On the propagation of a perturbation in an anharmonic system

We give a not trivial upper bound on the velocity of disturbances in an infinitely extended anharmonic system at thermal equilibrium. The proof is achieved by combining a control on the non equilibrium dynamics with an explicit use of the state invariance with respect to the time evolution.Comment: 14 page

Pharmacological and neurobiological studies on Neuropeptide S and its receptor

Neuropeptide S (NPS) is the last neuropeptide identified via reverse pharmacology techniques. NPS selectively binds and activates a previously orphan GPCR, now named NPSR, producing intracellular Ca2+ mobilization and stimulation of cAMP levels. Biological functions modulated by the NPS/NPSR system include anxiety, arousal, locomotion, food intake, learning and memory, pain and drug addiction. In our laboratories we provided further evidence that NPS injected supraspinally in mice acts as a stimulatory anxiolytic. In fact, in the mouse righting reflex (RR) test, NPS (0.01- 1 nmol, i.c.v.) was able to reduce in a dose dependent manner the percent of animals losing the RR in response to diazepam (15mg/kg, i.p.) and their sleep time. Furthermore, NPS in the same range of doses caused a significant increase in locomotor activity (LA) in mice. These effects were associated with a clear anxiolytic-like action elicited by NPS in the mouse elevated plus maze (EPM) test, open field (OF) test and stress-induced hyperthermia (SIH) assay. Thus NPS evokes an unique pattern of behavioural effects: stimulation associated with anxiolysis. To deeply investigate the biological roles played by the NPS/NPSR system the development of pharmacological (i.e. selective NPSR ligands, particularly antagonists) and genetic (i.e. receptor knockout animals) tools are needed. In collaboration with the medicinal chemistry group of the University of Ferrara, we performed a series of classical structure-activity (SAR) studies on NPS sequence. Specifically, NPS positions 2, 3, 4 and 5 were investigated in details, since they were demonstrated to be crucial for NPS bioactivity. Studies focussed on NPS position 5 led to the identification and the in vitro and in vivo pharmacological characterization of the first generation of NPSR peptide antagonists. In vitro, in HEK293 cells stably expressing the mouse NPSR, [D-Cys(tBu)5]NPS up to 100 μM did not stimulate Ca2+ mobilization but was able to counteract in a competitive manner the stimulatory action of NPS (pA2: 6.44). In vivo, in the RR test, [D-Cys(tBu)5]NPS at 10 nmol was inactive per se but dose dependently antagonized the arousal-promoting action of NPS 0.1 nmol. [D-Val5]NPS acted in vitro as a pure NPSR antagonist, with a pKB of 6.54 in inhibition experiments. In vivo, in LA test, [D-Val5]NPS at 10 nmol completely blocked the stimulatory effect evoked by NPS. In a further medicinal chemistry study, the potent NPSR antagonist [tBu-D-Gly5]NPS was identified. In vitro, [tBu-D-Gly5]NPS did not stimulate calcium mobilization but blocked the stimulant action of NPS with a pKB of 7.06 7. In vivo, in RR assay, [tBu-D-Gly5]NPS (0.1-10 nmol, i.c.v.) was inactive per se but dose dependently antagonized the arousal-promoting action of NPS 0.1 nmol. Similarly in the LA assay [tBu-D-Gly5]NPS (0.1-10 nmol, i.c.v.) was inactive per se but was able to counteract the stimulatory effect evoked by 0.1 nmol NPS in a dose dependent manner. SHA 68 has been previously identified as the first non peptide NPSR antagonist. In our laboratories we further assessed the pharmacological profile of SHA 68 in vitro and in vivo. In vitro SHA 68 was inactive per se up to 10 μM while it antagonized NPSstimulated Ca2+ mobilization in a competitive manner showing a pA2 value of 8.06. In vivo, in the mouse RR assay, SHA68 50 mg/kg i.p. fully prevented the arousal promoting action of NPS 0.1 nmol. In LA experiments, SHA 68 50 mg/kg i.p. was able to partially counteract the stimulant effects elicited by NPS 0.1 nmol. Instead, the anxiolytic-like effects of NPS 0.1 nmol in mouse OF test were slightly reduced by SHA 68. Collectively these data demonstrated the exclusive involvement of NPSR in the arousal promoting and locomotor stimulant effects of NPS. Finally, we backcrossed on the CD-1 strain the NPSR knockout mice originally generated on the 129Sv/Ev genetic background. A first phenotype analysis revealed no locomotor differences between NPSR(+/+) and NPSR(-/-) mice, with the exception of rearing behaviour that was reduced in knockout animals. Furthermore, the behaviour of NPSR(+/+) and NPSR(-/-) mice in the EPM, OF and SIH tests is superimposable. Similarly no differences were detected in the novel object recognition, forced swimming, RR and formalin assays. However, the stimulant actions of 1 nmol NPS in RR and in LA test could be detected in NPSR(+/+) but not in NPSR(-/-) mice. Collectively these data demonstrated that endogenous NPS/NPSR system does not play a role in the control of locomotion, anxiety, depression and memory, at least under the present experimental conditions. These results demonstrated that the NPS stimulant effects are selectively due to NPSR activation, corroborating the findings obtained with NPSR antagonists. In conclusion, the research activity performed during the PhD program led to the identification of the first generation of NPSR peptide antagonists. The use of these research tools in parallel with knockout studies generated converging evidence on the biological effects induced by the selective activation of NPSR

