45,054 research outputs found
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
Evidence for the decay B0→J/ψω and measurement of the relative branching fractions of meson decays to J/ψη and J/ψη′
First evidence of the B 0 → J / ψ ω decay is found and the B s 0 → J / ψ η and B s 0 → J / ψ η ′ decays are studied using a dataset corresponding to an integrated luminosity of 1.0 fb -1 collected by the LHCb experiment in proton-proton collisions at a centre-of-mass energy of sqrt(s) = 7 TeV. The branching fractions of these decays are measured relative to that of the B 0 → J / ψ ρ 0 decay:frac(B (B 0 → J / ψ ω), B (B 0 → J / ψ ρ 0)) = 0.89 ± 0.19 (stat) - 0.13 + 0.07 (syst),frac(B (B s 0 → J / ψ η), B (B 0 → J / ψ ρ 0)) = 14.0 ± 1.2 (stat) - 1.5 + 1.1 (syst) - 1.0 + 1.1 (frac(f d, f s)),frac(B (B s 0 → J / ψ η ′), B (B 0 → J / ψ ρ 0)) = 12.7 ± 1.1 (stat) - 1.3 + 0.5 (syst) - 0.9 + 1.0 (frac(f d, f s)), where the last uncertainty is due to the knowledge of f d / f s, the ratio of b-quark hadronization factors that accounts for the different production rate of B 0 and B s 0 mesons. The ratio of the branching fractions of B s 0 → J / ψ η ′ and B s 0 → J / ψ η decays is measured to befrac(B (B s 0 → J / ψ η ′), B (B s 0 → J / ψ η)) = 0.90 ± 0.09 (stat) - 0.02 + 0.06 (syst)
Going Beyond Counting First Authors in Author Co-citation Analysis
The present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Measurement of the B0–B0 oscillation frequency Δmd with the decays B0→D−π+ and B0→ J/ψK∗0
The B
0
–B
0
oscillation frequency Δmd is measured by the LHCb experiment using a dataset corresponding
to an integrated luminosity of 1.0 fb−1
of proton–proton collisions at √
s = 7 TeV, and is found to be
Δmd
=0.5156±0.0051 (stat.)±0.0033 (syst.) ps−1
. The measurement is based on results from analyses
of the decays B
0
→ D
−π
+ (D
−
→ K
+π
−π
−) and B
0
→ J/ψK
∗0
(J/ψ →μ
+μ
−,K
∗0
→ K
+π
−) and
their charge conjugated modes
Measurement of the ratio of branching fractions B(B0→K∗0γ )/B(B0s→φγ ) and the directCP asymmetry inB 0→K∗0γ
The ratio of branching fractions of the radiative B decays B0→K⁎0γ and B0s→ϕγ has been measured using an integrated luminosity of 1.0 fb−1 of pp collision data collected by the LHCb experiment at a centre-of-mass energy of s√=7TeV. The value obtained is
B(B0→K⁎0γ)B(B0s→ϕγ)=1.23±0.06(stat.)±0.04(syst.)±0.10(fs/fd),
where the first uncertainty is statistical, the second is the experimental systematic uncertainty and the third is associated with the ratio of fragmentation fractions fs/fd. Using the world average value for B(B0→K⁎0γ), the branching fraction B(B0s→ϕγ) is measured to be (3.5±0.4)×10−5.
The direct CP asymmetry in B0→K⁎0γ decays has also been measured with the same data and found to be
ACP(B0→K⁎0γ)=(0.8±1.7(stat.)±0.9(syst.))%.
