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91.
J. Conrad J. Cohen-Tanugi L. E. Strigari 《Journal of Experimental and Theoretical Physics》2015,121(6):1104-1135
The launch of the gamma-ray telescope Fermi Large Area Telescope (Fermi-LAT) started a pivotal period in indirect detection of dark matter. By outperforming expectations, for the first time a robust and stringent test of the paradigm of weakly interacting massive particles (WIMPs) is within reach. In this paper, we discuss astrophysical targets for WIMP detection and the challenges they present, review the analysis tools which have been employed to tackle these challenges, and summarize the status of constraints on and the claimed detections in the WIMP parameter space. Methods and results will be discussed in comparison to Imaging Air Cherenkov Telescopes. We also provide an outlook on short term and longer term developments. 相似文献
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93.
Kondakov N. N. Mel´nikova T. M. Chekryzhova T. V. Mel´nikova M. V. Zinin A. I. Torgov V. I. Chizhov A. O. Kononov L. O. 《Russian Chemical Bulletin》2015,64(5):1142-1148
Russian Chemical Bulletin - Terminal disaccharide fragment of phenolic glycolipid from Mycobacterium leprae (PGL-I) was synthesized as a glycoside with 4-(2-aminoethoxy)phenyl aglycon. The obtained... 相似文献
94.
Claudia Poloni Marc C. A. Stuart Pieter van der Meulen Wiktor Szymanski Ben L. Feringa 《Chemical science》2015,6(12):7311-7318
The external photocontrol over peptide folding, by the incorporation of molecular photoswitches into their structure, provides a powerful tool to study biological processes. However, it is limited so far to switches that exhibit only a rather limited geometrical change upon photoisomerization and that show thermal instability of the photoisomer. Here we describe the use of an overcrowded alkene photoswitch to control a model β-hairpin peptide. This photoresponsive unit undergoes a large conformational change and has two thermally stable isomers which has major influence on the secondary structure and the aggregation of the peptide, permitting the phototriggered formation of amyloid-like fibrils. 相似文献
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Kinetics and Catalysis - Boron and barium were employed as dopants for the VMgO system. The catalysts were characterized by ICP-OES, BET, IR, powder XRD, EDX, TPR-H2, TPD-NH3, XPS, and 51V MAS NMR.... 相似文献
98.
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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Natalia L. Calvo Sebastian O. SimonettiRubén M. Maggio Teodoro S. Kaufman 《Analytica chimica acta》2015
Exposure of cimetidine (CIM) to dry heat (160–180 °C) afforded, upon cooling, a glassy solid containing new and hitherto unknown products. The kinetics of this process was studied by a second order chemometrics-assisted multi-spectroscopic approach. Proton and carbon-13 nuclear magnetic resonance (NMR), as well as ultraviolet and infrared spectroscopic data were jointly used, whereas multivariate curve resolution with alternating least squares (MCR-ALS) was employed as the chemometrics method to extract process information. It was established that drug degradation follows a first order kinetics. 相似文献