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 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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From the fronds of Polystichum tripteron (KUNZE) P_R. a new norcarotenoid glycoside was isolated and shown to be (6R, , R)--hydroxy-megastigma-, -dien-3-one--O-β-D-glucoside. The fronds of Dennstaedtia wilfordii (MOORE) CHRIST. contain the same glucoside.

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Repetitive liquefactions in angular and subangular gravels from an alluvial fan, in the case of two earthquakes with accelerations lower than that of a former which had caused liquefaction some months before, are described. The liquefaction took place from the surface, down to a depth of approximately 10 m. Water laden with sediments spouted out for some tens of minutes after the strong motion ceased. Knowledge of the grain size distribution of the sediments inside the body of the alluvial fan roughly defines the areas of the fan prone to future liquefaction. Non-repetitive liquefaction in overconsolidated fine fluvio-lacustrine sand of glacial origin at the unusual depth of 14 m to 16 m is also described. From the observation of sand lifted up for 10 m inside a large diameter well, and of that which spouted out from several microvents, it was estimated that extra-pore pressure was close to lithostatic conditions. Nevertheless, modeling of intrinsic pore pressure buildup on the DESRA programme gives lower values than the experimental one. Geotechnical characteristics of the 12 m-thick sandy stratum indicate that the upper part is unusually soft, either due to water circulation or past repetitive liquefactions which prevented reconsolidation. It is suggested that excess pore pressure generated by the earthquake was also due to redistribution of pressure from adjacent sediments.

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 The stability of

‒tetrahydrocannabinol acetate (‒THC‒OAc) and ‒tetrahydrocannabinol acetate (‒THC‒OAc) in -liquid during storage was investigated. ‒THC‒OAc liquids in cartridges were stored at 80℃ or 30℃ for 28 days. The relative concentrations of cannabinoids in the liquids were measured by gas chromatography with flame ionization detection. ‒THC‒OAc decreased during storage at either temperature. ‒THC, a minor impurity, also decreased. ‒THC‒OAc liquid in a cartridge was stored at 80℃ for 57 days. The concentration of ‒THC‒OAc and ‒THC, a minor impurity, did not change during that time. Cannabinol acetate increased in all liquids, and unknown products were also detected by gas chromatography/mass spectrometry (GC/MS). The ‒THC‒OAc and ‒THC‒OAc liquids were subjected to GC/MS to detect representative diluents, glycerol, propylene glycol, and polyethylene glycol 400, but none of these were detected.

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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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Backgrounds: We evaluated that electrophysiological characteristics and clinical outcomes of atrial fibrillation () with sinus node dysfunction (SND) after radiofrequency catheter ablation (RFCA). Methods: Among 428 patients (male, 77.3%; 56.0±11.0 years old; paroxysmal , 69.%) who underwent RFCA for , 50 patients (11.%) who had ECG documented symptomatic SND (28 Tachybrady (T-Bs) and sick sinus syndrome; SSS) were compared with 378 patients without SND. Results: 1. The patients with SND were older (60.3±61617; . vs. 55.±61617; 11.1 years, p=0.003) and had higher /′ (12.±61617; 5.1 vs. .±61617; .1, p=0.002) than those without SND. . Effective refractory period (ERP) at high right atrium (RA) was longer (ERP; 244.1±61617; 26.1 vs. 232.±61617; 28. ms, p=0.033) and endocardial voltage at posterior left atrium (LA) was higher (1.±61617; 0. vs. 0.±61617; 0. mV, p=0.041) in patients with SND than those without it. 3. The recurrence rate was not different significantly between groups (28.0% vs. 20.0%, p=0.623) during 12.±5. months. A patient with SSS (.5%) and a patient with T-Bs (3.6%) were implanted pacemaker because of recurrent symptomatic bradycardia after RFCA. Conclusion: is associated with SND more often in patients with old age, diastolic dysfunction, and high RA ERP. RFCA results in comparable clinical outcome in those patients, but % of them required pacemaker implantation due to recurrence and symptomatic bradycardia.

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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.±. vs. 51.±., p<0.0001). . Frequency of mtDNA4977- mutation in patients with ≤45 years old was not different to age matched control (.3% vs. 11.6%, p=0.2371). 3. The mtDNA4977- had higher /, (11.3±. vs. .1±3.1, p=0.0005), plasma levels of TIMP-1 (1.51±0.77 vs. 1.28±0.57 ng/mL, p=0.0210) and ANP (3.11±.67 vs. 1.91±.01 nmole/L, p=0.0010), and were more frequently taking statin (27.% vs. .%, p=0.0055) than those without mutation. . 82.3% 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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Chemical properties of ergosta-, 6, (14), -tetraen-3-one (1) were investigated. Though 1 is rather stable to acids or bases, it reacts easily with two moleculres of oxygen on irradiation with UV light to give 6α, -epidioxy-14α-hydroperoxyergosta-, , -trien-3-one (), which is transformed successively to 6α, ;, -diepoxy-14α-hydroperoxyergosta-, -dien-3-one (3) and 14α-hydroperoxy--hydroxyergosta-, , -triene-3, 6-dione () under these reaction conditions.

