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31.
32.
SB Christensen A Guider CJ Forster JG Gleason PE Bender JM Karpinski WE DeWolf MS Barnette DC Underwood DE Griswold LB Cieslinski M Burman S Bochnowicz RR Osborn CD Manning M Grous LM Hillegas JO Bartus MD Ryan DS Eggleston RC Haltiwanger TJ Torphy 《Canadian Metallurgical Quarterly》1998,41(6):821-835
Evaluation of a variety of PDE4 inhibitors in a series of cellular and in vivo assays suggested a strategy to improve the therapeutic index of PDE4 inhibitors by increasing their selectivity for the ability to inhibit PDE4 catalytic activity versus the ability to compete for high affinity [3H]rolipram-binding sites in the central nervous system. Use of this strategy led ultimately to the identification of cis-4-cyano-4-[3-(cyclopentyloxy)-4-methoxyphenyl]cyclohexane-1-carboxyl ic acid (1, SB 207499, Ariflo), a potent second-generation inhibitor of PDE4 with a decreased potential for side effects versus the archetypic first generation inhibitor, (R)-rolipram. 相似文献
33.
This paper describes a technique for the automatic adaptation of a canonical facial model to data obtained by a 3D laser scanner. The facial model is a B-spline surface with 13×16 control points. We introduce a technique by which this canonical model is fit to the scanned data and that takes into consideration the requirements for the animation of facial expressions. The animation of facial expressions is based on the facial action coding system (FACS). Using B-splines in combination with FACS, we automatically create the impression of a moving skin. To increase the realism of the animation we map textural information onto the B-spline surface. 相似文献
34.
R Briesewitz A Kern LB Smilenov FS David EE Marcantonio 《Canadian Metallurgical Quarterly》1996,7(10):1499-1509
Localization of integrin receptors to focal contact sites occurs upon ligand binding. This activity is latent, since unoccupied integrin receptors do not localize to focal contacts. Deletion analysis has revealed that the alpha cytoplasmic domains is required for the maintenance of integrin receptor latency. Our current hypothesis for the mechanism of integrin post-ligand binding events is that there is a change in relationship of alpha and beta cytoplasmic domains, which overcomes receptor latency. One possible mechanism for such a change would involve the amino acid residues at the membrane-cytoplasm interface. To test this hypothesis, we have produced point mutations in the human integrin alpha 1 subunit. These mutations had no effect on the adhesion via alpha 1 beta 1 to its ligand, collagen IV. However, receptor latency is lost in one of these mutants, leading to constitutive focal contact localization. This effect did not occur in receptors with an exchange of intracellular domains, suggesting that the mechanism of loss of latency involves a relative motion of the integrin chains. These results suggest a model in which post-ligand binding events in integrin receptors are associated with changes in the position of the alpha and beta cytoplasmic domains. 相似文献
35.
LB Bunyard LI Katzel MJ Busby-Whitehead Z Wu AP Goldberg 《Canadian Metallurgical Quarterly》1998,68(5):1136-1142
BACKGROUND: Energy requirements for weight maintenance decrease with age. Often, this decline is not proportionately matched by reduced energy intake, resulting in weight gain. OBJECTIVE: We hypothesized that energy requirements for total daily weight maintenance in healthy, sedentary, middle-aged men would increase after regular aerobic exercise or aerobic exercise plus weight loss to levels comparable with those in middle-aged athletes. DESIGN: Weight-maintenance energy requirements were determined during weight stability (+/- 0.25 kg) in 14 lean, sedentary (LS) men; 18 obese, sedentary (OS) men; and 10 male athletes of comparable ages (x +/- SEM: 58 +/- 1 y). Studies were done at baseline and after 6 mo of aerobic exercise (LS men) or aerobic exercise plus weight loss (OS men) or 3 mo of deconditioning (athletes). RESULTS: The interventions raised maximal oxygen uptake (VO2max) by 15% in the LS men and by 13% in the OS men and decreased it by 14% in athletes (all P < 0.01), eliminating the differences among groups at baseline. Body fat was reduced significantly in LS and OS men; fat-free mass decreased in OS men. Average daily energy requirements increased by 8% in LS men and by 5% in OS men (both P < 0.01) to levels comparable with the baseline requirements of athletes and correlated with VO2max (r2 = 0.22, P < 0.0001) and fat-free mass (r2 = 0.05, P < 0.02) across the range of VO2max achieved by all subjects. CONCLUSIONS: Under free-living conditions, aerobic exercise eliminated the difference in weight-maintenance energy requirements between middle-aged sedentary and athletic men, suggesting that energy requirements of healthy, middle-aged men are modifiable by regular physical activity. 相似文献
36.
