Enhancing cultural recommendations through social and linked open data

In this article, we describe a hybrid recommender system (RS) in the artistic and cultural heritage area, which takes into account the activities on social media performed by the target user and her friends, and takes advantage of linked open data (LOD) sources. Concretely, the proposed RS (1) extracts information from Facebook by analyzing content generated by users and their friends; (2) performs disambiguation tasks through LOD tools; (3) profiles the active user as a social graph; (4) provides her with personalized suggestions of artistic and cultural resources in the surroundings of the user’s current location. The last point is performed by integrating collaborative filtering algorithms with semantic technologies in order to leverage LOD sources such as DBpedia and Europeana. Based on the recommended points of cultural interest, the proposed system is also able to suggest to the active user itineraries among them, which meet her preferences and needs and are sensitive to her physical and social contexts as well. Experimental results on real users showed the effectiveness of the different modules of the proposed recommender.

     

Effects of Lipidation on a Proline-Rich Antibacterial Peptide

The emergence of multidrug-resistant bacteria is a worldwide health problem. Antimicrobial peptides have been recognized as potential alternatives to conventional antibiotics, but still require optimization. The proline-rich antimicrobial peptide Bac7(1-16) is active against only a limited number of Gram-negative bacteria. It kills bacteria by inhibiting protein synthesis after its internalization, which is mainly supported by the bacterial transporter SbmA. In this study, we tested two different lipidated forms of Bac7(1-16) with the aim of extending its activity against those bacterial species that lack SbmA. We linked a C12-alkyl chain or an ultrashort cationic lipopeptide Lp-I to the C-terminus of Bac7(1-16). Both the lipidated Bac-C12 and Bac-Lp-I forms acquired activity at low micromolar MIC values against several Gram-positive and Gram-negative bacteria. Moreover, unlike Bac7(1-16), Bac-C12, and Bac-Lp-I did not select resistant mutants in E. coli after 14 times of exposure to sub-MIC concentrations of the respective peptide. We demonstrated that the extended spectrum of activity and absence of de novo resistance are likely related to the acquired capability of the peptides to permeabilize cell membranes. These results indicate that C-terminal lipidation of a short proline-rich peptide profoundly alters its function and mode of action and provides useful insights into the design of novel broad-spectrum antibacterial agents.     

Synthesis,Molecular Modeling and Biological Evaluation of Metabolically Stable Analogues of the Endogenous Fatty Acid Amide Palmitoylethanolamide

Palmitoylethanolamide (PEA) belongs to the class of N-acylethanolamine and is an endogenous lipid potentially useful in a wide range of therapeutic areas; products containing PEA are licensed for use in humans as a nutraceutical, a food supplement, or food for medical purposes for its analgesic and anti-inflammatory properties demonstrating efficacy and tolerability. However, the exogenously administered PEA is rapidly inactivated; in this process, fatty acid amide hydrolase (FAAH) plays a key role both in hepatic metabolism and in intracellular degradation. So, the aim of the present study was the design and synthesis of PEA analogues that are more resistant to FAAH-mediated hydrolysis. A small library of PEA analogues was designed and tested by molecular docking and density functional theory calculations to find the more stable analogue. The computational investigation identified RePEA as the best candidate in terms of both synthetic accessibility and metabolic stability to FAAH-mediated hydrolysis. The selected compound was synthesized and assayed ex vivo to monitor FAAH-mediated hydrolysis and to confirm its anti-inflammatory properties. ¹H-NMR spectroscopy performed on membrane samples containing FAAH in integral membrane protein demonstrated that RePEA is not processed by FAAH, in contrast with PEA. Moreover, RePEA retains PEA’s ability to inhibit LPS-induced cytokine release in both murine N9 microglial cells and human PMA-THP-1 cells.     

A2B Adenosine Receptors: When Outsiders May Become an Attractive Target to Treat Brain Ischemia or Demyelination

Adenosine is a signaling molecule, which, by activating its receptors, acts as an important player after cerebral ischemia. Here, we review data in the literature describing A_2BR-mediated effects in models of cerebral ischemia obtained in vivo by the occlusion of the middle cerebral artery (MCAo) or in vitro by oxygen-glucose deprivation (OGD) in hippocampal slices. Adenosine plays an apparently contradictory role in this receptor subtype depending on whether it is activated on neuro-glial cells or peripheral blood vessels and/or inflammatory cells after ischemia. Indeed, A_2BRs participate in the early glutamate-mediated excitotoxicity responsible for neuronal and synaptic loss in the CA1 hippocampus. On the contrary, later after ischemia, the same receptors have a protective role in tissue damage and functional impairments, reducing inflammatory cell infiltration and neuroinflammation by central and/or peripheral mechanisms. Of note, demyelination following brain ischemia, or autoimmune neuroinflammatory reactions, are also profoundly affected by A_2BRs since they are expressed by oligodendroglia where their activation inhibits cell maturation and expression of myelin-related proteins. In conclusion, data in the literature indicate the A_2BRs as putative therapeutic targets for the still unmet treatment of stroke or demyelinating diseases.     

