Behaviour in Magnetic Fields of Fast Conventional and Fine-Mesh Photomultipliers

The performance of both conventional and fine-mesh Hamamatsu photomultipliers has been measured inside moderate magnetic fields. This has allowed the test of effective shielding solutions for photomultipliers, to be used in time-of-flight detectors based on scintillation counters. Both signal amplitude reduction or deterioration of the timing properties inside magnetic fields have been investigated

Activation of WNT and BMP signaling in adult human articular cartilage following mechanical injury

Peer reviewedPublisher PD

Cellular therapy and tissue engineering for cartilage repair

Funding The authors are grateful to the Medical Research Council (grant numbers MR/L020211/1 and MR/L022893/1; CDB, AJR), Versus Arthritis (formerly Arthritis Research UK, grant numbers 20050, 20775, 20865, 21156, and 21800; CDB, AJR), Biosplice Therapeutics (CDB, AJR), and the Canadian Institute of Health Research (AZ, RAK) for supporting their research.Peer reviewedproo

The polyphenols resveratrol and epigallocatechin-3-gallate restore the severe impairment of mitochondria in hippocampal progenitor cells from a Down syndrome mouse model.

Mitochondrial dysfunctions critically impair nervous system development and are potentially involved in the pathogenesis of various neurodevelopmental disorders, including Down syndrome (DS), the most common genetic cause of intellectual disability. Previous studies from our group demonstrated impaired mitochondrial activity in peripheral cells from DS subjects and the efficacy of epigallocatechin-3-gallate (EGCG) - a natural polyphenol major component of green tea - to counteract the mitochondrial energy deficit. In this study, to gain insight into the possible role of mitochondria in DS intellectual disability, mitochondrial functions were analyzed in neural progenitor cells (NPCs) isolated from the hippocampus of Ts65Dn mice, a widely used model of DS which recapitulates many major brain structural and functional phenotypes of the syndrome, including impaired hippocampal neurogenesis. We found that, during NPC proliferation, mitochondrial bioenergetics and mitochondrial biogenic program were strongly compromised in Ts65Dn cells, but not associated with free radical accumulation. These data point to a central role of mitochondrial dysfunction as an inherent feature of DS and not as a consequence of cell oxidative stress. Further, we disclose that, besides EGCG, also the natural polyphenol resveratrol, which displays a neuroprotective action in various human diseases but never tested in DS, restores oxidative phosphorylation efficiency and mitochondrial biogenesis, and improves proliferation of NPCs. These effects were associated with the activation of PGC-1α/Sirt1/AMPK axis by both polyphenols. This research paves the way for using nutraceuticals as a potential therapeutic tool in preventing or managing some energy deficit-associated DS clinical manifestations

Time of flight detectors with SiPMT array readout

none6noTime-of-flight detectors, based on scintillation counters, may use conventional photomultipliers for the readout. Problems arise in presence of external magnetic fields. SiPMT arrays are insensitive to magnetic fields and may be a suitable option to replace photomultipliers. Timing performances for several types of SiPMT arrays have been studied and results are presented.Bonesini, M; Bertoni, R.; de Bari, A.; Nardò, R.; Prata, M.; Rossella, M.Bonesini, M; Bertoni, R.; DE BARI, Antonio; Nardo', Roberto; Prata, M.; Rossella, M

The design and commissioning of the MICE upstream time-of-flight system

In the MICE experiment at RAL the upstream time-of-flight detectors are used for particle identification in the incoming muon beam, for the experiment trigger and for a precise timing (sigma_t ~ 50 ps) with respect to the accelerating RF cavities working at 201 MHz. The construction of the upstream section of the MICE time-of-flight system and the tests done to characterize its individual components are shown. Detector timing resolutions ~50-60 ps were achieved. Test beam performance and preliminary results obtained with beam at RAL are reported.Comment: accepted on Nuclear Instruments and Methods

