4,637 research outputs found
Biosynthesis of H2S is impaired in non-obese diabetic (NOD) mice
Hydrogen sulphide (H2S) has been involved in cardiovascular homoeostasis but data about its role in animal models of diabetic pathology are still lacking. Here, we have analysed H2S signalling in a genetic model of diabetes, the non-obese diabetic (NOD) mice.
NOD mice exhibit a progressive endothelial dysfunction characterized by a reduced reactivity of blood vessels as diabetes develops. NOD mice were divided into three groups according to different glycosuria values: NOD I, NOD II and NOD III. Age-matched non-obese resistant (NOR) mice were used as controls. H(2)S levels in plasma and aortic tissue were measured. Functional studies in aorta were carried out in isolated organ baths using both an exogenous source of H2S (NaHS) and the metabolic precursor (L-cysteine). Real time PCR and western blot analysis were also carried out on aortic tissues.
NOD mice exhibited a progressive reduction of H2S plasma levels, which paralleled disease severity. L-cysteine-induced H2S production by aortic tissues was also progressively reduced. L-cysteine-induced vasorelaxation was significantly reduced in NOD mice while NaHS-induced relaxation was unaffected. ODQ (guanylate cyclase inhibitor), L-NAME (NO synthase inhibitor) or PAG, an inhibitor of cystathionine-gamma-lyase (CSE) inhibited H2S production induced by L-cysteine.
In NOD mice, endogenous H2S production is significantly impaired. Also, the ability of isolated aorta to respond to exogenous H2S is enhanced and endothelium-derived NO appears to be involved in the enzymatic conversion of L-cysteine into H2S
Sphingosine-1-phosphate modulates vascular permeability and cell recruitment inacute inflammation in vivo.
The sphingosine kinase (SPK)/sphingosine-1-phosphate (S1P) pathway recently has been associated with a variety of inflammatory-based diseases. The majority of these studies have been performed in vitro. Here, we have addressed the relevance of the SPK/S1P pathway in the acute inflammatory response in vivo by using different well known preclinical animal models. The study has been performed by operating a pharmacological modulation using 1) L-cycloserine and DL-threo-dihydrosphingosine (DTD), S1P synthesis inhibitors or 2) 2-undecyl-thiazolidine-4-carboxylic acid (BML-241) and N-(2,6-dichloro-4-pyridinyl)-2-[1,3-dimethyl-4-(1-methylethyl)-1H-pyrazolo[3,4-b]pyridin-6-yl]-hydrazinecarboxamide (JTE-013), specific S1P(2) and S1P(3) receptor antagonists. After local injection of carrageenan in mouse paw S1P release significantly increases locally and decreases during the resolution phase. Expression of SPKs and S1P(2) and S1P(3) receptors is increased in inflamed tissues. Administration of L-cycloserine or DTD caused a significant anti-inflammatory effect. By using different animal models we have also demonstrated that the SPK/S1P pathway contributes to changes in vascular permeability and promotes cell recruitment. The S1P effect on cell recruitment results is receptor-mediated because both JTE-013 and BML-241 inhibited zymosan-induced cell chemotaxis without effect on vascular leakage. Conversely, changes in vascular permeability involve mainly SPK activity, because compound 48/80-induced vascular leakage was significantly inhibited by DTD. In conclusion, the SPK/S1P pathway is involved in acute inflammation and could represent a valuable therapeutic target for developing a new class of anti-inflammatory drugs
Persistent storage of non-event data in the CMS databases
In the CMS experiment, the non event data needed to set up the detector, or being produced by it, and needed to calibrate the physical responses of the detector itself are stored in ORACLE databases. The large amount of data to be stored, the number of clients involved and the performance requirements make the database system an essential service for the experiment to run. This note describes the CMS condition database architecture, the data-flow and PopCon, the tool built in order to populate the offline databases. Finally, the first results obtained during the 2008 and 2009 cosmic data taking are presented.In the CMS experiment, the non event data needed to set up the detector, or being produced by it, and needed to calibrate the physical responses of the detector itself are stored in ORACLE databases. The large amount of data to be stored, the number of clients involved and the performance requirements make the database system an essential service for the experiment to run. This note describes the CMS condition database architecture, the data-flow and PopCon, the tool built in order to populate the offline databases. Finally, the first experience obtained during the 2008 and 2009 cosmic data taking are presented
Design of vaccine efficacy trials during public health emergencies
Public Health Emergencies (PHEs) provide a complex and challenging environment for vaccine evaluation. Under the R&D Blueprint Plan of Action, the World Health Organization (WHO) has convened a group of experts to agree on standard procedures to rapidly evaluate experimental vaccines during PHEs while maintaining the highest scientific and ethical standards. The Blueprint priority diseases, selected for their likelihood to cause PHEs and the lack of adequate medical countermeasures,were used to frame our methodological discussions. Here, we outline major vaccine study designs to be used in PHEs and summarize high-level recommendations for their use in this setting. We recognize that the epidemiology and transmission dynamics of the Blueprint priority diseasesmay be highly uncertain and that the unique characteristics of the vaccines and outbreak settings may affect our study design. To address these challenges, our group underscores the need for novel, flexible,and responsive trial designs. We conclude that assignment to study groups using randomization is a key principle underlying rigorous study design and should be utilized except in exceptional circumstances. Advance planning for vaccine trial designs is critical for rapid and effective response to a PHE and to advance knowledge to address and mitigate future PHEs
