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71.
Hyperphosphorylated tau is the major component of paired helical filaments in neurofibrillary lesions associated with Alzheimer's disease. Hyperphosphorylation reduces the affinity of tau for microtubules and is thought to be a critical event in the pathogenesis of this disease. Recently, glycogen-synthase kinase-3 has been shown to phosphorylate tau in vitro and in non-neuronal cells transfected with tau. The activity of glycogen-synthase kinase-3 can be down-regulated in response to insulin or insulin-like growth factor-1 through the activation of the phosphatidylinositol 3-kinase pathway. We therefore hypothesize that insulin or insulin-like growth factor-1 may affect tau phosphorylation through the inhibition of glycogen-synthase kinase-3 in neurons. Using cultured human neuronal NT2N cells, we demonstrate that glycogen-synthase kinase-3 phosphorylates tau and reduces its affinity for microtubules and that insulin and insulin-like growth factor-1 stimulation reduces tau phosphorylation and promotes tau binding to microtubules. We further demonstrate that these effects of insulin and insulin-like growth factor-1 are mediated through the inhibition of glycogen-synthase kinase-3 via the phosphatidylinositol 3-kinase/protein kinase B signaling pathway. 相似文献
72.
This paper studies a particular single-stage power-factor-correction (PFC) switching regulator employing a discontinuous-conduction-mode (DCM) boost-input cell and a continuous-current-mode (CCM) forward output cell. Although this single-stage PFC regulator can provide a reasonably high power factor when its PFC stage is operating in discontinuous mode, substantial reduction in line-current harmonics is possible by applying a suitable frequency-modulation scheme. This paper derives a frequency-modulation scheme and proposes a practical implementation using a simple translinear analog circuit. A quantitative analysis on the total harmonic distortion (THD) of the line current when the circuit is subject to a limited range of frequency variations is presented along with some considerations for practical design. Experimental data obtained from a prototype confirms the effectiveness of the proposed frequency-modulation scheme. The proposed analog translinear circuit allows custom integrated circuit implementation, making it a viable low-cost solution to the elimination of line-current harmonics in switching regulators 相似文献
73.
74.
Chengkuo Lee Itoh T. Suga T. 《IEEE transactions on ultrasonics, ferroelectrics, and frequency control》1996,43(4):553-559
A micromachined lead zirconate titanate (PZT) force sensor for scanning force microscope (SFM) is conceptualized by its piezoelectricity. The fabrication procedure is interpreted, and mechanical characteristics of the micromachined PZT force sensors with various lengths are studied in this paper. A compact SFM is constructed by using the piezoelectric PZT sensor. A very clear image is taken by this SFM. The current study of the micromachined PZT force sensor can be considered as a breakthrough of design of SFM as well as a good example of integrated piezoelectric microdevices 相似文献
75.
The AA7075 alloys reinforced with SiC and without SiC particles were fabricated by a pressureless infiltration method, and
then, their tensile properties and microstructures were analyzed. The spontaneous infiltration of molten metal at 800 °C for
1 hour under a nitrogen atmosphere made it possible to fabricate 7075 Al matrix composite reinforced with SiC, as well as
a control 7075 Al without SiC. A significant strengthening even in the control alloy occurred due to the formation of in-situ AlN particle even without an addition of SiC particles. Composite reinforced with SiC particles exhibited higher strength
values than the control alloy in all aging conditions (underaged (UA), peak-aged (PA), and overaged (OA)), as well as a solution
treated condition. Spontaneous infiltration was further prompted owing to the combined effect of both Mg and Zn. This may
lead to an enhancement of wetting between the molten alloy and the reinforcement. Consequently, strength improvement in a
composite may be attributed to good bond strength via enhancement of wetting. The grain size of the control alloy is greatly decreased to about 2.5 μm compared to 10 μm for the
commercial alloy. In addition, the grain size in the composite is further decreased to about 2 μm. These grain refinements
contributed to strengthening of the control alloy and the composite. 相似文献
76.
77.
