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1.
Capt. Courtney Kiggins Austin Skinner Prof. Marino J. E. Resendiz 《Chembiochem : a European journal of chemical biology》2020,21(9):1347-1355
Aptamers are attractive constructs due to their high affinity/selectivity towards a target. Here 7,8-dihydro-8-oxoguanosine (8-oxoG) has been used, due in part to its unique H-bonding capabilities (Watson–Crick or Hoogsteen), to expand the “RNA alphabet”. Its impact on the theophylline RNA aptamer was explored by modifying its binding pocket at positions G11, G25, or G26. Structural probing, with RNases A and T1, showed that modification at G11 leads to a drastic structural change, whereas the G25-/G26-modified analogues exhibited cleavage patterns similar to that of the canonical construct. The recognition properties towards three xanthine derivatives were then explored through thermophoresis. Modifying the aptamer at position G11 led to binding inhibition. Modification at G25, however, changed the selectivity towards theobromine (Kd≈160 μm ), with a poor affinity for theophylline (Kd>1.5 mm ) being observed. Overall, 8-oxoG can have an impact on the structures of aptamers in a position-dependent manner, leading to altered target selectivity. 相似文献
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The role of a depressor factor, atrial natriuretic peptide, in the development of arterial hypertension in adolescents with pubertal hypothalamic syndrome was studied in 52 patients and 13 healthy males aged 13-24 years. The duration of disease was 2-11 years. Radioimmunological methods were used to measure plasma atrial natriuretic peptide, plasma renin activity, and serum aldosterone. Patients with borderline arterial hypertension were found to have a significant reduction in their atrial natriuretic peptide levels, and this correlated directly with the renin-aldosterone system, demonstrating insufficiency of the depressor system in patients with pubertal hypothalamic syndrome and the involvement of atrial natriuretic peptide in the development of arterial hypertension, along with disturbances in the functional relationship between atrial natriuretic peptide and the renin-aldosterone system. 相似文献
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G. Dell'Agli O. Marino G. Mascolo P. Pernice A. Di Chiara G. Pepe U. Scotti Di Uccio 《Journal of Materials Science: Materials in Electronics》1990,1(1):20-24
The thermal stability of the superconducting phase of nominal composition YBa2Cu3O7–x
-sintered pellets has been studied with respect to different temperatures (ranging from 300 to 950° C), time (ranging from 1 to 72 h), oxygen partial pressure (from 4 Pa to 1 atm) and carbon dioxide partial pressure (from 10–4 Pa to 1 atm). Annealed samples were characterized by X-ray diffraction analysis, optical microscopy, and resistive measurements of the superconductive transition temperature. A stability field of the orthorhombic and tetragonal phases was obtained, showing a region of coexistance. The decomposition of the 1 2 3 phase is found to be strongly influenced by the presence of a small amount of CO2 (1 p.p.m.) in the sintering atmosphere. A sintering process is proposed to avoid the formation of by-products. 相似文献
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The inhibition of squalene-hopene cyclase (SHC) (E.C. 5.4.99.-), an enzyme of bacterial membranes catalyzing the formation
of pentacyclic sterol-like triterpenes, was studied by using different classes of compounds originally developed as inhibitors
of oxidosqualene cyclase (OCS) (E.C. 5.4.99.7), the enzyme of eukaryotes responsible for the formation of tetracyclic precursors
of sterols. The mechanism of cyclization of squalene by SHC, beginning with a protonation of the 2,3 double bond by an acidic
residue of the enzyme, followed by a series of electrophilic additions of the carbocationic intermediates to the double bonds,
is similar to the mechanism of cyclization of 2,3-oxidosqualene by OSC. The inhibitors studied included: (i) analogs of the
carbocationic intermediates formed during cyclization, such as aza-analogs of squalene and 2,3-oxidosqualene; (ii) affinity-labeling
inhibitors bearing a methylidene reactive group; and (iii) vinyldioxidosqualenes and vinylsulfide derivatives of the substrates.
Comparison of the results obtained with the two enzymes, SHC and OSC, showed that many of the most effective inhibitors of
OSC were also able to inhibit SHC, while some derivatives acted as specific inhibitors. Differences could be easily explained
on the basis of the different substrate specificity of the two enzymes. 相似文献
8.
The sintering behaviour of SiC-Si and SiC-Si-WC composites hot-pressed via silicon liquid phase has been studied. The results show that the increase of silicon makes the sintered materials densify at lower temperature and the grain growth is restricted due to the effect of the liquid. The strength of SiC-25 vol.% Si samples is higher than the strength obtained for SiC-5 vol.% Si with the same hot-pressing conditions. The addition of WC particles improves relative densities and strengths of SiC-Si ceramics. 相似文献
9.
Oliaro-Bosso S Schulz-Gasch T Balliano G Viola F 《Chembiochem : a European journal of chemical biology》2005,6(12):2221-2228
A structural model of Saccharomyces cerevisiae oxidosqualene cyclase (SceOSC) suggests that some residues of the conserved sequence Pro-Ala-Glu-Val-Phe-Gly (residues 524-529) belong to a channel constriction that gives access to the active-site cavity. Starting from the SceOSC C457D mutant, which lacks the cysteine residue next to the catalytic Asp456 residue Cys457 has been replaced but Asp456 is still there, we prepared two further mutants where the wild-type residues Ala525 and Glu526 were individually replaced by cysteine. These mutants, especially E526C, were very sensitive to the thiol-reacting agent dodecyl-maleimide. Moreover, both the specific activity and the thermal stability of E526C were severely reduced. A similar decrease of the enzyme functionality was obtained by replacing Glu526 with alanine, while substitution with the conservative residues aspartate or glutamine did not alter catalytic activity. Molecular modeling of the yeast wild-type OSC and mutants on the template structure of human OSC confirms that the channel constriction is an important aspect of the protein structure and suggests a critical structural role for Glu526. 相似文献
10.
Francesca Arcelli Fontana Mika V. Mäntylä Marco Zanoni Alessandro Marino 《Empirical Software Engineering》2016,21(3):1143-1191
Several code smell detection tools have been developed providing different results, because smells can be subjectively interpreted, and hence detected, in different ways. In this paper, we perform the largest experiment of applying machine learning algorithms to code smells to the best of our knowledge. We experiment 16 different machine-learning algorithms on four code smells (Data Class, Large Class, Feature Envy, Long Method) and 74 software systems, with 1986 manually validated code smell samples. We found that all algorithms achieved high performances in the cross-validation data set, yet the highest performances were obtained by J48 and Random Forest, while the worst performance were achieved by support vector machines. However, the lower prevalence of code smells, i.e., imbalanced data, in the entire data set caused varying performances that need to be addressed in the future studies. We conclude that the application of machine learning to the detection of these code smells can provide high accuracy (>96 %), and only a hundred training examples are needed to reach at least 95 % accuracy. 相似文献