455 research outputs found

    Experimental evidence of delocalized states in random dimer superlattices

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    We study the electronic properties of GaAs-AlGaAs superlattices with intentional correlated disorder by means of photoluminescence and vertical dc resistance. The results are compared to those obtained in ordered and uncorrelated disordered superlattices. We report the first experimental evidence that spatial correlations inhibit localization of states in disordered low-dimensional systems, as our previous theoretical calculations suggested, in contrast to the earlier belief that all eigenstates are localized.Comment: 4 pages, 5 figures. Physical Review Letters (in press

    GPR17: Molecular modeling and dynamics studies of the 3-D structure and purinergic ligand binding features in comparison with P2Y receptors

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    <p>Abstract</p> <p>Background</p> <p>GPR17 is a G-protein-coupled receptor located at intermediate phylogenetic position between two distinct receptor families: the P2Y and CysLT receptors for extracellular nucleotides and cysteinyl-LTs, respectively. We previously showed that GPR17 can indeed respond to both classes of endogenous ligands and to synthetic compounds active at the above receptor families, thus representing the first fully characterized non-peptide "hybrid" GPCR. In a rat brain focal ischemia model, the selective <it>in vivo </it>knock down of GPR17 by anti-sense technology or P2Y/CysLT antagonists reduced progression of ischemic damage, thus highlighting GPR17 as a novel therapeutic target for stroke. Elucidation of the structure of GPR17 and of ligand binding mechanisms are the necessary steps to obtain selective and potent drugs for this new potential target. On this basis, a 3-D molecular model of GPR17 embedded in a solvated phospholipid bilayer and refined by molecular dynamics simulations has been the first aim of this study. To explore the binding mode of the "purinergic" component of the receptor, the endogenous agonist UDP and two P2Y receptor antagonists demonstrated to be active on GPR17 (MRS2179 and cangrelor) were then modeled on the receptor.</p> <p>Results</p> <p>Molecular dynamics simulations suggest that GPR17 nucleotide binding pocket is similar to that described for the other P2Y receptors, although only one of the three basic residues that have been typically involved in ligand recognition is conserved (Arg255). The binding pocket is enclosed between the helical bundle and covered at the top by EL2. Driving interactions are H-bonds and salt bridges between the 6.55 and 6.52 residues and the phosphate moieties of the ligands. An "accessory" binding site in a region formed by the EL2, EL3 and the Nt was also found.</p> <p>Conclusion</p> <p>Nucleotide binding to GPR17 occurs on the same receptor regions identified for already known P2Y receptors. Agonist/antagonist binding mode are similar, but not identical. An accessory external binding site could guide small ligands to the deeper principal binding site in a multi-step mechanism of activation. The nucleotide binding pocket appears to be unable to allocate the leukotrienic type ligands in the same effective way.</p

    The labor productivity slowdown: the true issue of the Italian Economy

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    This paper deals with the issue of the weak growth in Italian labor productivity with particular reference to the period between 2000 and 2016. In analyzing the data relat-ing to labor productivity, the influence of capital productivity and multifactor produc-tivity were also considered. The analysis shows how the weak growth in labor produc-tivity is due to some peculiar structural aspects of the Italian production system. At the end of the paper some comments are offered on possible policy interventions

    Corporate Governance, dimensioni ed efficienza del settore bancario italiano

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    The Corporate Governance is supposed to influence significantly the economic performances of the firms. This paper investigates on the effects that some variables - like characteristics of the board director, the potential conflict of interest, the stock option - have on the economic results of a sample of Italian banks. The results of the analysis suggest that this variables, with others related to the scale, do matter

    The Dual Behaviour of a GPCR Involved in Brain Damage an Repair: Forced Unbinding of the Receptor GPR17 Ligands from Wild Type and R255I Mutant Models Through a Computational Approach

