2,993 research outputs found
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 ÎĽM 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 ÎĽM 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
Bessel kernel determinants and integrable equations
We derive differential equations for multiplicative statistics of the Bessel
determinantal point process depending on two parameters. In particular, we
prove that such statistics are solutions to an integrable nonlinear partial
differential equation describing isospectral deformations of a Sturm--Liouville
equation. We also derive identities relating solutions to the integrable
partial differential equation and to the Sturm--Liouville equation which imply
an analogue for Painlev\'e V of Amir--Corwin--Quastel ``integro-differential
Painlev\'e II equation''. This equation reduces, in a degenerate limit, to the
system of coupled Painlev\'e V equations derived by Charlier and Doeraene for
the generating function of the Bessel process, and to the Painlev\'e V equation
derived by Tracy and Widom for the gap probability of the Bessel process.
Finally, we study an initial value problem for the integrable partial
differential equation. The approach is based on Its--Izergin--Korepin--Slavnov
theory of integrable operators and their associated Riemann--Hilbert problems.Comment: 22 page
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
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