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Multimedia Tools and Applications - Discovering the relevant web services for specific applications in the dynamically changing business world becomes very critical. Researchers have used many...  相似文献   
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The kinetics of substrate removal by the liver and the resulting nonlinear changes in unbound fraction along the flow path at varying input drug concentrations were examined by a model simulation study. Specifically, we varied the binding association constant, KA, and the Michaelis-Menten constants (Km and Vmax) to examine the steady state drug removal (expressed as hepatic extraction ratio E) and changes in drug binding for (i) unienzyme systems and (ii) simple, parallel metabolic pathways; zonal metabolic heterogeneity was also added as a variable. At low KA, E declined with increasing input drug concentration, due primarily to saturation of enzymes; only small differences in binding were present across the liver. At high KA, a parabolic profile for E with concentration was observed; changes in unbound fraction between the inlet and the outlet of the liver followed in parallel fashion. Protein binding was the rate-determining step at low input drug concentrations, whereas enzyme saturation was the rate-controlling factor at high input drug concentration. Heterogeneous enzymic distribution modulated changes in unbound fraction within the liver and at the outlet. Despite marked changes in unbound fraction occurring within the liver for different enzymic distributions, the overall transhepatic differences were relatively small. We then investigated the logarithmic average unbound concentration and the length averaged concentration as estimates of substrate concentration in liver in the presence of nonlinear drug binding. Fitting of simulated data, with and without assigned random error (10%), to the Michaelis-Menten equation was performed; fitting was repeated for simulated data obtained with presence of a specific inhibitor of the high-affinity, anteriorly distributed pathway. Results were similar for both concentration terms: accurate estimates were obtained for anterior, high affinity pathways; an overestimation of parameters was observed for the lower affinity posteriorly distributed pathways. Improved estimations were found for posteriorly distributed pathways upon inhibition with specific inhibitors; with added random error, however, the improvement was much decreased. We applied the method for fitting of several sets of metabolic data obtained from rat liver perfusion studies performed with salicylamide (SAM) (i) without and (ii) with the presence of 2,6-dichloro-4-nitrophenol (DCNP), a SAM sulfation inhibitor. The fitted results showed that SAM sulfation was a high-affinity high-capacity pathway; SAM glucuronidation was of lower affinity but comparable capacity as the sulfation pathway, whereas SAM hydroxylation was of lower affinity and lower capacity.  相似文献   
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In this paper two problems on the class of k -trees, a subclass of the class of chordal graphs, are considered: the fast reordering problem and the isomorphism problem. An O(log 2 n) time parallel algorithm for the fast reordering problem is described that uses O(nk(n-k)/\kern -1ptlog n) processors on a CRCW PRAM proving membership in the class NC for fixed k . An O(nk(k+1)!) time sequential algorithm for the isomorphism problem is obtained representing an improvement over the O(n 2 k(k+1)!) algorithm of Sekharan (the second author) [10]. A parallel version of this sequential algorithm is presented that runs in O(log 2 n) time using O((nk((k+1)!+n-k))/log n) processors improving on a parallel algorithm of Sekharan for the isomorphism problem [10]. Both the sequential and parallel algorithms use a concept introduced in this paper called the kernel of a k -tree.  相似文献   
5.
