548 research outputs found

    WWW. Euro: The Telematic Information Supply of Commercial Banks to the European Citizens

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    The debut of the new European currency certainly creates new opportunities to the citizens of the eleven involved countries. The best way to reduce the associated troubles is strictly connected to the amount of information easily available. Internet represents the most innovative and powerful medium of our age, even if it’s usage and diffusion actually cannot compete with other media. Nevertheless, it represents the best way to supply to citizens all the needed complex information, characterised by a nesting/inheriting structure. Following a qualitative schema, already tested to investigate the main usage of Internet potentialities, in this paper we verify the amount and the quality of information supplied via the virtual environment by the main actors of this historical event: the commercial banks. The goal is pursued searching for the Internet sites of the commercial banks of the eleven directly involved countries. Moreover, the sites of other European and non-European ambits are also investigated to analyse the behaviour of connected financial structures

    Supramolecular aggregates containing lipophilic Gd(III) complexes as contrast agents in MRI

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    Magnetic resonance imaging (MRI) contrast agents based on paramagnetic gadolinium complexes are widely used in biomedical research and diagnosis. Their application is intended to improve efficacy of MRI providing physiological information along with the impressive anatomical detail already obtained by images without contrast. The classical gadolinium complexes currently used for MRI contrast enhancement are all lowmolecularweightcompounds that rapidly equilibrate between the intra and extravascular spaces after intravenous administration. In order to obtain gadolinium-based agents with different pharmacokinetic properties, supramolecular aggregates such as micelles and liposomes have been recently proposed. Micelles and liposomes, obtained by the aggregation of lipophilic gadolinium complexes are here described, with the aim to correlate their structural and relaxometric properties.We report on the state of the art in the development of supramolecular aggregates obtained by self-assembly of lipophilic gadolinium complexes and aggregates in which lipophilic gadolinium complexes are assembled with surfactants. Moreover aggregates derivatized with bioactive molecules, such as peptides and antibodies, acting as target selective MRI contrast agents are described

    In vitro and in vivo evaluation of In-111-DTPAGlu-G-CCK8 for cholecystokinin-B receptor imaging

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    Regulatory peptides and their analogs are being extensively investigated as radiopharmaceuticals for cancer imaging and therapy. Receptors of the cholecystokinin family have been shown to be overexpressed in different types of neuroendocrine tumors. The purposes of this study were to evaluate the cholecystokinin octapeptide amide (CCK8) peptide tagged with a diethylenetriaminepentaacetic acid derivative (DTPAGlu) and to test whether a 111In-labeled conjugate (111In-DTPAGlu-G-CCK8, a derivative containing the chelating agent DTPAGlu bound through a glycine linker at the N-terminal end of the bioactive peptide CCK8) is suitable for cholecystokinin-B receptor (CCKBR) imaging. Methods: CCK8 was synthesized by solidphase techniques and covalently coupled to DTPAGlu through a glycine linker at its amino terminus. The compound was labeled with 111In. The radiochemical purity and stability of the compound were assessed by chromatographic methods. NIH-3T3 and A431 cells overexpressing CCKBR were used to characterize the in vitro properties of the compound. Nude mice bearing control and CCKBR-overexpressing A431 xenografts were used as an in vivo model. Results: DTPAGlu-G-CCK8 showed rapid and efficient labeling with 111In. The radiolabeled conjugate showed specific binding to both cell lines overexpressing CCKBR. Binding was saturable, with a dissociation constant of 20 nmol/L in both cell systems. Both cell lines showed internalization of the ligand after interaction with the receptor. Biodistribution studies showed rapid localization of 111In-DTPAGlu- G-CCK8 on CCKBR-overexpressing A431 xenografts that was severalfold higher than that on control tumors at all time points tested. Unbound activity showed rapid clearance of over 80% through the kidneys by 30 min after injection. The labeled peptide conjugate was very stable in serum but showed a rapid breakdown after injection. Incubation with kidney homogenates suggested that most breakdown occurred in the kidneys, favoring the clearance of unbound activity. Conclusion: Our findings indicate that the in vitro and in vivo characteristics of 111In-DTPAGlu-G-CCK8 are favorable for CCKBR imaging, as thepeptide shows high-affinity binding to the receptor, is internalized in CCKBR-expressing cells, and shows avid uptake in CCKBR-overexpressing xenografts, with rapid clearance of unbound radioactivity through the kidneys. Furthermore, the ease of synthesis, high labeling efficiency, and chemical stability of DTPAGlu make this chelating moiety an ideal candidate for widespread use in peptide radiolabeling for nuclear medicine applications

    Fast Reinforcement Learning with Large Action Sets Using Error-Correcting Output Codes for MDP Factorization

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    International audienceThe use of Reinforcement Learning in real-world scenarios is strongly limited by issues of scale. Most RL learning algorithms are unable to deal with problems composed of hundreds or sometimes even dozens of possible actions, and therefore cannot be applied to many real-world problems. We consider the RL problem in the supervised classification framework where the optimal policy is obtained through a multiclass classifier, the set of classes being the set of actions of the problem. We introduce error-correcting output codes (ECOCs) in this setting and propose two new methods for reducing complexity when using rollouts-based approaches. The first method consists in using an ECOC-based classifier as the multiclass classifier, reducing the learning complexity from O(A2) to O(Alog(A)) . We then propose a novel method that profits from the ECOC's coding dictionary to split the initial MDP into O(log(A)) separate two-action MDPs. This second method reduces learning complexity even further, from O(A2) to O(log(A)) , thus rendering problems with large action sets tractable. We finish by experimentally demonstrating the advantages of our approach on a set of benchmark problems, both in speed and performance

