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101.
Laras Y Quéléver G Garino C Pietrancosta N Sheha M Bihel F Wolfe MS Kraus JL 《Organic & biomolecular chemistry》2005,3(4):612-618
Inhibition of gamma-secretase, one of the enzymes responsible for the cleavage of the amyloid precursor protein (APP) to produce pathogenic A beta peptides, is an attractive approach for the treatment of Alzheimer's disease. We have designed a new gamma-secretase thiazolamide inhibitor bearing a dihydronicotinoyl moiety as Redox Delivery System which allows specific delivery of the drug to the brain. Through, on the one hand, A beta peptide production measurements by specific in vitro assays (gamma-secretase Cell Free assay and Cell Based assay on HEK 293 APP transfected cells) and, on the other hand, pharmacokinetic studies on animal models, the new inhibitor shows a good pharmacokinetic profile as well as a potent gamma-secretase inhibitory activity in vitro. From the obtained results, it is expected that drug will be mainly delivered to the CNS with low diffusion in the peripheral tissues. Consequently the side effects of this gamma-secretase inhibitor on the immune cells could be reduced. 相似文献
102.
Phase-sensitive optical low-coherence reflectometry technique applied to the characterization of photonic crystal fiber properties 总被引:3,自引:0,他引:3
Palavicini C Jaouën Y Debarge G Kerrinckx E Quiquempois Y Douay M Lepers C Obaton AF Melin G 《Optics letters》2005,30(4):361-363
Localized measurements of group-velocity dispersion and birefringence of photonic crystal fibers are achieved with a phase-sensitive optical low-coherence reflectometry technique. This technique is efficient for fiber samples no longer than 1 m. Theoretical simulations are in good agreement with experimental results. As a result, the stress-induced birefringence proves to be at most 1 order of magnitude below the geometrical-shape birefringence. 相似文献
103.
We carried out a numerical study of the second mode transition in finite-sized, microstructured optical fibers (MOFs) for several values of the matrix refractive index. We determined a unique critical geometrical parameter for the second mode cutoff that is valid for all the matrix refractive indices studied. Finite size effects and extrapolated results for infinite structures are described. Using scaling laws, we provide a generalized phase diagram for solid-core MOFs that is valid for all refractive indices, including those of the promising chalcogenide MOFs. 相似文献
104.
The sound field inside a model human ear canal has been computed, to show both longitudinal variations along the canal length and transverse variations through cross-sectional slices. Two methods of computation were used. A modified horn equation approach parametrizes the sound field with a single coordinate, the position along a curved center axis-this approach can accommodate the curvature and varying cross-sectional area of the ear canal but cannot compute transverse variations of the sound field. A boundary element method (BEM) was also implemented to compute the full three-dimensional sound field. Over 2000 triangular mesh elements were used to represent the ear canal geometry. For a plane piston source at the entrance plane, the pressure along the curved center axis predicted by the two methods is in good agreement, for frequencies up to 15 kHz, for four different ear canals. The BEM approach, though, reveals spatial variations of sound pressure within each canal cross section. These variations are small below 4 kHz, but increase with frequency, reaching 1.5 dB at 8 kHz and 4.5 dB at 15 kHz. For source configurations that are more realistic than a simple piston, large transverse variations in sound pressure are anticipated in the vicinity of the source. 相似文献
105.
We study the quantum transport through networks of diffusive wires connected to reservoirs in the Landauer-Büttiker formalism. The elements of the conductance matrix are computed by the diagrammatic method. We recover the combination of classical resistances and obtain the weak localization corrections. For arbitrary networks, we show how the Cooperon must be properly weighted over the different wires. Its nonlocality is clearly analyzed. We predict a new geometrical effect that may change the sign of the weak localization correction in multiterminal geometries. 相似文献
106.
Huge fluctuations in weight measurements at the bottom of a two-dimensional vertical sheet of grains
Weight measurements at the bottom of a quasi-2D vertical sheet of static cohesionless grains are carried out. The grains are held between two coaxial cylinders. This peculiar setup allows us to set either periodic or fixed lateral boundary conditions. Huge relative fluctuations in weight measurements appear in case of fixed lateral walls. This may be related to some indetermination in the mobilization state of friction forces on lateral walls. This argument would hold for any piling, but would lead to huge fluctuations in 2D systems only, because of averaging effects in 3D. 相似文献
107.
The increased sensitivity of hearing aids to feedback as a telephone handset is brought near has been studied experimentally and numerically. For the measurements, three different hearing aids were modified so that the open-loop transfer function could be measured. They were mounted in the pinna of a mannikin and the change in open-loop transfer function determined as a function of handset proximity. Increases of over 20 dB were observed, most of this change occurring within the first 10 mm of separation between pinna and handset. Numerical calculations performed using a boundary element technique were in good agreement with the measurements. 相似文献
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Poschalko A Rohr T Gruber H Bianco A Guichard G Briand JP Weber V Falkenhagen D 《Journal of the American Chemical Society》2003,125(44):13415-13426
A novel SUcrose-Based Polymer support (SUBPOL) with tailored morphology suitable for the use in solid-phase peptide synthesis (SPPS) is described, and its application as a hydrophilic affinity matrix for the specific removal of fibrinogen from human plasma is demonstrated. After suspension polymerization of partly methacrylated 2,1':4,6-di-O-isopropylidene sucrose and subsequent removal of the protecting groups, hydrophilic spherical polymer beads were obtained. The morphology of the resulting resin was controlled by variation of the porogen as well as the average degree of substitution with respect to the methacryloyl groups of the monomer mixture. After introduction of amino groups for a permanent attachment of immobilized peptide ligands, prevention of unintended esterification during SPPS was achieved by silylation of remaining hydroxy groups. Alternatively, a Rink amide linker was introduced prior to SPPS to allow cleavage and subsequent analysis of the peptide assembled on the SUBPOL resins. Two hexapeptides of sequence kwiivw and hffflw, consisting of d-amino acids, as well as a 19-mer peptide corresponding to the sequence GSGVRGDFGSLAPRVARQL of the VP1 protein from the foot-and-mouse disease virus (FMDV) were successfully prepared both manually or in a semi-automated process on SUBPOL resins according to the Fmoc/tBu strategy. Yields and purities were comparable to peptides prepared on commercially available polystyrene resins. A specific affinity adsorbent containing the fibrinogen-binding pentapeptide GPRPK was prepared by SPPS on SUBPOL resins of different morphology, and the strong impact of the affinity matrix on adsorption performance was demonstrated. 相似文献