Edaravone Inhibits Protein Carbonylation by a Direct Carbonyl-Scavenging Mechanism: Focus on Reactivity, Selectivity, and Reaction Mechanisms

The aim of this study was to evaluate the ability of the well-known radical scavenging compound edaravone (EDA) to entrap and detoxify reactive carbonyl species (RCS) derived from lipid peroxidation [4-hydroxy-trans-2-nonenal (HNE), acrolein and glyoxal], as well as its ability to prevent RCS-induced protein carbonylation, by using hemoglobin (Hb) modified by HNE as an in vitro model. Through a combined HPLC and high-resolution mass spectrometric approach, we confirmed the ability of EDA to scavenge precursors for either advanced glycation or lipoxidation end products (EAGLEs), such as glyoxal, and demonstrated for the first time that EDA is also a potent quencher of \u3b1,\u3b2-unsaturated aldehydes (providing mass spectral characterization of the adducts), being significantly more active than a series of well-known RCS sequestering agents. Direct infusion analysis of the intact protein and nano LC-ESI-MS/MS analysis of the tryptic digest, carried out on an LTQ-Orbitrap hybrid mass spectrometer, were used to study the modifications occurring on Hb after exposure to increasing HNE concentrations, providing evidence for Cys93 (Hb \u3b2-chain) involvement in covalent attachment, and to demonstrate the ability of EDA dose-dependently to inhibit Hb carbonylation. Computational studies allowed us to elucidate the mechanism of EDA-RCS interaction and to explain the preferential site of HNE adduction to Hb. The same combined approach indicated that EDA is not a selective RCS scavenger, being able to react also with nontoxic, physiologically relevant aldehydes, such as pyridoxa

The EEE MRPC telescopes as tracking tools to monitor building stability with cosmic muons

This paper discusses the possibility to employ the Multi-gap Resistive Plate Chambers (MRPC) of the Extreme Energy Events (EEE) Project as muon tracking detectors to monitor the long term stability of civil buildings and structures when used in conjunction with additional detectors, to reconstruct the average direction of the cosmic muon tracks passing through both devices and any small variation over long time acquisition periods. The performance of such setup is discussed and preliminary experimental coincidence results obtained with a 40 7 60 cm2scintillator detector operated in the same building with one of the EEE telescopes, at about 15 m vertical distance from it, are presented. Simple Monte Carlo and GEANT simulations were also carried out to evaluate typical acceptance values for the operating conditions employed so far, to extrapolate to other geometrical configurations, and to evaluate multiple scattering effects

Looking at the sub-TeV sky with cosmic muons detected in the EEE MRPC telescopes

Distributions of secondary cosmic muons were measured by the Multigap Resistive Plate Chambers (MRPC) telescopes of the Extreme Energy Events (EEE) Project, spanning a large angular and temporal acceptance through its sparse sites, to test the possibility to search for any anomaly over long runs. After correcting for the time exposure and geometrical acceptance of the telescopes, data were transformed into equatorial coordinates, and equatorial sky maps were obtained from different sites on a preliminary dataset of 110M events in the energy range at sub-TeV scale

A Multigap Resistive Plate Chambers array for the Extreme Energy Events Project

The Extreme Energy Events (EEE) Project is a Centro Fermi - CERN - INFN - MIUR Collaboration Project, for the study of extremely high-energy cosmic rays, which exploits the Multigap Resistive Plate Chamber (MRPC) technology. The excellent time resolution and good tracking capability of this detector allows us to study Extensive Air Showers (EAS) with an array of telescopes distributed all over the Italian territory. Each telescope is installed in a High School, with the additional goal to introduce students to particle and astroparticle Physics. The EEE array is composed, so far, of 47 telescopes, each made of three MRPC planes, spanning more than 10 degrees in latitude and 11 in longitude, organized in clusters and single telescope stations. The status of the experiment and the results, obtained during two recent coordinated data taking periods, will be reported. The observation of Forbush decreases, coincidence events among different telescopes and the muon decay, using more than 5 billion tracks collected in the last few months, are of particular interest