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 We examined the stability of

-tetrahydrocannabinol acetate (-THC-OAc) and -tetrahydrocannabinol acetate (-THC-OAc) in -liquid products. Eight samples were heated at 30℃ for 28 days and one of them was heated at 70℃ for , , , 10, and 15 days. Residual ratios of -THC-OAc and -THC-OAc were evaluated by gas chromatography with flame ion detection and their degradation products were examined by gas chromatography/mass spectrometry (GC/MS). Some samples were tested for solubility in hexane and were submitted to GC/MS analysis to detect propylene glycol and glycerol. After a 28-day incubation at 30℃, -THC-OAc was slightly decomposed (residual ratio: 84.5–94.%) but -THC-OAc was almost stable (residual ratio: 95.–108.%). Heating at 70℃ decomposed not only -THC-OAc but also -THC-OAc. The decomposition proceeded rapidly in the initial days then slowly until 15 days later. The degradation products, four putative one-oxygen-atom adducts and cannabinol, were detected but deacetylated products (-tetrahydrocannabinol and -tetrahydrocannabinol) were not detected. All the samples tested were completely dissolved in hexane differently from propylene glycol and glycerol. Propylene glycol and glycerol were not detected from the samples completely dissolved in hexane. This study indicated that deacetylation of -THC-OAc and -THC-OAc did not proceed when the sample did not contain propylene glycol and glycerol.

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Tumor-infiltrating lymphocytes (TIL) were tested for cytotoxicity against autologous tumor cells in a study utilizing a chemically induced cancer ofthe bladder (transitional cell carcinoma), -47, in inbred ACI/N rats. From tumors grown after subcutaneous implantation of -47 in the rats TIL were separated by density gradient centrifugation and incubated in plastic dishes for separation of non-adherent from adherent cells. The non-adherent cells were further fractionated into T and B cells by the panning method using anti-rat (ab')

2

antibody. The cell fractions were each added to

BC

-47 in culture to be assessed for antitumor effect by the crystal violet dye exclusion method and 3H-thymidine incorporation inhibition assay. Peripheral blood mononuclear cells (PBMC) were also tested as described above. TIL expressed significantly higher cytotoxicity against

BC

-47 with the mean % cytotoxicity of 56.6±5.6% and 87.5±

7

.1% at

E

/T ratios of 10:1 and 20:1, respectively, as compared to PBMC(

9

.

9

±5.0% at

E

/T 10:1) (P<0.001). The adherent cells, B and T cell fractions showed respective % cytotoxicity of 92.

4

±

2

.

8

%, 57.

9

±10.6% and

9

.

9

±

7

.

8

% at an

E

/T ratio of 10:1. TIL pretreated with IFN or rIL-

2

for 24or 48 hours did not exhibit any noticeably enhanced antitumor activity at an

E

/T ratio of 5:1. Prevention of direct contact of

BC

-47 cells and TIL by an interposed Millipore membrane (0.45μm) resulted in an unequivocal reduction of antitumor effect. This finding clearly indicates that the direct contact with

BC

-47cells and TIL is necessary for TIL to manifest their cytotoxicity against the autologous tumor cells, suggesting that TIL exhibit autologous tumor killing activity through cell-mediated cytotoxicity.

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Stereoselective synthesis of , - and , Z-β-ionylideneacetaldehydes was accomplished from the β-ionone tricarbonyl iron complex, and the latter was converted to Z-retinoic acid.

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The small strain stiffness and anisotropic nature of two sands with different geological origin have been determined via laboratory seismic tests performed in a triaxial cell. Dry triaxial reconstituted specimens of Ticino river silica sand (TS) and of Kenya carbonatic sand (KS) were subjected to isotropic and anisotropic states of effective stress ; then both shear and constrained compression waves were propagated in vertical, horizontal and oblique directions by means of five couples of piezoelectric transducers especially arranged in the specimens. The propagated compression and shear waves allow the assessment of the constrained M₀ and shear G₀ moduli respectively, at very small strains where, as a first approximation many soils can be assumed, from an engineering point of view, to behave as an elastic cross-anisotropic medium with a vertical axis of symmetry. This paper, after a brief description of the novel measuring technique adopted and of the tested materials, summarises the test results and their interpretation in order to separate the effects of the fabric anisotropy from those produced by the state of effective stresses on soil stiffness. The stiffness and anisotropic response of the two tested sands are compared. Finally the results enable us to establish five independent constants of the cross-anisotropic elasticity model, which appears to be appropriate to reproduce the behaviour at small strain of the two sands.

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Four new sterols, 5α, 6α-epoxy-(, 24R)-ergosta-(14), -diene-3β, -diol (1), (, 24R)-ergosta-, -diene-3β, 5α, 6β, -tetrol (), (, 24R)-ergosta-, (11), -triene-3β, 5α, 6β-triol (3) and 3β, 5α, 6β-trihydroxy-(, 24R)-ergost--en--one (), have been isolated from the fruit bodies of Grifola frondosa (FR.) S. . GRAY (Polyporaceae)together with fourteen known ones (5-18), of which two (5 and 6) are reported for the first time from a natural source. The structures of these compounds were elucidated on the basis of spectral data.

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Eight new sterols, 5α, -epidioxy-(, 24R)-23-methylergosta-6, -dien-3β-ol (1), 3β, 5α, -trihydroxy-(, 24R)-23-methylergosta-, -dien-6-one (), 3β, 5α, -trihydroxy-(24S)-ergost--en-6-one (3), 3β, 5α, , 14α-tetrahydroxy-(, 24R)-ergosta-, -dien-6-one (), (, 24R)-ergosta-, -diene-3β, 5α, 6α, -tetrol (5), 5α, -epidioxy-3β-hydroxy-(, 24R)-ergosta-, -dien-6-one (6), 5α, -epidioxy-3β-hydroxy-(24S)-ergost--en-6-one () and 5α, 6α-epoxy-(, 24R)-ergosta-, -diene-3β, , 14α-triol (), have been isolated from five edible mushrooms, Lentinus edodes, Flammulina velutipes, Hypsizigus marmoreus, Pleurotus ostreatus and Pholiota nameko together with fifteen known ones (-23), of which two (16 and 17) are reported for the first time from a fungal source. The structures of these new compounds were elucidated on the basis of their spectral data.

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