The puzzling afterglow of GRB 050721: a rebrightening seen in the optical but not in the X-ray

We present here the analysis of the early and late multiwavelength afterglow emission, as observed by Swift a small robotic telescope and very large telescope (VLT). We compare early observations with late afterglow observations obtained with Swift and the VLT and we observe an intense rebrightening in the optical band at about 1 day after the burst, which is not present in the X-ray band. The lack of detection in X-ray of such a strong rebrightening at lower energies may be described with a variable external density profile. In such a scenario, the combined X-ray and optical observations allow us to derive that the matter density located at approximately 1017 cm from the burst is approximately a factor of 10 higher than in the inner region. This is the first time in which a rebrightening has been observed in the optical afterglow of a gamma-ray burst that is clearly absent in the X-ray afterglow.     

Solid lipid nanoparticles incorporating melatonin as new model for sustained oral and transdermal delivery systems

melatonin (MT) is a hormone produced by the pineal gland at night, involved in the regulation of circadian rhythms. For clinical purposes, exogenous MT administration should mimic the typical nocturnal endogenous MT levels, but its pharmacokinetics is not favourable due to short half-life of elimination. Aim of this study is to examine pharmacokinetics of MT incorporated in solid lipid nanoparticles (SLN), administered by oral and transdermal route. SLN peculiarity consists in the possibility of acting as a reservoir, permitting a constant and prolonged release of the drugs included. In 7 healthy subjects SLN incorporating MT 3 mg (MT-SLN-O) were orally administered at 8.30 a.m. MT 3 mg in standard formulation (MT-S) was then administered to the same subjects after one week at 8.30 a.m. as controls. In 10 healthy subjects SLN incorporating MT were administered transdermally (MT-SLN-TD) by the application of a patch at 8.30 a.m. for 24 hours. Compared to MT-S, Tmax after MT-SLN-O administration resulted delayed of about 20 minutes, while mean AUC and mean half life of elimination was significantly higher (respectively 169944.7 +/- 64954.4 pg/ml x hour vs. 85148.4 +/- 50642.6 pg/ml x hour, p = 0.018 and 93.1 +/- 37.1 min vs. 48.2 +/- 8.9 min, p = 0.009). MT absorption and elimination after MT-SLN-TD demonstrated to be slow (mean half life of absorption: 5.3 +/- 1.3 hours; mean half life of elimination: 24.6 +/- 12.0 hours), so MT plasma levels above 50 pg/ml were maintained for at least 24 hours. This study demonstrates a significant absorption of MT incorporated in SLN, with detectable plasma level achieved for several hours in particular after transdermal administration. As dosages and concentrations of drugs included in SLN can be varied, different plasma level profile could be obtained, so disclosing new possibilities for sustained delivery systems.     

A Tabu-search-based Algorithm for Distribution Network Restoration to Improve Reliability and Resiliency

Fault restoration techniques have always been crucial for distribution system operators（DSOs）. In the last decade, it started to gain more and more importance due to the introduction of output-based regulations where DSO performances are evaluated according to frequency and duration of energy supply interruptions. The paper presents a tabu-searchbased algorithm able to assist distribution network operational engineers in identifying solutions to restore the energy supply after permanent faults. According to the network property, two objective functions are considered to optimize either reliability or resiliency. The mathematical formulation includes the traditional feeders, number of switching operation limit, and radiality constraints. Thanks to the DSO of Milan, Unareti, the proposed algorithm has been tested on a real distribution network to investigate its effectiveness.     

2-Phenyloxazole-4-carboxamide as a Scaffold for Selective Inhibition of Human Monoamine Oxidase B

A series of 2-phenyloxazoles bearing an amide group at position 4 were designed and synthesized for evaluation as potential inhibitors of human recombinant monoamine oxidases (hrMAOs). Results of kinetics experiments demonstrated that all compounds behave as competitive MAO inhibitors, with good selectivity toward the MAO-B isoform. The most potent and selective derivatives are characterized by inhibition constant (K_i) values in the sub-micromolar range and a good selectivity index (K_{i MAO-A}/K_{i MAO-B}>50). Some derivatives were also found to be able to inhibit MAO activity in nerve growth factor (NGF)-differentiated PC12 cells, taken as a model of neuronal cells. In particular, 2-(2-hydroxyphenyl)-N-phenyloxazole-4-carboxamide (compound 4 a ) may be a promising new scaffold, exerting the highest selectivity and inhibitory effect toward MAOs in NGF-differentiated PC12 cell lysates, without compromising cell viability. Molecular docking analysis allowed a rationalization of the experimentally observed binding affinity and selectivity.