Effects of Prior Annealing on the Spark Plasma Sintering of Nanostructured Y2O3 Powders

The effects produced by annealing Y₂O₃ nanopowders on their spark plasma sintering (SPS) behavior are systematically investigated in this work. It is found that the annealed powders display higher sinterability with respect to the as‐received ones. Indeed, the maximum densification level reached from pristine powders is about 97.5%, whereas density decreases when further increasing either the sintering temperature or the dwell time. In contrast, the density of SPS products obtained from pretreated powder monotonically increases with temperature and processing time, thus leading to fully dense materials in 30 min at 1050°C and 60 MPa. Correspondingly, it is found that the annealing treatment markedly inhibits grain coarsening during SPS. Thus, dense translucent samples with grain size below 100 nm can be attained from annealed powders. On the other hand, white‐opaque specimens with significantly coarser microstructures (up to 1‐μm‐sized grains) are obtained when pristine powders are directly processed under the same sintering conditions. Furthermore, it is observed that the annealing treatment of SPS samples in air allows for graphite contamination removal, whereas no improvement in term of light transmittance is produced.     

Sofosbuvir Selects for Drug-Resistant Amino Acid Variants in the Zika Virus RNA-Dependent RNA-Polymerase Complex In Vitro

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.     

Intracranial and spinal dissemination of an ACTH secreting pituitary neoplasia. Case report and review of the literature

Smoking is associated with insulin resistance, dyslipidaemia and markers of the insulin resistance syndrome. This study investigated adipose tissue lipolysis in situ by subcutaneous microdialysis twice in 10 healthy, male smokers after smoking four cigarettes over 2 h and after the administration of an equal amount of nicotine given as nasal spray (NNS). Glucose and insulin levels, in situ lipolysis and adipose tissue blood flow were studied in the post-absorptive state and after a 75-g oral glucose tolerance test (OGTT). Post-absorptively, acute smoking and NNS increased neither subcutaneous adipose tissue glycerol production nor plasma free fatty acid (FFA) or glycerol levels. After the OGTT, plasma insulin and lactate levels were significantly higher after smoking, whereas FFA levels were higher after NNS. Normal smoking or the administration of a normal dose of NNS caused only minor metabolic changes. Thus, it does not seem likely that increased lipolysis is an important contributor to the dyslipidaemia seen in smokers.     

Dexamethasone inhibition of interferon-alpha 2-induced stimulation of cortisol and growth hormone secretion in chronic myeloproliferative syndrome

This study investigated the acute effects of interferon-alpha 2 (IFN-alpha 2) on hormonal secretion in adult patients affected by a chronic myeloproliferative syndrome and tried to shed some light on the mechanism by which IFN-alpha 2 stimulates cortisol and GH secretion in humans. We compared the pattern of IFN-alpha 2-induced cortisol and GH release with that elicited after the same challenge given subsequent to pretreatment with dexamethasone (Dex). We studied eight patients affected by a chronic myeloproliferative syndrome (thrombocythemia) who had been selected for treatment with IFN-alpha 2. Four sets of experiments were performed: 1) 2 mL iv saline was given at 0800 h in eight cases; 2) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h in eight cases; 3) 3 x 10(6) IU iv IFN-alpha 2 was given at 0800 h after pretreatment with 1.5 mg Dex (1 mg at midnight the previous night and 0.5 mg at 0700 h on the day of the test) in six cases; and 4) 2 mL iv saline was given at 0800 h after the same Dex pretreatment in four cases. Cortisol and GH were measured in plasma samples drawn at 30-min intervals between 0800 and 1300 h. Acute iv administration of IFN-alpha 2 stimulated the release of both cortisol and GH in each patient with a significant increment vs. control values, as assessed by areas under the curve. The administration of Dex significantly decreased basal plasma cortisol secretion and abolished cortisol response to IFN-alpha 2 administration. These data suggest that the stimulatory action of IFN-alpha 2 on cortisol release is mediated via a modulation of the activity of the hypothalamic-pituitary axis rather than through a direct effect at the level of the adrenal cortex. After Dex plus saline administration, no significant effect was observed on plasma GH levels, which remained low. Dex administration significantly decreased GH response to IFN-alpha 2. These data suggest that a hypothalamic or pituitary stimulation (or both) is involved in the mechanism of IFN-alpha 2-induced GH secretion. It remains to be established whether IFN-alpha 2 directly stimulates pituitary somatotropic cells or whether the cytokine exerts a stimulatory action on GH secretion by indirectly modulating the hypothalamic or pituitary activity. In conclusion, acute iv administration of IFN-alpha 2 represents a potent stimulus for cortisol and GH secretion in adult human subjects.(ABSTRACT TRUNCATED AT 400 WORDS)     

Vibrational analysis of functionalized polyolefins/poly(vinylchloride) blends

Polyolefins functionalized with diethylmaleate were mixed with poly(vinylchloride) (PVC) in different compositions. Intermolecular interactions involving the carbonyl groups of the side chains of the functionalized polyolefins and methine hydrogens of PVC were investigated by means of infrared spectroscopy. The major flexibility of the ester groups attached to the backbone chains, with respect to polyesters, seems to increase the capability of such groups to interact with groups of more polar polymers, thus allowing prediction of easier miscibility, which however also depends on the starting polyolefin structure and function-alization degree.     

Fault-accommodation with intelligent sensors

Optimal sensor fault-accommodation is considered for faults modelled by an increase in measurement noise. This noise is taken to be bounded and its probabilistic properties unknown. It is assumed that intelligent (e.g. self-validating) instrumentation is in use and estimates of the noise bounds are available. The fault-tolerant controller is designed to optimize a noise rejection and a nominal reference tracking index and leads to a mixed norm minimization problem (l₁/l₂). We exploit known results and a particular feedback configuration to show that it is possible to optimize simultaneously without a trade-off the two performance indices. The results are applied to systems where the presence of auxiliary measurements allows for an optimal fault-accommodation strategy. Using properties of the optimal solution, we define a factorization for the optimal controller alternative to the Youla parametrization, leading to an algorithm which is optimal, transparent and efficient.     

Analysis of the MSS51 region on chromosome XII of Saccharomyces cerevisiae.

We have localized gene MSS51 on chromosome XII of Saccharomyces cerevisiae between the RDN1 and CDC42 loci. 'Head to head' with MSS51 is another gene, QRI5, the function of which is unknown. However, the proximity of these genes, the structure of the intergenic region and the presence of an ABF1 binding site right in the middle of this region suggest that the MSS51 and QRI5 expressions are submitted to a common regulatory process.