Recent results and performance of the multi-gap resistive plate chambers network for the EEE Project

The Extreme Energy Events (EEE) Project is devoted to the study of Extensive Atmospheric Showers through a network of muon telescopes, installed in High Schools, with the further aim of introducing young students to particle and astroparticle physics. Each telescope is a tracking detector composed of three Multi-gap Resistive Plate Chambers (MRPC) with an active area of 1.60 × 0.80 m(2). Their characteristics are similar to the ones built for the Time Of Flight array of the ALICE Experimentat LHC . The EEE Project started with a few pilot towns, where the telescopes have been taking data since 2008, and it has been constantly extended, reaching at present more than 50 MRPCs telescopes. They are spread across Italy with two additional stations at CERN, covering an area of around 3 × 10(5) km(2), with a total surface area for all the MRPCs of 190 m(2). A comprehensive description of the MRPCs network is reported here: efficiency, time and spatial resolution measured using cosmic rays hitting the telescopes. The most recent results on the detector and physics performance from a series of coordinated data acquisition periods are also presented

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 Potential 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, focusing on identifying a mixture with good performance at the low rates typical of an EEE telescope.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

The Extreme Energy Events experiment: An overview of the telescopes performance

The muon telescopes of the Extreme Energy Events (EEE) experiment are based on Multigap Resistive Plate Chambers (MRPC). The EEE network is composed, so far, of 53 telescopes, each made of three MRPC detectors; it is organized in clusters and single telescope stations distributed all over the Italian territory and installed in High Schools, covering an area larger than 3 7105 km2. The study of Extensive Air Showers (EAS), that is one of the goal of the project, requires excellent performance in terms of time and spatial resolution, efficiency, tracking capability and long term stability. The data from two recent coordinated data taking periods, named Run 2 and Run 3, have been used to measure these quantities and the results are here reported, together with a comparison with expectations and with the results from a beam test performed in 2006 at CERN

Search for coincident air showers over large scale distances with the EEE network

The existence of time correlations in detectors separated by distances much larger than the size of the highest energy extensive air showers (EAS) has been long discussed over the years. Several mechanisms have been proposed to justify the existence of such events and, in the last decade, some experiments have also tried to search for correlations on a large scale distance, beyond one hundred kilometers. The approaches were based on the construction of clusters of detectors placed at large relative distances, with the capability of selecting extensive air showers. Within this context, the Extreme Energy Events (EEE) experiment can provide new inputs in the search for long distance correlations, thanks to its sparse array of muon telescopes spanning all the Italian territory. The EEE telescopes are taking data since more than 10 years and enough statistics has been already accumulated to be able to search for such events, whose observation is intrinsically difficult due to the very low rates expected, many order of magnitudes smaller than the overall cosmic ray flux. In order to reduce the accidental correlations, different analysis approaches have been investigated for the selection of EAS events with the EEE telescopes. In this paper we will present preliminary results obtained by analyzing a large fraction of the statistics currently available

Test of new eco-gas mixtures for the multigap resistive plate chambers of the EEE project

The Extreme Energy Events (EEE) experiment is a project by Centro Fermi (Museo Storico della Fisica e Centro Studi e Ricerche \u201cEnrico Fermi\u201d) in collaboration with INFN, CERN and MIUR, designed to study cosmic rays via a network of muon telescopes, based on the Multigap Resistive Plate Chambers (MRPC) technology. Due to its wide coverage over the Italian territory (more than 10\ub0 in latitude and longitude, covering more than 3x105km2), the EEE network is the largest MRPC \u2013 based system for cosmic rays detection. Each MRPC has 6 gas gaps obtained by a stack of glass plate, spaced 250\u3bcm each, and is equipped with 24 copper strips. Since its beginning, the EEE MRPCs were filled with a gas mixture of 98% of tetrafluoroethane and 2% of sulfur hexafluoride, but recent restrictions on greenhouse gases have prompted the study of their performance with new gas mixtures. To this aim, extensive tests of tetrafluoropropene and carbon dioxide or sulfur hexafluoride gas mixtures have been carried out