. And then we also moved drugs to pH 7 with the subsequent measurement of omeprazole concentration.

Results

Omeprazole concentrations after

, 10, 15, 20, 30, 45, 60 minutes in pH 7 solution at the first stage were different for OO and generics. For OO, these values were ,7±0,7%; 41,±,0%; 62,8±,0%; 79,5±2,%; ,5±2,%; 81,6±2,%; 80,6±,%; for Generic1 - 0; 49,±,%; 88,8 ±2,8%; 90,±,7%; 88, 2±2,2%; 87,±2,0%; 85,±1,1%; for Generic2 - 0; 30,6±6,%; 66,7±8,2%; 76,±7,%; ,8±5,%; 86,0±,7%; 84,6±,%: for Generic - 80,8±,6%; ,5±1,%; , 8±,2%; ,±2,7%; 81,±2,1%; ,1±2,0%; ,0±2,%; for Generic - ,5±1,7%; 84,±0,8%; 84,2±1,2%; , ±0,%; ,±0,%; ,±0,%; ,8±1,1%, respectively.

An analysis of the omeprazole concentration in pH 7 solution at the second stage revealed the following parameters after the same time: for OO -

,±0,6%; 40, 5±,0%; 62,8±2,0%; 80,0±,1%; 85,±2,%; ,8±,%; 80,±,5%; for Generic1 - 0; 67,0±7,8%; 89,7±2,%; 91, ±,%; 89,1±1,6%; 88,±1,%; 87,8±1,2%; for Generic2 - 0; 42,2±5,6%; 75,1±7,%; 81,0±6,0%; 88,±,2%; 88, 6±1,%; 87,±1,0%; for Generic - 85,5±0,5%; 85,6±0,5%; 84,7±0,%; ,7±,0%; 84,±0,%; 84,±0,%; 84,±0,%, respectively. Generic release and degradation were completely realized at pH .

Conclusion

Decreased gastric stability of Generic

and Generic 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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The leaning tower of Pisa is a famous historical structure, especially in the field of soil mechanics. In this paper, the historical development of the inclination is reconstructed considering that a ground failure took place after each of the three construction phases. Model tests (scale 1 : 130) were carried out in order to predict that the tower will fail definitely, i.. without any further disturbances, at an angle of inclination of 5.7°, which is dramatically close to the actual value of 5.5°. The estimated probability of failure rises very quickly with an increase in the angle of inclination. Conservation of the tower should be done therefore with utmost caution.

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The performance of single pitch and multi pitch screw anchors during the application of installation torque is presented. An experimental testing program was conducted using five models of screw anchors with different geometry. The effect of the shape of the screw element, sand properties, and installation depth on the required installation torque value was examined. A theoretical model was developed from which the required installation torque value can be calculated in terms of the influencing factors. The required installation torque can be determined in terms of the ultimate uplift resistance calculated from any of the available theories. Based on the actual installation torque value measured in the field, the anticipated pullout capacity can be back calculated from the present theory. A comparison between theoretical and experimental results showed good agreement. Also, good agreement was observed when the present theoretical results were compared with the available field results reported in the literature.

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Results of model loading tests on dense sand were reviewed to assess the variation in bearing capacity factors N_γ and N_q relative to the width of the foundation base. Consequently, it is confirmed that N_γ decreases non-linearly with increase in the width of foundation base and that N_q decreases more sharply than N_γ does as the width increase. It is also found that N_q decreases as the ratio of burried depth to the width increase. The cause of decrease in N_γ or N_q with increase in the width is regarded to be the rise of stress level which induces lowering of the angle of internal friction φ and volume reduction in the bearing sand by compression.

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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, b) 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.
. 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.
5. 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.
b) the new tribe Alpinieae (which is infact Zingibereae without Zingiber) have consistently 48 chromosomes in their somatic complements.
6. 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
b) 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.
7. 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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Two new vitamin analogues, 1α-hydroxy-24, 24-dimethyl--dehydrovitamin (13) and 1α, 25-dihydroxy-24, 24-dimethyl--dehydrovitamin (17), which are blocked for 24-hydroxylation by the methyl groups, were synthesized from 1α, -bismethoxymethoxypregn-5-ene-20Scarbaldehyde (6) by using the orthoester Claisen rearrangement for construction of the carbon skeleton of their side chains. These compounds (13 and 17) elicited a rise in serum calcium, but not in serum inorganic phosphorus in rats. In a bioassay for alkaline phosphatase, they were found to show much weaker activity than 1α-hydroxy vitamin (5).

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1, an ets-oncogene family transcription factor, has been shown to upregulate transcription from matrix metalloproteinase (MMP) genes, which confers the invasive phenotype on cancer cells. On the other hand, we have demonstrated by luciferase assay that 1 positively regulates transcription from the p21^waf1/cip1 promoter. Ca. cells were transfected with a metallothionein-inducible 1 expression vector (Ca.MTF) to investigate the relationship between invasive ability and cell cycle modulation caused by 1. MMP- and p21^waf1/cip1 protein were synergistically increased in the ZnCl₂ stimulated CA.MTF cells, and both proteins were identified in the same cells when 1 was induced. These results imply that invasive growth of tumor cells occurs in the static state of the cell cycle and that 1 plays a key role in this phenomenon.

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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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