    Ruthenium(III) complexes entrapped in liposomes with enhanced cytotoxic and anti-metastatic properties

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    Metal-based anticancer drugs are pivotal in the fight against cancer pathologies. Since 1978 cis-platin was licensed for medical treatment of a wide number of tumor pathologies(1). However its chemiotherapic use is strongly limited by many and severe side effects and acquired tumor resistance. Since these limitations could be overcome by other metal complexes, in the last thirty years ruthenium compounds have been tested showing a remarkable antitumoral and antimetastatic activity associated with a lower toxicity. A hexacoordinate Ru(III) complex (NAMI-A) is currently undergoing advanced clinical evaluation (2). All data indicate that NAMI-A acts as a pro-drug, but the integrity of ruthenium complexes is essential to store the cytotoxic activity. In this scenario the condition of administration of ruthenium drugs are crucial to exploit their anticancer activity (3). In the last years innovative strategies have been produced to vehicle ruthenium ions in tumor cells like aggregates. This study aims to incorporate the ruthenium complexes in the inner aqueous compartment of liposomes and to test biological properties of two NAMI-A like pyridine derivatives. Specifically, we have investigated the pyridine derivatives of the sodium-compensated analogue of NAMI-A, Na[trans-RuCl4(pyridine)(DMSO)] (NAMI-Pyr) and Na[trans-RuCl4(Pytri)(DMSO)] (NAMI-Pytri). In thelatter complex the pyridine ligand is functionalized with a sugar moiety so as to increase biocompatibility and the ability to cross the cell membrane. The stability of the complexes was studied and compared in solution at different pH following UV-VIS spectra. Lipid formulations based on Egg PC were prepared adding Cholesterol, DSPE-PEG2000 joining molar ratio 57/38 /5% w/w respectively in MeOH/CHCl3 (50/50 v/v) mixture and hydrated with 0.9% w/w of NaCl. This composition was selected to reproduce analog supramolecular aggregates in clinical use to vehicle doxorubicin (Doxil). Ruthenium complexes were loaded into liposomes using the passive equilibration loading method. Full drug containing liposomes were structurally characterized by dynamic light scattering (DLS) measurements. Data indicate the formation of stable aggregates with size and shape in the right range for in vivo applications. The amount of encapsulated ruthenium complexes was quantified by means of ICP-AES. Stability and drug release properties of ruthenium containing liposomes were confirmed in buffer. The growth inhibitory effects of both liposomal and free complexes drug were tested on prostate cancer cells (PC3). Preliminary results show high cytotoxic effect of ruthenium complexes delivered by supramolecular aggregates with respect to free complexes drug

    Grain boundary motion in layered phases

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    We study the motion of a grain boundary that separates two sets of mutually perpendicular rolls in Rayleigh-B\'enard convection above onset. The problem is treated either analytically from the corresponding amplitude equations, or numerically by solving the Swift-Hohenberg equation. We find that if the rolls are curved by a slow transversal modulation, a net translation of the boundary follows. We show analytically that although this motion is a nonlinear effect, it occurs in a time scale much shorter than that of the linear relaxation of the curved rolls. The total distance traveled by the boundary scales as ϵ1/2\epsilon^{-1/2}, where ϵ\epsilon is the reduced Rayleigh number. We obtain analytical expressions for the relaxation rate of the modulation and for the time dependent traveling velocity of the boundary, and especially their dependence on wavenumber. The results agree well with direct numerical solutions of the Swift-Hohenberg equation. We finally discuss the implications of our results on the coarsening rate of an ensemble of differently oriented domains in which grain boundary motion through curved rolls is the dominant coarsening mechanism.Comment: 16 pages, 5 figure

    Physicochemical properties of mixed micellar aggregates containing CCK peptides and Gd complexes designed as tumor specific contrast agents in MRI

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    New amphiphilic molecules containing a bioactive peptide or a claw moiety have been prepared in order to obtain mixed micelles as target-specific contrast agents in magnetic resonance imaging. The first molecule, C18H37CONH(AdOO)2-G-CCK8 (C18CCK8), contains a C18 hydrophobic moiety bound to the C-terminal cholecystokinin octapeptide amide (CCK 26-33 or CCK8). The second amphiphilic compound, C18H37CONHLys(DTPAGlu)CONH2 (C18DTPAGlu) or its gadolinium complex, (C18DTPAGlu- (Gd)), contains the same C18 hydrophobic moiety bound, through a lysine residue, to the DTPAGlu chelating agent. The mixed aggregates as well as the pure C18DTPAGlu aggregate, in the presence and absence of Gd, have been fully characterized by surface tension measurements, FT-PGSE-NMR, fluorescence quenching, and small-angle neutron scattering measurements. The structural characterization of the mixed aggregates C18DTPAGlu(Gd)-C18CCK8 indicates a spherical arrangement of the micelles with an external shell of 21 Å and an inner core of 20 Å. Both the DTPAGlu(Gd) complexes and the CCK8 peptides point toward the external surface. The measured values for relaxivity in saline medium at 20 MHz proton Larmor frequency and 25 °C are 18.7 mM-1 s-1. These values show a large enhancement in comparison with the isolated DTPAGlu(Gd) complex
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