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Aminoglycosides are highly potent, broad-spectrum antibiotics that exert their bactericidal therapeutic effect by selectively binding to the decoding aminoacyl site (A-site) of the bacterial 16 S rRNA, thereby interfering with translational fidelity during protein synthesis. The appearance of bacterial strains resistant to these drugs, as well as their relative toxicity, have inspired extensive searches towards the goal of obtaining novel molecular designs with improved antibacterial activity and reduced toxicity. In the last few years, a new, aminoglycoside dependent therapeutic approach for the treatment of certain human genetic diseases has been identified. These treatments rely on the ability of certain aminoglycosides to induce mammalian ribosomes to readthrough premature stop codon mutations. This new and challenging task has introduced fresh research avenues in the field of aminoglycoside research. Recent observations and current challenges in the design of aminoglycosides with improved antibacterial activity and the treatment of human genetic diseases are discussed.  相似文献   
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The growth response of the alga Chlorella kessleri and the euglenoid Euglena gracilis has been studied as a model system to determine the effects of a tin salt (SnCl4·5H2O) and of some organotin (OT) derivatives, namely tetrabutyltin (TeBT), tributyltin (TBT) and tributyltin oxide (TBTO). Abiotic degradation was studied as well. Cells were exposed to a toxicity series (0–50 μg/mL−1) for the four chemicals in seven-day bioassays. Both microorganisms are tolerant of the inorganic salt, but growth inhibition was significant for all OT compounds, and especially large for TBT and TBTO. Although C. kessleri and E. gracilis are known to be tolerant towards metals and organic chemicals, the present results show that both are sensitive to organotin compounds: the inhibition of the growth was greater for C. kessleri. © 1998 John Wiley & Sons, Ltd.  相似文献   
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A combined electronic transport-structure characterization of self-assembled monolayers (MLs) of alkyl-phosphonate (AP) chains on Al-AlOx substrates indicates a strong molecular structural effect on charge transport. On the basis of X-ray reflectivity, XPS, and FTIR data, we conclude that "long" APs (C14 and C16) form much denser MLs than do "short" APs (C8, C10, C12). While current through all junctions showed a tunneling-like exponential length-attenuation, junctions with sparsely packed "short" AP MLs attenuate the current relatively more efficiently than those with densely packed, "long" ones. Furthermore, "long" AP ML junctions showed strong bias variation of the length decay coefficient, β, while for "short" AP ML junctions β is nearly independent of bias. Therefore, even for these simple molecular systems made up of what are considered to be inert molecules, the tunneling distance cannot be varied independently of other electrical properties, as is commonly assumed.  相似文献   
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Potential o-zwitterionic complexes formed between fluorobenzene, p- and o-nitrofluorobenzene with ammonia and amide ion where calculated by CNDU, INDO and MNDO semiempirical methods with a wide geometry optimization. Data for bond lengths, bond angles and charge densities are given. In the case of the complexes with ammonia the reaction coordinate was also calculated by the MNDO procedure. The obtained results show that theoretical calculations can provide useful data on these type of complexes and provide models for systems not amenable to experiment yet.  相似文献   
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Theory of the Krein string is considered in the framework of a continual analog of the theory of unitary operator nodes. On this basis, a generalization of the M. G. Krein-A. A. Nudelman result on the completeness of the string operator is obtained. Bibliography: 28 titles.  相似文献   
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An HPLC method was developed to determine the stability of alprazolam (AL) as a pure drug and in monodrug pharmaceutical tablets. The main degradation product of AL tablets was isolated and fully characterized as triazolaminoquinoleine (TAQ). For a quantitative evaluation of the excipient effects in the pharmaceutical formulations, a 2k fractionated factorial design was applied in the preparation of the different samples. The kinetic of degradation of AL in each formulation was followed by UV spectrophotometry. It was found that excipients like CMC and magnesium stearate favour degradation, while the rate of the reaction is decreased when lactose and starch were used as excipients. A mechanism for the interactions of AL with some excipients is postulated that explains the observed results. Copyright © 2009 John Wiley & Sons, Ltd.  相似文献   
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