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991.
There has been a discrepancy between promising results of experimental chemotherapy in animal melanoma models and clinical response rates. This inconsistency seems to reflect weak points of the assays used so far to monitor the response of melanoma cells to chemotherapeutic agents. Therefore a less usual approach was chosen in the present study: Tumor cells were cultured in peritoneal cavity (B16 melanoma in inbred C57BL/6J mice and Cloudman S91 melanoma in inbred DBA2 mice) to maintain normal in vivo conditions; the animals were receiving the tested agents in i.p. injections and the prolongation of their life span was considered as the principle parameter of therapeutic efficiency of the compounds tested. Previously described therapeutic potency both of vitamins (C, alpha-tocopherol acid succinate) and some phenols (hydroquinone, 4-hydroxyanisole) was confirmed. Benzoate, spin trap N-butyl-alpha-phenyl-nitrone and ammonium chloride as a lysosomotropic agent failed to increase the survival of melanoma-bearing mice. Free radical scavenger methimazole exerted a therapeutic effect in mice with pigmented B16 melanoma. Only classic cytostatic agents--cisplatin and cyclophosphamide--proved its therapeutic effect in both melanoma models studied. These results are in accord with the known resistance of human melanoma to conventional chemotherapy. Measurement of serum activity of gamma-glutamyltransferase was shown to be useful for monitoring therapeutic effect.  相似文献   
992.
This paper discusses systematic methods for diagnosis of complex engineering systems combining qualitative and quantitative analysis of analytic constraint equation system models to generate more precise and accurate candidates. Candidates generated from a qualitative steady-state partial explanation model are refined with available ordinal information on the magnitude of component parameter deviations. In addition, an incremental algorithm is implemented to efficiently process sequences of measurements. Empirical analysis demonstrates that accuracy and resolution of minimal candidate generation are improved by including ordinal information. This avoids the practical problems encountered when reasoning with pure quantitative information  相似文献   
993.
Intracellular ionic strength regulates myriad cellular processes that are fundamental to cellular survival and proliferation, including protein activity, aggregation, phase separation, and cell volume. It could be altered by changes in the activity of cellular signaling pathways, such as those that impact the activity of membrane-localized ion channels or by alterations in the microenvironmental osmolarity. Therefore, there is a demand for the development of sensitive tools for real-time monitoring of intracellular ionic strength. Here, we developed a bioluminescence-based intracellular ionic strength sensing strategy using the Nano Luciferase (NanoLuc) protein that has gained tremendous utility due to its high, long-lived bioluminescence output and thermal stability. Biochemical experiments using a recombinantly purified protein showed that NanoLuc bioluminescence is dependent on the ionic strength of the reaction buffer for a wide range of ionic strength conditions. Importantly, the decrease in the NanoLuc activity observed at higher ionic strengths could be reversed by decreasing the ionic strength of the reaction, thus making it suitable for sensing intracellular ionic strength alterations. Finally, we used an mNeonGreen–NanoLuc fusion protein to successfully monitor ionic strength alterations in a ratiometric manner through independent fluorescence and bioluminescence measurements in cell lysates and live cells. We envisage that the biosensing strategy developed here for detecting alterations in intracellular ionic strength will be applicable in a wide range of experiments, including high throughput cellular signaling, ion channel functional genomics, and drug discovery.  相似文献   
994.
995.
This study focuses upon the evolution of microstructures during solidification processing of several intermetallic alloys around the Ll2 phase in the Al-rich corner of the Al-Ti-Ni ternary system. The alloys were produced by double induction melting and subsequent homogenization followed by furnace cooling. The microstructure was characterized by means of optical and scanning electron microscopy with energy-dispersive spectroscopy (EDS) analysis and X-ray diffraction. The microstructural evolution in homogenized alloys was dependent on both nickel and titanium content. Very fine precipitates of Al2Ti were observed within the Ll2 phase in alloys containing 62 to 65 at. pct Al and at least 25 at. pct Ti. The Al2Ti precipitates are stable at least up to 1000 °C and undergo complete dissolution at 1200 °C. In alloys containing around 66 at. pct Al and 25 to 31 at. pct Ti, phases such as Al3Ti, Al5Ti2, and Al11Ti5 were observed. A modified room temperature isotherm in the Al-Ti-Ni ternary system is proposed, taking into account the existence of Al2Ti, Al11Ti5, Al5Ti2, and Al3Ti in equilibrium with the Ll2 phase. It seems that at room temperature, the Ll2 phase field for homogenized alloys is extremely small. It will be practically impossible to obtain a single-phase microstructure at room temperature in the Al-Ti-Ni ternary alloys after homogenization at 1000 °C followed by furnace cooling. S. BISWAS, formerly Graduate Student, Department of Mechanical Engineering, University of Waterloo  相似文献   
996.