A Confocal Scanning Laser Microscope equipped with a gold image furnace was used to directly observe the precipitation of MnS during solidification of high sulphur steels under isothermal conditions in the temperature region 1440 to 1480°C on the free surface of the steel melt. For the case of Al‐killed steels, below 1480°C MnS particles were found to precipitate with Fe forming simultaneously around them. This MnS containing structure continued to grow rapidly (264 μm/s) as a surface film. The film gradually changed, as the level of S in the melt decreased, into a eutectic structure (with lamella spacing of 2 μm) as predicted by thermodynamics. In Si‐ killed steels there was significantly lower tendency to form MnS both in terms of time until precipitation occurred and growth rate.  相似文献   
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Glucose oxidase (EC 1.1.3.4) was immobilized on different polymeric materials using different immobilization techniques (entrapping by γ‐irradiation, and covalent binding using epichlorohydrin). Studies were carried out to increase the thermal stability of glucose oxidase (GOD) for different applications. The activity and stability of the resulting biopolymers have been compared with those of free GOD. The effect of different polyvinyl alcohol/polyacrylamide (PVA/PAAm) compositions of the copolymer carrier on the enzymatic activity of the immobilized GOD was studied. The maximum enzymatic activity was obtained with the composition ratio of PVA/PAAm of 60:40. The behaviour of the free and immobilized enzyme was analysed as a function of pH. A broadening in the pH profile (5.5–8) was observed for immobilized preparations. The activity and stability of the resulting biopolymers produced by immobilization of GOD onto different carriers have been compared, in both aqueous and organic media, with those of the free GOD. The enzyme's tolerance toward both heat and organic solvent was enhanced by immobilization onto polymers. The addition of different concentrations of organic solvents (10–50%, v/v) to the enzyme at higher temperature (60 °C) was found to stabilize the enzyme molecule. The strongest stabilizing effect on the enzymatic activity was achieved at a concentration of 10%. Copyright © 2005 Society of Chemical Industry  相似文献   
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The purpose of this study was to determine the outcome of patients with metastatic breast cancer treated with high-dose busulfan (Bu), melphalan (Mel) and thiotepa (TT) followed by peripheral blood stem cell (PBSC) infusion. Fifty-one patients with chemotherapy refractory (n = 32) or responsive (n = 19) metastatic breast cancer received Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC collected after chemotherapy and growth factor (n = 43) or growth factor alone (n = 8). The 100 day treatment-related mortality was 8% including one death from cytomegalovirus pneumonia, one from aspiration pneumonia and two from regimen-related toxicity (RRT). Seven of 28 refractory (25%) and 5/7 (71%) responsive patients with evaluable disease achieved a complete response of all measurable disease or all soft tissue disease with at least improvement in bone lesions (PR*). Fifteen of 51 patients (29%) are alive and progression-free a median of 423 days (range 353-934) after treatment, 5/32 (16%) with refractory disease and 10/19 (53%) with responsive disease. The probabilities of progression-free survival (PFS) at 1.5 years for the patients with refractory (n = 32) and responsive (n = 19) disease were 0.24 and 0.53, respectively. These preliminary data suggest that high-dose Bu/Mel/TT has significant activity in patients with advanced breast cancer and may be superior to some previously published regimens.  相似文献   
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How senile plaques and neurofibrillary tangles are linked represents a major gap in our understanding of the pathophysiology of Alzheimer's disease. We characterized a hippocampal neuronal culture system in which tau undergoes maturation in vivo; rat neurons maintained in culture for more than 3 weeks replicated the splicing and phosphorylation changes that tau undergoes upon maturation in situ. Using this model system, we induced an Alzheimer-like neuritic dystrophy following the application of fibrillar beta-amyloid. The dystrophy consisted of focal distortions and swellings within the neurites and an altered phosphorylation of the adult tau isoforms. Fibrillar beta-amyloid induced the concomitant activation of MAP kinase and GSK3 beta. The aberrant activation of several signaling pathways may lead to the abnormal phosphorylation of tau and neuritic degeneration.  相似文献   
10.
In this letter, we report an efficient single-mode Er/sup 3+/ doped fluoride fiber amplifier (EDFFA) in the 850 mn signal band. The Ti-sapphire laser was used to pump the EDFFA at 792 mm with an estimated absorbed pump power of 35 mW. The EDFFA used a 4.2 meter long NA=0.39, /spl lambda//sub c/=850 nm fluoride fiber as the active medium. A peak gain of 25 dB was observed at 852 mm. The gain was measured for a 10 nm region between 847.5 mn and 857.5 nm. The 3 dB gain bandwidth is less than 3 nm. However, the gain exceeded 20 dB over wavelength region of at least 7.5 nm. The gain and the gain bandwidth can be further increased by optimizing the length of the active fiber.  相似文献   
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