Acute effects of nifedipine in renal transplant recipients treated with cyclosporine or azathioprine
LB Hilbrands AJ Hoitsma HW van Hamersvelt JF Wetzels FT Huysmans RA Koene 《Canadian Metallurgical Quarterly》1994,24(5):838-845
Cyclosporine (CsA) impairs renal function, probably by preglomerular vasoconstriction. Vasodilating substances may therefore be of benefit to ameliorate CsA-induced renal dysfunction. We studied the acute effects on blood pressure and renal function of the dihydropyridine calcium antagonist nifedipine (10 mg orally) in 20 CsA-treated renal transplant patients. In addition, we compared the effects of nifedipine when given immediately before and 4 weeks after elective conversion from CsA to azathioprine. Compared with placebo (n = 14), administration of nifedipine led to a significant decrease in blood pressure and a strong natriuretic and diuretic response. Despite the reduction in blood pressure, glomerular filtration rate improved from 60 +/- 20 (mean +/- SD) to 69 +/- 24 mL/min/1.73 m2 (P < 0.001) and renal plasma flow (RPF) increased from 260 +/- 87 to 338 +/- 120 mL/min/1.73 m2 (P < 0.001). The combination of a decreased blood pressure with an increased RPF was reflected in a sharp decrease in renal vascular resistance (0.34 +/- 0.18 units v 0.23 +/- 0.10 units; P < 0.001). The conversion from CsA to azathioprine by itself led to significant increases in glomerular filtration rate (62 +/- 15 mL/min/1.73 m2 v 76 +/- 18 mL/min/1.73 m2; P < 0.05) and RPF (280 +/- 86 mL/min/1.73 m2 v 334 +/- 66 mL/min/1.73 m2; P < 0.05). During treatment with azathioprine an effect of nifedipine on glomerular filtration rate and RPF was no longer observed, although the natriuretic effect was similar on both occasions. The decrease in renal vascular resistance was larger during treatment with CsA than during treatment with azathioprine (P < 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
37.
The corrosion of refractory ceramic materials in the plasma of combustion gases The paper describes the testing of the corrosion resistance of refractory ceramics based on Al2O2, MgO and ZrO2, as well as of phosphate cements, in flowing ionized gases as are present in the cornbustion products of conventional combustibles. A qualitative interpretation of the corrosion phenomena has been obtained experimentally using known test conditions and available thermodynamic and chechemical data. 相似文献
38.
A new experimental technique for the determination of thermodynamic activity of alloys has been developed utilizing a triple Knudsen cell with a pure enriched natural isotope as the standard reference state. The alloy for which activity is to be determined is placed in one of the two effusion chambers of the triple cell and the pure isotopic standard in the other. The molecular beams from each chamber effuse into a third upper chamber and through a collimating hole into the ion source of a Bendix time-of-flight mass spectrometer. Since the recorded intensities are proportional to the vapor pressures within the chambers, a simple calculation based upon their ratio gives a direct determination of the activity of the solute in the alloy. The accuracy of the triple cell technique for the experimental determination of activities was checked by the measurement of the copper activity in a Ni?Cu alloy containing 30.6 wt pct Cu. A value ofRT γCu=1778±142 cal per g-atom at 1450°K was obtained, which is in excellent agreement with values in the literature. The activity of copper in the bcc β phase when then determined for four Ti?Cu alloys (X Cu=0.033 to 0.085), using pure enriched Cu65 as the standard reference state. The composition range investigated was limited to alloys belowX Cu=0.10, the maximum solubility within the experimental temperature range between 1423° and 1573°K, the activity of copper in the bcc β phase can be expressed using pure liquid copper as the standard state by the following equation:RT Ina Cu=RT InX Cu+X Ti 2 (1.92±0.30) in kcal per g-atom. The activity of titanium is given byRT Ina Ti=RT InX Ti+X Cu 2 (1.92±0.30) in kcal per g-atom. 相似文献
39.
40.
Five cases of congenital contractural arachnodactyly (CCA) are reported. Three belong to the one family. CCA has often been mistaken for Marfan's disease and arthrogrypois multiplex. Because CCA has a more favourable prognosis, it is very important to be able to recognize this syndrome. 相似文献