BH Shieh MY Zhu JK Lee IM Kelly F Bahiraei 《Canadian Metallurgical Quarterly》1997,94(23):12682-12687
Visual transduction in Drosophila is a G protein-coupled phospholipase C-mediated process that leads to depolarization via activation of the transient receptor potential (TRP) calcium channel. Inactivation-no-afterpotential D (INAD) is an adaptor protein containing PDZ domains known to interact with TRP. Immunoprecipitation studies indicate that INAD also binds to eye-specific protein kinase C and the phospholipase C, no-receptor-potential A (NORPA). By overlay assay and site-directed mutagenesis we have defined the essential elements of the NORPA-INAD association and identified three critical residues in the C-terminal tail of NORPA that are required for the interaction. These residues, Phe-Cys-Ala, constitute a novel binding motif distinct from the sequences recognized by the PDZ domain in INAD. To evaluate the functional significance of the INAD-NORPA association in vivo, we generated transgenic flies expressing a modified NORPA, NORPAC1094S, that lacks the INAD interaction. The transgenic animals display a unique electroretinogram phenotype characterized by slow activation and prolonged deactivation. Double mutant analysis suggests a possible inaccessibility of eye-specific protein kinase C to NORPAC1094S, undermining the observed defective deactivation, and that delayed activation may similarly result from NORPAC1094S being unable to localize in close proximity to the TRP channel. We conclude that INAD acts as a scaffold protein that facilitates NORPA-TRP interactions required for gating of the TRP channel in photoreceptor cells. 相似文献
78.
Synthesis of poly(gamma-glutamate) metabolites of natural folates and antifolates is a critical process. Folypolyglutamates are essential for cell proliferation. Polyglutamates of glutamate (Glu)-containing antifolates are often critical for their cytotoxic action and are relevant to antifolate resistance. However, the role of polyglutamate synthesis in selectivity is less clear. We have undertaken a research program to further define the significance of polyglutamate metabolism and to devise ways to exploit this metabolism to achieve greater therapeutic selectivity in cancer chemotherapy. This article briefly reviews several approaches tested thus far. Inhibition of folypolyglutamate synthesis should lead to cell death. Current ornithine (Orn)-containing folate-based inhibitors of the enzyme responsible for their synthesis, folypolyglutamate synthetase (FPGS), are poorly transported, apparently because of interference by the protonated delta-amine. Replacement of Orn with 4, 4-difluoroOrn, the delta-amine of which has a much lower pKa and is thus less protonated at physiological pH, was explored. Since it is unclear how polyglutamylation contributes to selectivity, we explored generic means either to eliminate or to enhance polyglutamylation. The data indicate that substitution for Glu in an antifolate by some Glu analogs in which the gamma-COOH is either altered or replaced (e.g., gamma-tetrazole-Glu) leads to loss of both FPGS substrate activity and binding; antifolate target specificity is unchanged, while uptake is actually enhanced. Substitution of 3,3-difluoroGlu for Glu leads to enhanced polyglutamylation (although probably only to the diglutamate), retention of target specificity, and at least equal uptake. Comparative studies of the same antifolate containing different replacements for Glu, such as gamma-tetrazole-Glu (no polyglutamylation) or 3,3-difluoroGlu (enhanced polyglutamylation), will be useful in exploring the role and significance of polyglutamylation. 相似文献
79.
80.
Kwang Soo Lee In Soo Park & Dong Sun Lee 《International Journal of Food Science & Technology》1996,31(1):7-13
The aim of this study was to design a modified atmosphere package for a mixed vegetable salad consisting of 75 g of cut carrot, 55 g of cut cucumber, 20 g of sliced garlic and 50 g of whole green pepper. Respiration data of all the components were combined with film permeability data to predict package atmospheres and design optimal packages for experimental testing for improved shelf-life of the produce. The optimal package avoided minimum O2 and maximum CO2 tolerance limits, and chilling injury temperatures for any component. A pouch form package made of 27 mm low density polyethylene developed a modified atmosphere of 2.0–2.1% O2 and 5.5–5.7% CO2 , which was beneficial for all components and provided better quality retention than other test packages. 相似文献