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Straub PB Jaffe DE Glass HD Adams MR Brown CN Charpak G Cooper WE Crittenden JA Finley DA Gray R Hemmi Y Hsiung YB Hubbard JR Jonckheere AM Jöstlein H Kaplan DM Lederman LM Luk KB Maki A Mangeot P McCarthy RL Miyake K Plaag RE Rutherfoord JP Sakai Y Santiard JC Sauli F Smith SR Yoshida T Young KK 《Physical review letters》1992,68(4):452-455
95.
G. Evan Boswell David L. Musso James L. Kelley Francis E. Soroko Barret R. Cooper 《Journal of heterocyclic chemistry》1996,33(1):33-39
A series of analogues of 2-phenylmorpholines with alkyl substituents at the C-3 position were synthesized for anti-tetrabenazine (anti-TBZ) testing in mice. The target compounds were prepared by reaction of (2-bromoalkyl) phenyl ketones 21a-h with the appropriate aminoalcohol 20a-b to form morpholinols 22a-h . Hydride reduction of the morpholinols gave aminodiols 23a-h which were cyclized to morpholines 6, 8, 10–12, 14–16, 18 and 19 by acid catalaysis. Compounds 7, 9, 13 and 17 were prepared by reductive formylation. The smaller straight chain substituents of 6, 8, 12 and 15 , and the beta branching of the iso-butyl group of 16 were well tolerated; anti-tetrabenazine ED50′s were comparable to compounds 2–5 . The α-branched, N-methylated, and side chain aryl derivatives were less active. 相似文献
96.
Summary A gas chromatographic methodology with selective detection is presented for the analysis in wines and corks of pentachlorophenol residues, which are suspected to be the most likely precursors of some off-flavours described in several wine samples. After derivatisation, pentachlorophenol acetate residues were monitored by electrolytic conductivity detection and/or mass spectrometric detection in the selective ion mode at m/z 264 and 266. Recoveries varied from 80 to 96% for wine samples fortified with 5 to 100 g l–1 and from 83 to 91% for corks (fortified at 25 to 100 g kg–1). The proposed methodology allowed for a determination limit of g l–1 for wine and 10 g kg–1 for corks. 相似文献
97.
A 28-residue beta-hairpin dimer (WKWK)2 with two Trp and two Lys residues on one face of each beta-sheet was shown to form a complex with single-stranded oligonucleotides at low micromolar concentrations. Each beta-hairpin of the dimer contains a cross-strand Trp-Trp pair in a diagonal orientation which has previously been shown to create a cleft for the intercalation of aromatic guests such as adenine (J. Am. Chem. Soc. 2003, 125, 9580). The beta-hairpin dimer binds 5-residue ssDNA sequences 5'-AAAAA-3', 5'-TTTTT-3', and 5'-CCCCC-3' in water with dissociation constants in the range of 12-30 muM. A weak energetic preference for binding to sequence 5'-AAAAA-3' was observed, which is believed to result from stronger stacking interactions between Trp and the adenine base. The interaction of 5'-AAAAA-3' with the Lys and Trp residues of the peptide was evident by NMR, and a 1:1 association was demonstrated. The recognition of an 11-residue ssDNA sequence occurred with a dissociation constant of 3 muM under near-physiological ionic strength and pH, demonstrating that the beta-hairpin dimer binds ssDNA as strongly as many naturally occurring proteins. The salt dependence of the interaction of the 11-residue oligonucleotide with the peptide dimer indicates that Trp-nucleobase stacking interactions contribute about -4 kcal/mol to recognition, which is much greater than the contribution of nonionic interactions in unstructured peptides containing Trp. Moreover, recognition of the ssDNA demonstrated reduced salt dependence relative to the corresponding duplex, resulting in selectivity for ssDNA under high salt conditions. Peptide (WKWK)2 is a relevant mimic of OB-fold (oligonucleotide/oligosaccharide-binding) proteins which bind ssDNA on the surface of a beta-sheet. 相似文献
98.
A constrained form of the Weber problem is formulated in which no path is permitted to enter a prespecified forbidden region of the plane. Using the calculus of variations the shortest path between two points which does not intersect is determined. If is unconstrained distance, we denote the shortes distance along a feasible path by . The constrained Weber problem is, then: given points and positive weights wj, j = 1,2,…,n, find a point such that is a minimum.An algorithm is formulated for the solution of this problem when is Euclidean distance and is a single circular region. Numerical results are presented. 相似文献
99.
The landscape of synchrotron radiation facilities in Europe is diverse. In addition to the flagship ESRF, several national facilities exist or came into operation recently. In contrast to ESRF, which is financed for use by member countries, access of foreign users to national facilities is not easy. Even if their proposals pass the review process, they can only perform the experiments if funding is allocated to cover not only travel expenses, board and lodging of the experimenters, but also some compensation for the facility's operational costs; this is because national facilities are primarily funded for the home-country's users at that nation's costs. 相似文献
100.
This research effort studies the use of redundant induction coil gauges to reduce state estimation uncertainties for moving Lagrangian points (LPs); e.g. discrete points, moving interfaces, projectiles, etc. The technique embeds a small, high-strength magnet at the LP and simultaneously tracks the magnet continuously with five (5) or more induction coils along a single axis of motion. A calibrated coil gauge model is presented as a function of LP position and velocity. The optimized LP state (position and velocity) estimate based upon redundant LP observations allows direct solution for LP velocity; requiring only one differentiation step to obtain acceleration. A specific experimental implementation (Particulate Materials Meso-scale Diagnostics system) is simulated to evaluate and minimize the expected state estimation errors. Induction coil signals with various levels of noise are simulated based upon a prescribed LP state variation with time. The state optimization algorithm attempts to recover the truth state values. Worst-case position estimation errors of ±0.3 mm and velocity estimation errors of ±0.46 m/s are determined for LPs travelling 0–1,000 m/s at realistic in-lab data noise levels. 相似文献