In this paper, a combined experimental and numerical investigation of free hydroforming of aluminium alloy tubes is conducted. The tubes are subjected to different loading histories involving axial compression and internal pressure. The circumferential and axial strains experienced by the tubes are continuously recorded along with the pressure and axial load. The numerical simulations are carried out using both 2D axisymmetric and 3D finite-element formulations by applying the experimentally recorded axial load and internal pressure. In the latter, a geometric imperfection is introduced in the form of wall thickness reduction at the tube mid-length in order to trigger necking which happens after significant bulging and beyond the stage of peak pressure. The strain histories and peak pressures obtained from the simulations agree well with those determined from the experiments. Further, the forming limit curve predicted by the simulations as well as from a M–K analysis incorporating the computed strain paths corroborate well with the experimental data. The role of nonproportional straining on the mechanics of failure of the tubes due to bulging and necking is studied in detail.  相似文献   
997.
We have assessed the effect of two induction agents on tracheal intubating conditions after rocuronium 0.6 mg.kg-1 in unpremedicated patients undergoing simulated rapid sequence induction. Following pre-oxygenation, anaesthesia was induced with propofol up to 2.5 mg.kg-1 (n = 35) or etomidate 0.3 mg.kg-1 (n = 36), and further increments as required. After loss of verbal contact, cricoid pressure was applied and rocuronium was injected. Laryngoscopy was performed at 45 s and intubation attempted at 60 s after rocuronium had been given. Ninety-four per cent of patients in the propofol group had clinically acceptable (good or excellent) intubating conditions compared to only 75% in the etomidate group (p = 0.025). Owing to coughing, one patient in the etomidate group could not be intubated on the first attempt. A greater pressor response also followed intubation after induction with etomidate. We conclude that etomidate and rocuronium alone cannot be recommended for intubation at 60 s under rapid sequence induction conditions.  相似文献   
998.
Water‐dispersible conducting nanocomposites were prepared by precipitating polyaniline (PANI)/polypyrrole (PPY) in an aqueous suspension of polyacrylonitrile–SiO2 (PAN–SiO2) via K2CrO4–NaAsO2 redox polymerization. Incorporation of PANI and PPY in the composites was confirmed by the FTIR spectrum. Scanning electron microscopic analyses for the PANI–(PAN–SiO2) and PPY–(PAN–SiO2) composites indicated formation of lumpy aggregates with irregular sizes. TEM analyses revealed formation of spherical particles with size ranging between 80 and 150 nm for PANI–(PAN–SiO2) nanocomposite and 75–150 nm for PPY‐(PAN‐SiO2) nanocomposites, respectively. Thermal stabilities of the PANI–(PAN–SiO2) and PPY–(PAN–SiO2) nanocomposites were higher than those of the individual base polymers. Conductivity values of PANI–(PAN–SiO2) nanocomposite (10?3 S cm?1) and PPY–(PAN–SiO2) nanocomposite (10?4 S cm?1) were remarkably improved relative to that for PAN homopolymer (>10?11 S cm?1). Both of these composites produced a permanently stable aqueous suspension when the polymerization was conducted in presence of nanodimensional SiO2 as a particulate dispersant. Copyright © 2004 Society of Chemical Industry  相似文献   
999.
Aggressive responding was compared between 29 subjects with a history of substance dependence and 24 subjects with no drug use history, using the Point Subtraction Aggression Paradigm. The hypothesis was that subjects from the substance dependence history group would emit more aggressive responses than subjects with no drug use history. The substance dependence history group emitted more aggressive responses per session than the non drug using group (F(1,49) = 14.867, P = 0.032). These results are consistent with previous studies that have reported an association between aggression and drug abuse or dependence.  相似文献   
1000.
The spatiotemporal organization of the mechanically evoked perioral sensorimotor response was sampled from five normal females using a custom-designed linear motor operating under force feedback. Electromyographic activity was sampled from the superior and inferior segments of the orbicularis oris muscle during the production of a visually guided ramp-and-hold lip-rounding task. Brief mechanical inputs of approximately 0.45 N delivered to the left upper lip during the ramp-and-hold task produced a composite myogenic response characterized by phases of excitation and suppression. Modulation of the primary excitatory component (R1) of the mechanically evoked perioral response was found to be highly dependent upon the rate of force recruitment (1 N/s vs. 4 N/s) and the phase of force recruitment (20% vs. 50% vs. 80% of 1 N end-point force). Modulation of later occurring inhibitory (S1) and excitatory (R2) potentials were also found to be dependent upon differences in the rate and phase of force recruitment. The organization of the perioral sensorimotor response is considered in relation to speech motor control and the dynamic organization of neuronal groups subserving perioral sensorimotor activity.  相似文献   
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