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排序方式: 共有1417条查询结果,搜索用时 15 毫秒
1.
Chris H. Hill Agnete H. Viuff Samantha J. Spratley Stéphane Salamone Stig H. Christensen Randy J. Read Nigel W. Moriarty Henrik H. Jensen Janet E. Deane 《Chemical science》2015,6(5):3075-3086
Krabbe disease is a devastating neurodegenerative disorder characterized by rapid demyelination of nerve fibers. This disease is caused by defects in the lysosomal enzyme β-galactocerebrosidase (GALC), which hydrolyzes the terminal galactose from glycosphingolipids. These lipids are essential components of eukaryotic cell membranes: substrates of GALC include galactocerebroside, the primary lipid component of myelin, and psychosine, a cytotoxic metabolite. Mutations of GALC that cause misfolding of the protein may be responsive to pharmacological chaperone therapy (PCT), whereby small molecules are used to stabilize these mutant proteins, thus correcting trafficking defects and increasing residual catabolic activity in cells. Here we describe a new approach for the synthesis of galacto-configured azasugars and the characterization of their interaction with GALC using biophysical, biochemical and crystallographic methods. We identify that the global stabilization of GALC conferred by azasugar derivatives, measured by fluorescence-based thermal shift assays, is directly related to their binding affinity, measured by enzyme inhibition. X-ray crystal structures of these molecules bound in the GALC active site reveal which residues participate in stabilizing interactions, show how potency is achieved and illustrate the penalties of aza/iminosugar ring distortion. The structure–activity relationships described here identify the key physical properties required of pharmacological chaperones for Krabbe disease and highlight the potential of azasugars as stabilizing agents for future enzyme replacement therapies. This work lays the foundation for new drug-based treatments of Krabbe disease. 相似文献
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3.
Roger H. Newman 《Cellulose (London, England)》2004,11(1):45-52
Solid-state 13C NMR spectroscopy was used to characterize a bleached softwood kraft pulp in the never-dried state and after cycles of drying and remoistening. Changes in NMR signal strengths indicated that growth of crystalline domains involved cocrystallization rather than accretion of cellulose from noncrystalline domains. A cluster of C-4 signals at 89.4 ppm, assigned to the interiors of crystalline domains, grew at the expense of C-4 signals at 84.0 and 84.9 ppm, assigned to the well-ordered surfaces of crystalline domains. Irreversible changes were not detected until the moisture content dropped below 18%. They were enhanced by a second drying/remoistening cycle, but showed little further change on subsequent cycles. The necessary conditions resembled those reported for hornification, suggesting that cocrystallization might provide a mechanism for hornification. 相似文献
4.
The free groups of exponent eight are shown to differ from thoseof sufficiently large exponent in the nature of their finitesubgroups. 相似文献
5.
It was argued by Schramm and Smirnov that the critical site percolation exploration path on the triangular lattice converges
in distribution to the trace of chordal SLE
6. We provide here a detailed proof, which relies on Smirnov’s theorem that crossing probabilities have a conformally invariant
scaling limit (given by Cardy’s formula). The version of convergence to SLE
6 that we prove suffices for the Smirnov–Werner derivation of certain critical percolation crossing exponents and for our analysis
of the critical percolation full scaling limit as a process of continuum nonsimple loops.
Research of Charles M.Newman was partially supported by the US NSF under grants DMS-01-04278 and DMS-06-06696. 相似文献
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Cardy's formula for some dependent percolation models 总被引:2,自引:0,他引:2
F. Camia C. M. Newman V. Sidoravicius 《Bulletin of the Brazilian Mathematical Society》2002,33(2):147-156
We prove Cardy's formula for rectangular crossing probabilities in dependent site percolation models that arise from a deterministic cellular automaton with a random initial state. The cellular automaton
corresponds to the zero-temperature case of Domany's stochastic Ising ferromagnet on the hexagonal lattice (with alternating
updates of two sublattices) [7]; it may also be realized on the triangular lattice 𝕋 with flips when a site disagrees with
six, five and sometimes four of its six neighbors.
Received: 24 December 2001 相似文献
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J. W. Lee Y. Takase B. A. Newman J. I. Scheinbeim 《Journal of Polymer Science.Polymer Physics》1991,29(3):273-277
Cold-drawn Nylon-11 films, which were prepared by stretching the melt-quenched films to a draw ratio of 2.8: 1 at room temperature, were found to exhibit an electric displacement versus electric field hysteresis loop. The results confirmed that the Nylon-11 film exhibited ferroelectric behavior at or below room temperature. The coercive fields were 65, 98, 125, 160, and 215 MV/m at 20, 0, ?20, ?40, and ?60°C and the remanent polarization at ?20°C (where there was considerably less dc conduction) was 56 mC/m2. Switching of the polarization was almost completed within 20 ms. 相似文献
10.