The theoretical formulas of the fluorescent x-ray intensity (the primary, the secondary and the tertiary fluorescent x-rays) are obtained and actual calculations are made for nickel-iron, iron-chromium, and nickel-iron-chromium alloys. In the calculation, the continuous intensity distribution of the irradiating x-rays for the wavelength is taken into account. The theoretical results agree with the experiments very well, the deviations being 1% at most, and it is concluded that the theoretical estimation of the fluorescent x-ray intensity emitted from samples of various composition is possible. The matrix effect, absorption effect, and enhancement effect are evaluated from the present theory. In the enhancement effect, secondary fluorescent x-rays are quite significant (for instance, the chromium secondary fluorescent x-rays from Cr 2% and Fe 98% alloy reach the 55% of the chromium primary fluorescent x-rays and they can not be neglected), but the tertiary fluorescent x-rays are only a few per cent. The usual approximation methods, where the irradiating x-rays are assumed as monochromatic rays and the secondary fluorescent rays are not taken into consideration are also discussed and their meaning is made clear.
Pancreatic cancer is frequently associated with intense growth of fibrous tissue at the periphery of tumours, but the histopathological quantification of this stromal reaction has not yet been used as a prognostic factor because of the difficulty of obtaining quantitative measures using manual methods. Manual histological grading is a poor indicator of outcome in this type of cancer and there is a clinical need to establish a more sensitive indicator. Recent pancreatic tumour biology research has focused upon the stromal reaction and there is an indication that its histopathological quantification may lead to a new prognostic indicator.Histological samples from 21 cases of pancreatic carcinoma were stained using the sirius red, light-green method. Multiple images from the centre and periphery of each tumour were automatically segmented using colour cluster analysis to subdivide each image into representative colours. These were classified manually as stroma, cell cytoplasm or lumen in order to measure the area of each component in each image. Measured areas were analysed to determine whether the technique could detect spatial differences in the area of each tissue component over all samples, and within individual samples.Over all 21 cases, the area of stromal tissue at the periphery of the tumours exceeded that at the centre by an average of 10.0 percentage points (P < 0.001). Within individual tumours, the algorithm was able to detect significantly more stroma (P < 0.05) at the periphery than the centre in 11 cases, whilst none of the remaining cases had significantly more stromal tissue at the centre than the periphery.The results demonstrate that semi-automated analysis can be used to detect spatial differences in the area of fibrous tissue in routinely stained sections of pancreatic cancer.
This article is available online at http://dmd.aspetjournals.org ABSTRACT:The ratio of drug levels in cerebrospinal fluid (CSF) to plasma (CSF/plasma) at equilibrium has been viewed as in vivo free fraction (fp) in plasma [CSF/plasma ؍ fp], if no active transport is involved in brain penetration. We determined the CSF/plasma level following oral administration in rats and in vitro rat plasma protein binding for 20 compounds that were synthesized in our institute and have similar physicochemical properties. However, results indicated that the CSF/plasma was not only poorly correlated with fp but remarkably lower than fp in most of the compounds tested, suggesting that certain transporters such as P-glycoprotein (P-gp) located in blood-brain barrier (BBB) may decrease the unbound drug concentration in the brain. We evaluated P-gp-mediated transport activity of the 20 compounds with P-gp (mdr1a)-transfected LLC-PK1 cells and calculated P-gp efflux index (PEI), indicating the extent of P-gp-mediated transport. A plot of the CSF/ plasma versus fp/PEI showed a strong correlation (r ؍ 0.93), and the absolute values were almost identical [CSF/plasma ؍ fp/PEI]. These results suggest that P-gp quantitatively shifts the equilibrium of unbound drugs across the BBB. Although we cannot rule out the possibility that endogenous transporters other than P-gp on BBB and/or blood-CSF barrier may affect CSF levels of compounds, the present study indicated that fp and PEI measurements may be useful in predicting in vivo CSF/plasma fractions for central nervous system-targeting drugs.Since cerebrospinal fluid (CSF 1 ) is a very low protein fluid, and drug in CSF is considered to be almost unbound, the ratio of drug concentration in CSF to plasma (CSF/plasma) in an equilibrium state has been viewed as in vivo free fraction in plasma (fp) (CSF/plasma ϭ fp), if no active transport is involved in brain penetration (Lin and Lu, 1997).Consistent with this notion, it has been reported that the in vitro free fraction of phenytoin in serum (0.155) is almost equal to the CSF/serum drug ratio (0.185) (Chou and Levy, 1981), and the in vitro fp of demethylchlorimipramine (0.035) is similar to the CSF/plasma ratio (0.026) (Bertilsson et al., 1979). Furthermore, equilibrium CSF/plasma ratios of eight benzodiazepines are known to be highly correlated with fp (r ϭ 0.93, regression line slope ϭ 0.98) (Arendt et al., 1983). These results suggest that in vitro fp may accurately reflect CSF/plasma. However, CSF/plasma can be lower than fp, if certain active transporters such as P-glycoprotein (P-gp) are involved in brain penetration. P-gp is an ATP-dependent efflux pump that transports a variety of amphiphilic and hydrophobic drugs and plays a major role in multidrug resistance in cancer cells. P-gp is also expressed in normal tissues, including the apical membranes of intestinal and renal epithelia and the endothelial cells of the blood-brain barrier. The putative function of P-gp in normal tissues is to act as a functional barrier for endogen...
Dependence of the leakage current of Si N+P diodes on the surface metal (Cu, Ni or Fe) concentration after quantitative contamination was investigated, and the causes of the leakage current were studied by SIMS, TEM and optical microscopy. Cu was gettered in the N+ area, forming many large dislocations in the N+ area and inducing some dislocations in the substrate near the junction; thus, the leakage current increased remarkably. Ni was gettered in the N+ area also, but did not form large dislocations, so the leakage current did not increase. Fe was not gettered easily, and hence the leakage current increased corresponding to the Fe concentration.
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