Chiral molecules, especially enantiomers and diastereomers of purity > 99 %, present a significant market share within the chemical, pharmaceutical, and flavor industries. Antisolvent precipitations, both batch and semicontinuous operations to serve the current trends in flow chemistry were demonstrated to be environmentally benign and efficient tools in achieving high optical purities. Although salts are known to be insoluble in supercritical CO2, instabilities of the nascent salts were detected and applied for increasing efficiency. Diastereomeric excess values of the crystalline products exceeded 99 % in maximum of three consecutive steps both by repeated resolution with half molar equivalent of the amine to the acid and by direct recrystallization of the salts. 相似文献
The nucleotide analog sofosbuvir, licensed for the treatment of hepatitis C, recently revealed activity against the Zika virus (ZIKV) in vitro and in animal models. However, the ZIKV genetic barrier to sofosbuvir has not yet been characterized. In this study, in vitro selection experiments were performed in infected human hepatoma cell lines. Increasing drug pressure significantly delayed viral breakthrough (p = 0.029). A double mutant in the NS5 gene (V360L/V607I) emerged in 3 independent experiments at 40–80 µM sofosbuvir resulting in a 3.9 ± 0.9-fold half- maximal inhibitory concentration (IC50) shift with respect to the wild type (WT) virus. A triple mutant (C269Y/V360L/V607I), detected in one experiment at 80 µM, conferred a 6.8-fold IC50 shift with respect to the WT. Molecular dynamics simulations confirmed that the double mutant V360L/V607I impacts the binding mode of sofosbuvir, supporting its role in sofosbuvir resistance. Due to the distance from the catalytic site and to the lack of reliable structural data, the contribution of C269Y was not investigated in silico. By a combination of sequence analysis, phenotypic susceptibility testing, and molecular modeling, we characterized a double ZIKV NS5 mutant with decreased sofosbuvir susceptibility. These data add important information to the profile of sofosbuvir as a possible lead for anti-ZIKV drug development. 相似文献
The Journal of Supercomputing - Deadlock-free dynamic network reconfiguration process is usually studied from the routing algorithm restrictions and resource reservation perspective. The dynamic... 相似文献
This paper presents a PVS development of relevant results of the theory of rings. The PVS theory includes complete proofs of the three classical isomorphism theorems for rings, and characterizations of principal, prime and maximal ideals. Algebraic concepts and properties are specified and formalized as generally as possible allowing in this manner their application to other algebraic structures. The development provides the required elements to formalize important algebraic theorems. In particular, the paper presents the formalization of the general algebraic-theoretical version of the Chinese remainder theorem (CRT) for the theory of rings, as given in abstract algebra textbooks, proved as a consequence of the first isomorphism theorem. Also, the PVS theory includes a formalization of the number-theoretical version of CRT for the structure of integers, which is the version of CRT found in formalizations. CRT for integers is obtained as a consequence of the general version of CRT for the theory of rings.
Lipases are hydrolytic enzymes that break the ester bonds of triglycerides, generating free fatty acids and glycerol. Extracellular lipase activity has been reported for the nonconventional yeast Kluyveromyces marxianus, grown in olive oil as a substrate, and the presence of at least eight putative lipases has been detected in its genome. However, to date, there is no experimental evidence on the physiological role of the putative lipases nor their structural and catalytic properties. In this study, a bioinformatic analysis of the genes of the putative lipases from K. marxianus L-2029 was performed, particularly identifying and characterizing the extracellular expected enzymes, due to their biotechnological relevance. The amino acid sequence of 10 putative lipases, obtained by in silico translation, ranged between 389 and 773 amino acids. Two of the analysed putative proteins showed a signal peptide, 25 and 33 amino acids long for KmYJR107Wp and KmLIP3p, and a molecular weight of 44.53 and 58.23 kDa, respectively. The amino acid alignment of KmLIP3p and KmYJR107Wp with the crystallized lipases from a patatin and the YlLip2 lipase from Yarrowia lipolytica, respectively, revealed the presence of the hydrolase characteristic motifs. From the 3D models of putative extracellular K. marxianus L-2029 lipases, the conserved pentapeptide of each was determined, being GTSMG for KmLIP3p and GHSLG for KmYJR107Wp; besides, the genes of these two enzymes (LIP3 and YJR107W) are apparently regulated by oleate response elements. The phylogenetic analysis of all K. marxianus lipases revealed evolutionary affinities with lipases from abH15.03, abH23.01, and abH23.02 families. 相似文献
This study aims to evaluate the tribological behaviour of 3Y-TZP/Ta (20 vol%) ceramic-metal composites and 3Y-TZP monolithic ceramic prepared by spark plasma sintering (SPS) against ultrahigh molecular weight polyethylene (UHMWPE). According to the results of pin (UHMWPE)-on-flat wear test under dry conditions, the UHMWPE – 3Y-TZP/Ta system exhibited lower volume loss and friction coefficient than the UHMWPE – monolithic ceramic combination due to the presence of an autolubricating layer that provides sufficient lubrication for reducing the friction. Owing to the lubrication of the liquid media, under wet conditions obtained using simulated body fluid (SBF), similar behaviour is observed in both cases. Additionally, the ceramic and biocomposite materials were subjected to a low temperature degradation (LTD) process (often referred to as “ageing”) to evaluate the changes in the tribological behaviour after this treatment. In this particular case, the wear properties of the UHMWPE-biocomposite system were found to be less influenced by ageing in contrast to the case of the UHMWPE-zirconia monolithic material. In addition to their exceptional mechanical performance, 3Y-TZP/Ta composites also showed high resistance to low temperature degradation and good tribological properties, making them promising candidates for biomedical applications, especially for orthopaedic implants. 相似文献