Water soluble trehalose-derived oligoamides

A new family of oligotrehaluronamides was synthesized through the polycondensation of α,α-trehaluronic acid dimethyl ester and different diamines or polyamines. In particular, diamines with different molecular structure (1,n-alkylene diamines, aromatic diamine, and alkyleneoxydiamine) were used in order to modulate the molecular weights and the physical characteristics of the products, such as T_g, hydrophilic or hydrophobic properties, and solubility. α,α-Trehaluronic acid was obtained from a renewable source as α,α-trehalose. The syntheses of oligotrehaluronamides were carried out in different solvents such as ethanol, methanol, THF and DMSO, using triethylamine as catalyst. All the compounds obtained in this study were characterized through FT-IR and NMR spectroscopy. The molecular weights were evaluated by ¹H-NMR and in some cases compared with those obtained from ESI-MS spectrometry. Glass transition temperatures and melting points were detected by differential scanning calorimetry. Low molecular weight oligoamides, containing several hydroxyl groups, are water-soluble and could be used in water-based formulations.     

Inflammatory Cutaneous Diseases in Renal Transplant Recipients

Kidney transplant recipients frequently suffer from skin infections and malignancies, possibly due to the effects of long-term immunosuppressive therapy. While the relationships between immunosuppression and these pathological conditions have been widely investigated, little is known about the relative incidence and characteristics of inflammatory skin diseases in this type of patient. In this study, we analyze the incidence of a number of inflammatory cutaneous diseases in a cohort of patients who underwent kidney transplantation. Although our study shows a relatively low incidence of these pathologies in transplanted patients—in agreement with the general action of immunosuppressant therapies in reducing inflammation—we scored a different efficacy of the various immunosuppressive regimens on inflammatory and autoimmune skin diseases. This information can be key for designing immunosuppressive regimens and devising accurate follow-up protocols.     

Designing Dual Transglutaminase 2/Histone Deacetylase Inhibitors Effective at Halting Neuronal Death

In recent years there has been a clear consensus that neurodegenerative conditions can be better treated through concurrent modulation of different targets. Herein we report that combined inhibition of transglutaminase 2 (TG2) and histone deacetylases (HDACs) synergistically protects against toxic stimuli mediated by glutamate. Based on these findings, we designed and synthesized a series of novel dual TG2–HDAC binding agents. Compound 3 [(E)‐N‐hydroxy‐5‐(3‐(4‐(3‐oxo‐3‐(pyridin‐3‐yl)prop‐1‐en‐1‐yl)phenyl)thioureido)pentanamide] emerged as the most interesting of the series, being able to inhibit TG2 and HDACs both in vitro (TG2 IC₅₀=13.3±1.5 μm , HDAC1 IC₅₀=3.38±0.14 μm , HDAC6 IC₅₀=4.10±0.13 μm ) and in cell‐based assays. Furthermore, compound 3 does not exert any toxic effects in cortical neurons up to 50 μm and protects neurons against toxic insults induced by glutamate (5 mm ) with an EC₅₀ value of 3.7±0.5 μm .     

Room-Temperature Degradation of t-Zr(Pr)O2 in an Aqueous Suspension Revealed by Perturbed Angular Correlations

This paper deals with the phase stability of an aqueous suspension of tetragonal Zr_0.9Pr_0.1O₂ (20 wt%/vol%) at room temperature as a function of the aging time. The suspension is investigated in situ using the highly localized Perturbed Angular Correlations technique. The results indicate that an almost fully reversible degradation process toward monoclinic zirconia takes place through a first-order reaction of rate constant k =0.7 day⁻¹. Two successive diffusion mechanisms are observed that are interpreted as OH⁻ ions' migration in the grain surface and then, as proton defects' diffusion into the bulk.     

Probabilistic measurement evaluation for the implementation of the Measuring Instrument Directive

The approval of the European Measuring Instrument Directive (2004) constitutes a noteworthy novelty in legal metrology, since this Directive implements the so called “new approach” to technical normalization and harmonization and moves toward a “global approach” to evaluation and conformity. According to the principles of the new approach regulatory model, the Directive establishes some essential requirements for a wide class of measuring devices, subject to legal control, whilst leaving manufacturer free to develop proper technical solutions for meeting them. Moreover, the conformity of instruments to prescribed requirement may now be ensured through quality assurance procedures, in the context of a quality system. This increase in technical and metrological freedom on the manufactures side may promote innovation, social benefit and costumers’ satisfaction, provided that some recent advances in measurement theory are properly employed.In this paper, after a brief discussion regarding the philosophy of the Directive, a probabilistic approach to conformity assessment is presented. The proposed approach concerns some currently open issues such as measurement uncertainty due to the influence of operating conditions, the assessment and reduction of the risk related to measurement uncertainty in conformity decision and the costs of instrument uncertainty and of non-conformity, for both the manufacturer and the user. The approach is supported by a package of software codes that assists the application of verification procedures, with a user-friendly approach.All these aspects are discussed with reference to the case of water meters, considering both end-of-production acceptance tests and the performance of meters under operation.     

Effective wind actions on ideal and real structures

Gust buffeting of structures is analyzed by Double Modal Transformation, a method consisting in the joint transformation into principal components of structural displacements (modal analysis) and of wind loading (proper orthogonal decomposition). It commonly occurs that modal truncation applies to both the series of structural and loading modes; besides, many loading modes are almost orthogonal respect the dominant structural modes, so they do not contribute to structural response. This set of conditions allows the introduction of an effective action, defined as the loading process reconstructed retaining only those loading modes that excite the structure. This paper discusses this method and the related concepts by analyzing a set of simple ideal structures in closed form; this approach allows the formulation of general criteria aimed at defining the effective wind action as a function of non-dimensional structural and wind parameters. The numerical analysis of a real structure confirms the tendencies pointed out by the analytical solutions.