A homeostatic function of CXCR2 signalling in articular cartilage

Funding This work was funded by Arthritis Research UK (grants 17859, 17971, 19654), INNOCHEM EU FP6 (grant LSHB-CT-2005-51867), MRC (MR/K013076/1) and the William Harvey Research FoundationPeer reviewedPublisher PD

Time, frequency and information domain analysis of heart period and QT variability in asymptomatic long QT syndrome type 2 patients.

none8siThis study was designed to characterize in time, frequency and information domains heart period (HP) and QT interval variabilities in asymptomatic (ASYMP) long QT syndrome type 2 (LQT2) subjects. HP, approximated as the temporal distance between two consecutive R-wave peaks, and QT, approximated as the temporal distance between the R-wave peak and the T-wave offset, were automatically derived from 24h Holter recordings in 10 ASYMP LQT2 patients and 13 healthy non mutation carriers (NMC) subjects. All analyses were carried out during DAY (from 2 to 6 PM) and NIGHT (from 12 to 4 AM). Mean, variance, spectral power and complexity indices at short, medium and long time scales were assessed over HP and QT beat-to-beat series. Circadian rhythmicity was evident in both NMC and ASYMP LQT2 but ASYMP LQT2 subjects were characterized by higher HP, QT interval and HP variability during both DAY and NIGHT. In addition, multiscale complexity analysis was able to differentiate the groups by showing a higher HP complexity and a lower QT complexity at long time scales in ASYMP LQT2 during DAY. ASYMP LQT2 exhibited a different autonomic control compared to NMC and such a differentiation could be protective and assure them a lower risk profile.Bari V, 11.; Girardengo, G; Marchi, A; De Maria, B; Brink, Pa; Crotti, L; Schwartz, Pj; Porta, ABari V, 1. 1.; Girardengo, Giulia; Marchi, A; De Maria, B; Brink, Pa; Crotti, Lia; Schwartz, Peter; Porta, A

Overview of the predictive value of quantitative 18 FDG PET in head and neck cancer treated with chemoradiotherapy.

18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) allows to quantify the metabolic activity of a tumor (glycolysis) and has become a reference tool in oncology for the staging, restaging, radiotherapy planning and monitoring response in many cancers. Quantitative analyses have been introduced in order to overcome some of the limits of the visual methods, allowing an easier and more objective comparison of the inter- and intra-patients variations. The aims of this review were to report available evidences on the clinical value of quantitative PET/CT parameters in HNC. Forty-five studies, for a total of 2928 patients, were analyzed. Most of the data available dealt with the intensity of the metabolism, calculated from the Standard Uptake Value (SUV). Metabolic Tumor Volume (MTV) was well correlated with overall survival and disease free survival, with a higher predictive value than the maximum SUV. Spatial distribution of metabolism and textural analyses seems promising

Ezetimibe: Its Novel Effects on the Prevention and the Treatment of Cholesterol Gallstones and Nonalcoholic Fatty Liver Disease

The cholesterol absorption inhibitor ezetimibe can significantly reduce plasma cholesterol concentrations by inhibiting the Niemann-Pick C1-like 1 protein (NPC1L1), an intestinal sterol influx transporter that can actively facilitate the uptake of cholesterol for intestinal absorption. Unexpectedly, ezetimibe treatment also induces a complete resistance to cholesterol gallstone formation and nonalcoholic fatty liver disease (NAFLD) in addition to preventing hypercholesterolemia in mice on a Western diet. Because chylomicrons are the vehicles with which the enterocytes transport cholesterol and fatty acids into the body, ezetimibe could prevent these two most prevalent hepatobiliary diseases possibly through the regulation of chylomicron-derived cholesterol and fatty acid metabolism in the liver. It is highly likely that there is an intestinal and hepatic cross-talk through the chylomicron pathway. Therefore, understanding the molecular mechanisms whereby cholesterol and fatty acids are absorbed from the intestine could offer an efficacious novel approach to the prevention and the treatment of cholesterol gallstones and NAFLD