INFN What Next: Ultra-relativistic Heavy-Ion Collisions
This document was prepared by the community that is active in Italy, within
INFN (Istituto Nazionale di Fisica Nucleare), in the field of
ultra-relativistic heavy-ion collisions. The experimental study of the phase
diagram of strongly-interacting matter and of the Quark-Gluon Plasma (QGP)
deconfined state will proceed, in the next 10-15 years, along two directions:
the high-energy regime at RHIC and at the LHC, and the low-energy regime at
FAIR, NICA, SPS and RHIC. The Italian community is strongly involved in the
present and future programme of the ALICE experiment, the upgrade of which will
open, in the 2020s, a new phase of high-precision characterisation of the QGP
properties at the LHC. As a complement of this main activity, there is a
growing interest in a possible future experiment at the SPS, which would target
the search for the onset of deconfinement using dimuon measurements. On a
longer timescale, the community looks with interest at the ongoing studies and
discussions on a possible fixed-target programme using the LHC ion beams and on
the Future Circular Collider.Comment: 99 pages, 56 figure
New Eco-gas mixtures for the Extreme Energy Events MRPCs: results and plans
The Extreme Energy Events observatory is an extended muon telescope array,
covering more than 10 degrees both in latitude and longitude. Its 59 muon
telescopes are equipped with tracking detectors based on Multigap Resistive
Plate Chamber technology with time resolution of the order of a few hundred
picoseconds. The recent restrictions on greenhouse gases demand studies for new
gas mixtures in compliance with the relative requirements. Tetrafluoropropene
is one of the candidates for tetrafluoroethane substitution, since it is
characterized by a Global Warming Power around 300 times lower than the gas
mixtures used up to now. Several mixtures have been tested, measuring
efficiency curves, charge distributions, streamer fractions and time
resolutions. Results are presented for the whole set of mixtures and operating
conditions, %. A set of tests on a real EEE telescope, with cosmic muons, are
being performed at the CERN-01 EEE telescope. The tests are focusing on
identifying a mixture with good performance at the low rates typical of an EEE
telescope.Comment: 8 pages, 6 figures, proceedings for the "XIV Workshop on Resistive
Plate Chambers and Related Detectors" (19-23 February 2018), Puerto Vallarta,
Jalisco State, Mexic
The Extreme Energy Events HECR array: status and perspectives
The Extreme Energy Events Project is a synchronous sparse array of 52
tracking detectors for studying High Energy Cosmic Rays (HECR) and Cosmic
Rays-related phenomena. The observatory is also meant to address Long Distance
Correlation (LDC) phenomena: the network is deployed over a broad area covering
10 degrees in latitude and 11 in longitude. An overview of a set of preliminary
results is given, extending from the study of local muon flux dependance on
solar activity to the investigation of the upward-going component of muon flux
traversing the EEE stations; from the search for anisotropies at the sub-TeV
scale to the hints for observations of km-scale Extensive Air Shower (EAS).Comment: XXV ECRS 2016 Proceedings - eConf C16-09-04.
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
Centrality dependence of charged particle production at large transverse momentum in Pb-Pb collisions at TeV
The inclusive transverse momentum () distributions of primary
charged particles are measured in the pseudo-rapidity range as a
function of event centrality in Pb-Pb collisions at
TeV with ALICE at the LHC. The data are presented in the range
GeV/ for nine centrality intervals from 70-80% to 0-5%.
The Pb-Pb spectra are presented in terms of the nuclear modification factor
using a pp reference spectrum measured at the same collision
energy. We observe that the suppression of high- particles strongly
depends on event centrality. In central collisions (0-5%) the yield is most
suppressed with at -7 GeV/. Above
GeV/, there is a significant rise in the nuclear modification
factor, which reaches for GeV/. In
peripheral collisions (70-80%), the suppression is weaker with almost independently of . The measured nuclear
modification factors are compared to other measurements and model calculations.Comment: 17 pages, 4 captioned figures, 2 tables, authors from page 12,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/284
Charge separation relative to the reaction plane in Pb-Pb collisions at TeV
Measurements of charge dependent azimuthal correlations with the ALICE
detector at the LHC are reported for Pb-Pb collisions at TeV. Two- and three-particle charge-dependent azimuthal correlations in
the pseudo-rapidity range are presented as a function of the
collision centrality, particle separation in pseudo-rapidity, and transverse
momentum. A clear signal compatible with a charge-dependent separation relative
to the reaction plane is observed, which shows little or no collision energy
dependence when compared to measurements at RHIC energies. This provides a new
insight for understanding the nature of the charge dependent azimuthal
correlations observed at RHIC and LHC energies.Comment: 12 pages, 3 captioned figures, authors from page 2 to 6, published
version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/286
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