Jacobi beta ensemble and b-Hurwitz numbers

We express correlators of the Jacobi beta ensemble in terms of (a special case of) b-Hurwitz numbers, a deformation of Hurwitz numbers recently introduced by Chapuy and Do{\l}\k{e}ga. The proof relies on a generalized Selberg integral. The Laguerre limit is also considered. All the relevant b-Hurwitz numbers are interpreted (following Bonzom, Chapuy, and Do{\l}\k{e}ga) in terms of colored monotone Hurwitz maps.Comment: 15 pages, 1 figur

Tau functions: theory and applications to matrix models and enumerative geometry

In this thesis we study partition functions given by matrix integrals from the point of view of isomon- odromic deformations, or more generally of Riemann\u2013Hilbert problems depending on parameters

The Ideology of New Public Management, Associational Representation and the Global Financial Crisis

This paper argues that the 2008 financial crisis accelerated a set of long-term dynamics which in turn have undermined two dominant models of state-society relations. On the one hand, the paper examines how the concept of social citizenship is based on a vision of state-society relations, which in recent years has been oriented by a philosophy of marketization of the state and of the relation between citizens and the state. On the other hand, it discusses an emerging emphasis on the role of organised civil society as a different and competing approach to state-society relations. Discussion will centre on how the interactions between these two ideologies and the related practices have impacted on conceptions of the modern state. Among the factors that affect this interaction are the impact of migration, the erosion of welfare states, and the redefined character of social vulnerability which now affect new groups of individuals. The paper considers all these changes as background phenomena which impact on relations between state and society in several ways, but particularly in terms of the meaning of social citizenshi

Blockchain for supply chain traceability and anticounterfeiting: the oracles’ enabling role

Blockchain and physical oracles in the Collectible Industry. Supply chain fairness and bargaining power in agriculture supply chain: the blockchain effect. Unlocking the Blockchain Potentials through Oracles: Empirical Evidences on Supply Chain Challenges and Performance

Numerical studies to detect chaotic motion in the full planar averaged three-body problem

In this paper, the author deals with a well-known problem of Celestial Mechanics, namely the three-body problem. A numerical analysis has been done in order to prove existence of chaotic motions of the full-averaged problem in particular configurations. Full because all the three bodies have non-negligible masses and averaged because the Hamiltonian describing the system has been averaged with respect to a fast angle. A reduction of degrees of freedom and of the phase-space is performed in order to apply the notion of covering relations and symbolic dynamics