Biomimetic Citrate-Coated Luminescent Apatite Nanoplatforms for Diclofenac Delivery in Inflammatory Environments

Luminescent nanoparticles are innovative tools for medicine, allowing the imaging of cells and tissues, and, at the same time, carrying and releasing different types of molecules. We explored and compared the loading/release ability of diclofenac (COX-2 antagonist), in both undoped- and luminescent Terbium3+ (Tb3+)-doped citrate-coated carbonated apatite nanoparticles at different temperatures (25, 37, 40 \ub0C) and pHs (7.4, 5.2). The cytocompatibility was evaluated on two osteosarcoma cell lines and primary human osteoblasts. Biological effects of diclofenac-loaded-nanoparticles were monitored in an in vitro osteoblast\u2019s cytokine\u2013induced inflammation model by evaluating COX-2 mRNA expression and production of PGE2. Adsorption isotherms fitted the multilayer Langmuir-Freundlich model. The maximum adsorbed amounts at 37 \ub0C were higher than at 25 \ub0C, and particularly when using the Tb3+ -doped particles. Diclofenac-release efficiencies were higher at pH 5.2, a condition simulating a local inflammation. The luminescence properties of diclofenac-loaded Tb3+ -doped particles were affected by pH, being the relative luminescence intensity higher at pH 5.2 and the luminescence lifetime higher at pH 7.4, but not influenced either by the temperature or by the diclofenac-loaded amount. Both undoped and Tb3+-doped nanoparticles were cytocompatible. In addition, diclofenac release increased COX-2 mRNA expression and decreased PGE2 production in an in vitro inflammation model. These findings evidence the potential of these nanoparticles for osteo-localized delivery of anti-inflammatory drugs and the possibility to localize the inflammation, characterized by a decrease in pH, by changes in luminescence

Update on the correlation of the highest energy cosmic rays with nearby extragalactic matter

Data collected by the Pierre Auger Observatory through 31 August 2007 showed evidence for anisotropy in the arrival directions of cosmic rays above the Greisen-Zatsepin-Kuz'min energy threshold, \nobreak{$6\times 10^{19}$eV}. The anisotropy was measured by the fraction of arrival directions that are less than $3.1^\circ$ from the position of an active galactic nucleus within 75 Mpc (using the V\'eron-Cetty and V\'eron $12^{\rm th}$ catalog). An updated measurement of this fraction is reported here using the arrival directions of cosmic rays recorded above the same energy threshold through 31 December 2009. The number of arrival directions has increased from 27 to 69, allowing a more precise measurement. The correlating fraction is $(38^{+7}_{-6})$, compared with $21$ expected for isotropic cosmic rays. This is down from the early estimate of $(69^{+11}_{-13})$. The enlarged set of arrival directions is examined also in relation to other populations of nearby extragalactic objects: galaxies in the 2 Microns All Sky Survey and active galactic nuclei detected in hard X-rays by the Swift Burst Alert Telescope. A celestial region around the position of the radiogalaxy Cen A has the largest excess of arrival directions relative to isotropic expectations. The 2-point autocorrelation function is shown for the enlarged set of arrival directions and compared to the isotropic expectation.Comment: Accepted for publication in Astroparticle Physics on 31 August 201

Spatio-temporal Object-Oriented Bayesian Network modelling of the COVID-19 Italian outbreak data

The spatial epidemic dynamics of COVID-19 outbreak in Italy were modelled by means of an Object-Oriented Bayesian Network in order to explore the dependence relationships, in a static and a dynamic way, among the weekly incidence rate, the intensive care units occupancy rate and that of deaths. Following an autoregressive approach, both spatial and time components have been embedded in the model by means of spatial and time lagged variables. The model could be a valid instrument to support or validate policy makers\u2019 decisions strategies

Wavelet-based Self-Organizing Maps for classifying multivariate time series

Following a nonparametric approach, we suggest a time series clustering method. Our clustering approach combines the benefits connected to the interpretative power of the nonparametric representation of the time series, and the clustering and vector quantization informational gain produced by the adopted unsupervised neural networks technique, enhanced with the Self-Organizing Maps ordering and topological preservation abilities. The proposed clustering method takes into account a composite wavelet-based information of the multivariate time series by adding to the information connected to the wavelet variance, viz., the influence of variability of individual univariate components of the multivariate time series across scales, the information associated to wavelet correlation, represented by the interaction between pairs of univariate components of the multivariate time series at each scale, and then suitably tuning the combination of these pieces of information. In order to assess the effectiveness of the proposed clustering approach a simulation study and an empirical application are shown

Structure of regional dykes and local cone sheets in the Midhyrna-Lysuskard area, Snaefellsnes Peninsula (NW Iceland).

This paper provides the first detailed structural description of 48 vertical dykes, 384 inclined sheets and two large intrusions and the geometry (strike, dip direction and dip) of 1116 fractures in the central area of the Snaefellsnes peninsula, NW Iceland. Our data show a more complex set- ting than that depicted by the WNW-ESE en-echelon trend of the volcanic structures at the surface. In the Miocene basement lavas, dykes dominantly strike N50\u2013100\ub0E whereas other directions are also present with a higher dispersion. Two main swarms of centrally dipping sheets have also been recog- nized, focussing towards two areas. Sheet dips range from 2 to 75\ub0 with the higher frequency between 10 and 45\ub0. In section view, there is no systematic variation of sheet dip with dis- tance from the focus area. Gabbro and granophyre laccoliths are present in the studied area but cross-cutting relations indicate that most of the inclined sheets are younger. Compar- ison with regional tectonics suggests that the N50\u201380\ub0E-strik- ing dykes are coherent with emplacement under the stress field of the pre-6 Ma Snaefellsnes Rift dominated by a NNW-SSE-directed least principal stress (!3). The N80\u2013 100\ub0E dykes and the late Quaternary WNW-trending sub- aerial volcanic features are instead consistent with the devel- opment of a more recent E-W, right-lateral shear zone affecting the Snaefellsnes peninsula. Coherent sets of fractures have also been found. Within the inclined sheet swarms, the stress tensor rotated in response to an excess magma pressure linked to two underlying magma chambers of lobate shape, located at an estimated depth of about 400 and 500 m below sea level. This local magmatic stress also produced the cen- trally inclined fracture swarms that have been found in this area

Well\u2011Being in the Italian Regions Over Time

In this paper, we define clusters of homogeneous Italian regions with respect to the evolution over time of well-being. In particular we identify three partitions of the Italian regions based on the yearly time series of the economic, social and environmental dimensions of the BES (equitable and sustainable well-being), in the period 2010\u20132016. The partitions are obtained using a Dynamic Time Warping-based Fuzzy C-Medoids clustering model for multivariate time series. The results show a territorial gap between northern and southern regions with respect to the economic, social and environmental dimensions. The central regions have a diversified behavior with respect to the different dimensions