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    GPR17 is a hybrid G-protein-coupled receptor activated by two unrelated ligand families, extracellular nucleotides and cysteinyl-leukotrienes, and involved in brain damage and repair. Its exploitment as a target for novel neuroreparative strategies depends on the elucidation of the molecular determinants driving binding of its ligands. We applied docking and molecular dynamics simulations to analyse the binding and the forced unbinding of two GPR17 ligands (the purinergic agonist UDP and the leukotriene receptor antagonist pranlukast) from both the wild-type receptor and a mutant model, where a basic residue hypothesized to be crucial for nucleotide binding had been mutated (R255I). Molecular dynamics suggested that GPR17 nucleotide binding pocket is enclosed between the helical bundle and EL2. The driving interaction involves R255 and the UDP phosphate moiety. Steered molecular dynamics experiments showed that the energy required to unbind UDP is higher for the wild-type receptor than for R255I. Three potential binding sites for pranlukast were found. In one of its preferential docking conformations, pranlukast tetrazole group is close to R255 and phenyl rings are placed into a subpocket highly conserved among GPCRs. Pulling forces developed to break polar and aromatic interactions of pranlukast were comparable. No differences between the wild-type receptor and the R255I receptor were found for the unbinding of pranlukast. These data suggest a crucial role for R255 in binding of nucleotides to GPR17. Aromatic interactions are instead likely to play a predominant role in the recognition of pranlukast, suggesting that two different binding subsites are present on GPR17

    Identification of serine/threonine kinase and nucleotide-binding site–leucine-rich repeat (NBS-LRR) genes in the fire blight resistance quantitative trait locus of apple cultivar ‘Evereste’

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    Fire blight is the most destructive bacterial disease affecting apple (Malus×domestica) worldwide. So far, no resistance gene against fire blight has been characterized in apple, despite several resistance regions having been identified. A highly efficacious resistance quantitative trait locus (QTL) was localized on linkage group 12 (LG12) of the ornamental cultivar ‘Evereste’. A marker previously reported to be closely linked to this resistance was used to perform a chromosome landing. A bacterial artificial chromosome (BAC) clone of 189 kb carrying the fire blight resistance QTL was isolated and sequenced. New microsatellite markers were developed, and the genomic region containing the resistance locus was limited to 78 kb. A cluster of eight genes with homologies to already known resistance gene structures to bacterial diseases was identified and the corresponding gene transcription was verified. From this cluster, two genes were recognized in silico as the two most probable fire blight resistance genes showing homology with the Pto/Prf complex in tomato

    Lax-Phillips Scattering Theory of a Relativistic Quantum Field Theoretical Lee-Friedrichs Model and Lee-Oehme-Yang-Wu Phenomenology

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    The one-channel Wigner-Weisskopf survival amplitude may be dominated by exponential type decay in pole approximation at times not too short or too long, but, in the two channel case, for example, the pole residues are not orthogonal, and the pole approximation evolution does not correspond to a semigroup (experiments on the decay of the neutral K-meson system support the semigroup evolution postulated by Lee, Oehme and Yang, and Yang and Wu, to very high accuracy). The scattering theory of Lax and Phillips, originally developed for classical wave equations, has been recently extended to the description of the evolution of resonant states in the framework of quantum theory. The resulting evolution law of the unstable system is that of a semigroup, and the resonant state is a well-defined funtion in the Lax-Phillips Hilbert space. In this paper we apply this theory to relativistically covarant quantum field theoretical form of the (soluble) Lee model. We show that this theory provides a rigorous underlying basis for the Lee-Oehme-Yang-Wu construction.Comment: Plain TeX, 34 page

    Capacitance-conductance investigation on the phase transitions in Ga nanoparticles

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    We have reported on coupled capacitance-conductance measurements on Ga nanoparticles embedded in vitreous matrices. The melting of nanoparticles was clearly detected as an abrupt increase in the capacitance vs. temperature scans. The influence of the embedding matrix and of the frequency of the applied field on the dielectric response was checked. The presence of a hysteresis cycle between melting and solidification has been detected. The technique allows the identification of the various solid phases of confined Ga
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