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1.
Back Cover: Reactions of Group 4 Metallocenes with Monosubstituted Acetonitriles: Keteniminate Formation versus CC Coupling (Chem. Eur. J. 8/2015) 下载免费PDF全文
2.
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
3.
Wolfram Bremser Roland Becker Heinrich Kipphardt Petra Lehnik-Habrink Ulrich Panne Antje Töpfer 《Accreditation and quality assurance》2006,11(10):489-495
ISO Guide 35 deals with RM stability issues and scrutinizes the evaluation of stability testing results under the assumption that either there is no trend at all (a rather rare situation), or any observed deterministic change is insignificant and thus can be neglected. However, market demands for reliable reference materials are obviously not limited to stable or at least seemingly stable materials. In many analytical applications, analytes and measurands under consideration are known, or at least suspected, to be unstable on time scales that may vary widely from measurand to measurand. The Federal Institute for Materials Research and Testing (BAM) has developed (and successfully uses) an integrated approach in its certification practice. The approach is based on an initial stability study and subsequent post-certification monitoring. Data evaluation is model-based and takes advantage of all information collected in the stability testing scheme(s). It thus allows one to deal with any kind of instability observed, to assess limiting time intervals at any stress condition in the range tested, to estimate a final expiry date for materials with detected instabilities or the maximum admissible re-testing interval for seemingly stable materials, and to assess maximum admissible stress loads during delivery of the material to the customer. The article describes (and exemplifies) typical study layout, the model selection, and the integrated data assessment. 相似文献
4.
T. Engel M. Würtz S. Borneis St. Becker I. Klaft A. Kohl T. Kühl F. Laeri D. Marx K. Meier R. Neumann F. Schmitt P. Seelig L. Völker 《Hyperfine Interactions》1997,108(1-3):251-258
Laser spectroscopy at storage rings often suffers from a limited resolution due to Doppler-broadened resonances. Broadening
is caused by the velocity spread of the ions stored in the beam. In the following, the present status of our work on laser
systems specialized on the specific needs of laser spectroscopy at storage rings is reported.
Two pulsed laser systems were developed. One is a dye laser whose spectral bandwidth can be switched by inserting different
Littrow-prisms into the resonator. An increase in bandwidth up to a factor of 45 was achieved. This laser was used for fast
qualitative scans and high resolution measurements. The other laser system is a Nd : YAG laser pumped optical parametric oscillator.
It is a tunable laser system covering the spectral range from 410 to 4000 nm. Furthermore, a continuous wave laser with a
frequency shifted feedback cavity is described. It shows broadband emission with an adjustable bandwidth of up to 4.5 GHz.
This laser can be advantageous for laser cooling of ion beams.
This revised version was published online in August 2006 with corrections to the Cover Date. 相似文献
5.
The difference in reactivity of the two modifications of InCl in solid state reactions with SnCl2 is discussed. It is explained on the basis of semi‐empirical and ab initio calculations giving the density of states diagrams of InCl and the energies of possible disproportionation reactions. Their general features are discussed on the basis of a simple bonding picture for open‐packed structures involving inert pair elements. A detailed analysis of the DOS distribution allows to pinpoint the observed redox instability to a specific structural feature of α‐InCl. 相似文献
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7.
Ronald I. Becker Isabella Lari Andrea Scozzari Giovanni Storchi 《Annals of Operations Research》2007,150(1):65-78
In this paper we consider the location of a path shaped facility on a grid graph. In the literature this problem was extensively
studied on particular classes of graphs as trees or series-parallel graphs. We consider here the problem of finding a path
which minimizes the sum of the (shortest) distances from it to the other vertices of the grid, where the path is also subject
to an additional constraint that takes the form either of the length of the path or of the cardinality. We study the complexity
of these problems and we find two polynomial time algorithms for two special cases, with time complexity of O(n) and O(nℓ) respectively, where n is the number of vertices of the grid and ℓ is the cardinality of the path to be located.
The literature about locating dimensional facilities distinguishes between the location of extensive facilities in continuous
spaces and network facility location. We will show that the problems presented here have a close connection with continuous
dimensional facility problems, so that the procedures provided can also be useful for solving some open problems of dimensional
facilities location in the continuous case. 相似文献
8.
The Nd:YAG laser-induced breakdown of 20 μm glass microspheres was investigated using time-resolved optical shadow and Schlieren images. Time-resolved imaging showed the location of the initial breakdown and the shockwave motion over its first 400 μm of expansion. Measured shockwave velocities were in the range of 1–10 km/s and showed a linear dependency on laser fluence within 30 ns. 相似文献
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