Both measurements are the most precise to date and are in agreement with the previous experimental results and theoretical expectations
Measurement of CP observables in B-+/- -> D(*)K-+/- and B-+/- -> D(*)pi(+/-) decays
Measurements of CP observables in B-+/- -> D(*)K-+/- and B-+/- -> D(*)pi(+/-) decays are presented, where D(*) indicates a neutral Dor D* meson that is an admixture of D(*)(0) and (D) over bar(*)(0) states. Decays of the D* meson to the D pi(0)and D gamma final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the Bcandidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K-+/-pi(-/+), K+K- and pi(+)pi(-) final states. The analysis uses a sample of charged Bmesons produced in ppcollisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0fb- 1taken at centre- of- mass energies of root s = 7, 8 and 13 TeV, respectively. The study of B-perpendicular to -> D*K-perpendicular to and B-perpendicular to -> D*pi(perpendicular to) decays using a partial reconstruction method is the first of its kind, while the measurement of B-+/- -> DK +/- and B-+/- -> D pi(+/-) decays is an update of previous LHCb measurements. The B-+/- -> DK +/- results are the most precise to date. (c) 2017 The Author. Published by Elsevier B. V
Dispelling the Myths Behind First-author Citation Counts
We conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
The pixel module for the Inner Tracking System upgrade of ALICE at LHC
The ALICE (A Large Ion Collider Experiment) detector at the CERN LHC collider was designed to address
the physics of strongly interacting matter, and in particular the properties of the Quark-Gluon
Plasma (QGP) using proton-proton, proton-nucleus, and nucleus-nucleus collisions. Even if with
this physics goal a lot of important results were already reached, there are still several fundamental
measurements to be finalized, like high precision measurements of rare probes (D, B mesons and
Lambda barions decays) over a broad range of transverse momenta. In order to achieve these new
results, a wide upgrade plan was approved that combined with a significant increase of luminosity
will enhance the ALICE physics capabilities enormously.
The ALICE Inner Tracking System (ITS) upgrade is one of the major improvements of the experimental
set-up that will take place in 2019-2020 where the whole ITS sub-detector will be replaced with
a new one realized using a innovative CMOS Monolithic Active Pixel silicon Sensor (MAPS), called
ALPIDE. This new upgraded ITS will be realized using more than twenty-four thousand ALPIDE
chips organized in seven different cylindrical layers surrounding the ALICE interaction point along
the beam-line, for a total surface of about ten square meters. The main features of the future ALICE
ITS are a low material budget, high granularity and low power consumption. All these peculiar capabilities
will allow for full reconstruction of rare heavy flavor decays and the achievement of the
physics goals.
In this talk after a description of new ALIPIDE pixel chip and the whole ITS upgrade project, will be
presented the construction procedure of the basic building block of the detector, namely the module,
and the laboratory characterization of this element
Branching fraction and CP asymmetry of the decays B+→K0Sπ+ and B+→K0SK+
An analysis of B+ → K0
Sπ+ and B+ → K0
S K+ decays is performed with the LHCb experiment. The pp
collision data used correspond to integrated luminosities of 1 fb−1 and 2 fb−1 collected at centre-ofmass
energies of
√
s = 7 TeV and
√
s = 8 TeV, respectively. The ratio of branching fractions and the
direct CP asymmetries are measured to be B(B+ → K0
S K+
)/B(B+ → K0
Sπ+
) = 0.064 ± 0.009 (stat.) ±
0.004 (syst.), ACP(B+ → K0
Sπ+
) = −0.022 ± 0.025 (stat.) ± 0.010 (syst.) and ACP(B+ → K0
S K+
) =
−0.21 ± 0.14 (stat.) ± 0.01 (syst.). The data sample taken at
√
s = 7 TeV is used to search for
B+
c
→ K0
S K+ decays and results in the upper limit ( fc · B(B+
c
→ K0
S K+
))/( fu · B(B+ → K0
Sπ+
)) <
5.8 × 10−2 at 90% confidence level, where fc and fu denote the hadronisation fractions of a ¯b
quark
into a B+
c or a B+ meson, respectively
Measurement of the D+/- production asymmetry in 7 TeV pp collisions
The asymmetry in the production cross-section \sigma of D+/- mesons, A_P = (\sigma(D+) - \sigma(D-))/(\sigma(D+) + \sigma(D-)), is measured in bins of pseudorapidity \eta and transverse momentum p_T within the acceptance of the LHCb detector. The result is obtained with a sample of D+ -> K_S pi+ decays corresponding to an integrated luminosity of 1.0 fb^-1, collected in pp collisions at a centre of mass energy of 7 TeV at the Large Hadron Collider. When integrated over the kinematic range 2.0 K_S pi+ decay is negligible. No significant dependence on \eta or p_T is observed
- …
