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81.
Multimedia Tools and Applications - In this paper, we will present a study concerning the understanding of the needs of people using Internet in order to access to multilingual information. In...  相似文献   
82.
The objective is to analyse how one's place of residence affects the probability of finding a job and to measure the definition of the public jobcentre catchment area, which contributes to improving labour outcomes in the most deprived areas. We propose a multilevel model to estimate the probability of finding a job controlling for individual characteristics and discerning the effect of the place of residence and the contribution of public employment centres. We use an administrative register of jobseekers (70,379) grouped by 384 postal codes and 24 jobcentres. The econometric results confirm the hypothesis that there is a strong residence effect that is not sufficiently mitigated by public employment services.  相似文献   
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We prepared the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla, 1 ) in multigram scale by asymmetric hydrogenation. These amino acids, protected as Fmoc derivatives, were then used in the solid‐phase synthesis of two new somatostatin 14 (SRIF‐14) analogues 8 a and 8 b , tetradecapeptides in which the tryptophan residue (Trp8) is replaced by one of the two enantiomers of 3‐(3′‐quinolyl)‐alanine (Qla8) and therefore lack the N? H bond in residue 8. The selectivity of these new analogues for the somatostatin receptors, SSTR1–5, was measured. Substitution with L ‐Qla8 yielded peptide 8 a , which was highly selective for SSTR1 and SSTR3, with an affinity similar to that of SRIF‐14. Substitution by D ‐Qla gave the relatively selective analogue 8 b , which showed high affinity for SSTR3 and significant affinity for SSTR1, SSTR2 and SSTR5. The biological results demonstrate that bulky and electronically poor aromatic amino acids at position 8 are compatible with strong activity with SSTR1 and SSTR3. Remarkably, these high affinity levels were achieved with peptides in which the conformational mobility was increased with respect to that of SRIF‐14. This observation suggests that conformational rigidity is not required, and might be detrimental to the interaction with receptors SSTR1 and SSTR3. The absence of an indole N proton in Qla8 might also contribute to the increased flexibility observed in these analogues.  相似文献   
86.
DsbA enzymes catalyze oxidative folding of proteins that are secreted into the periplasm of Gram-negative bacteria, and they are indispensable for the virulence of human pathogens such as Vibrio cholerae and Escherichia coli. Therefore, targeting DsbA represents an attractive approach to control bacterial virulence. X-ray crystal structures reveal that DsbA enzymes share a similar fold, however, the hydrophobic groove adjacent to the active site, which is implicated in substrate binding, is shorter and flatter in the structure of V. cholerae DsbA (VcDsbA) compared to E. coli DsbA (EcDsbA). The flat and largely featureless nature of this hydrophobic groove is challenging for the development of small molecule inhibitors. Using fragment-based screening approaches, we have identified a novel small molecule, based on the benzimidazole scaffold, that binds to the hydrophobic groove of oxidized VcDsbA with a KD of 446±10 μM. The same benzimidazole compound has ∼8-fold selectivity for VcDsbA over EcDsbA and binds to oxidized EcDsbA, with KD>3.5 mM. We generated a model of the benzimidazole complex with VcDsbA using NMR data but were unable to determine the structure of the benzimidazole bound EcDsbA using either NMR or X-ray crystallography. Therefore, a structural basis for the observed selectivity is unclear. To better understand ligand binding to these two enzymes we crystallized each of them in complex with a known ligand, the bile salt sodium taurocholate. The crystal structures show that taurocholate adopts different binding poses in complex with VcDsbA and EcDsbA, and reveal the protein-ligand interactions that stabilize the different modes of binding. This work highlights the capacity of fragment-based drug discovery to identify inhibitors of challenging protein targets. In addition, it provides a starting point for development of more potent and specific VcDsbA inhibitors that act through a novel anti-virulence mechanism.  相似文献   
87.
Begoña Rubio  Ana Maria Mastral 《Fuel》1985,64(8):1127-1131
The aromatic fraction of oils obtained by catalytic depolymerization of a Spanish subbituminous coal has been separated by means of liquid chromatography on partially deactivated alumina into six subfractions, which were studied by i.r. and 1H n.m.r. spectroscopy. The results indicate hydroaromatic structures with a low degree of condensation, with one to three aromatic nuclei on average, short chain alkyl substituents and significant amounts of -OH and aromatic ether groups.  相似文献   
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Food allergens are a real threat to sensitized individuals. Although food labeling is crucial to provide information to consumers with food allergies, accidental exposure to allergenic proteins may result from undeclared allergenic substances by means of food adulteration, fraud or uncontrolled cross-contamination. Allergens detection in foodstuffs can be a very hard task, due to their presence usually in trace amounts, together with the natural interference of the matrix. Methods for allergens analysis can be mainly divided in two large groups: the immunological assays and the DNA-based ones. Mass spectrometry has also been used as a confirmatory tool. Recently, biosensors appeared as innovative, sensitive, selective, environmentally friendly, cheaper and fast techniques (especially when automated and/or miniaturized), able to effectively replace the classical methodologies. In this review, we present the advances in the field of food allergens detection toward the biosensing strategies and discuss the challenges and future perspectives of this technology.  相似文献   
90.
In vitro antioxidant activity of red grape skins   总被引:1,自引:0,他引:1  
Phenolic antioxidants seem to be partly responsible for the protective effects against cardiovascular diseases attributed to moderate wine consumption. Grape skins greatly contribute to the phenolic composition of red wine. In this paper, the in vitro antioxidant activity of red grape (Vitis vinifera) skins is determined. We show that the radical scavenging activity (C 50 values) against 2,2-diphenyl-1-picrylhydrazyl (DPPH·) of grape skin extracts is relatively high (3.2–11.1 mg dried skin/mg DPPH·) in relation to other foodstuffs and, as expected, is influenced by grape variety, stage of grape ripening and vintage. The antioxidant potential of grape skins seems to be transferred into wine since grape varieties with skins exhibiting high antioxidant potential also resulted in wines with high antioxidant activity. Statistically significant correlations were found between antioxidant activity and phenolic content (total polyphenols, proanthocyanins, catechins and anthocyanins) for both grape skins and wines.  相似文献   
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