Children and adolescents treated with neridronate for osteogenesis imperfecta show no evidence of any osteonecrosis of the jaw

Over recent years, several reports have been published on unusual cases of osteonecrosis of the jaw (ONJ) in adults using second- and third-generation nitrogen-containing bisphosphonates such as pamidronate, alendronate, risedronate and zoledronate, but no case has ever been reported either in children or in adult patients taking neridronate. Children and adolescents affected by osteogenesis imperfecta (OI) could belong to a high-risk group for ONJ because bone fragility in OI is associated with a connective tissue malfunction. The purpose of this study is to evaluate the incidence of ONJ in a pediatric population treated with neridronate for OI. A total of 102 pediatric patients with OI who received neridronate infusions for a mean of 6.81 years (SD \ub1 3.06 years) were clinically assessed for possible ONJ. Eligibility criteria for participation included patients between 1.2 and 24 years old who received cyclical neridronate infusions for at least 1 year. All the patients were reviewed to determine duration, dosage and cumulative dose of their bisphosphonate therapy and were examined clinically to assess their oral health status. We have not demonstrated any occurrence of ONJ in our patients. In conclusion, at the moment insufficient data are available to prove a greater risk of ONJ in children with OI than in children affected by other forms of bone fragility. However, cases may emerge in future because the risk of ONJ seems to be related to the cumulative dose and the duration of therap

New Insights into the Molecular Mechanism of E-Cadherin-Mediated Cell Adhesion by Free Energy Calculations

Three-dimensional domain swapping is an important mode of protein association leading to the formation of stable dimers. Monomers associating via this mechanism mutually exchange a domain to form a homodimer. Classical cadherins, an increasingly important target for anticancer therapy, use domain swapping to mediate cell adhesion. However, despite its importance, the molecular mechanism of domain swapping is still debated. Here, we study the conformational changes that lead to activation and dimerization via domain swapping of E-cadherin. Using state-of-the-art enhanced sampling atomistic simulations, we reconstruct its conformational free energy landscape, obtaining the free energy profile connecting the inactive and active form. Our simulations predict that the E-cadherin monomer populates the open and closed forms almost equally, which is in agreement with the proposed “selected fit” mechanism in which monomers in an active conformational state bind to form a homodimer, analogous to the conformational selection mechanism often observed in ligand–target binding. Moreover, we find that the open state population is increased in the presence of calcium ions at the extracellular boundary, suggesting their possible role as allosteric activators of the conformational change

A novel background reduction strategy for high level triggers and processing in gamma-ray Cherenkov detectors

Gamma ray astronomy is now at the leading edge for studies related both to fundamental physics and astrophysics. The sensitivity of gamma detectors is limited by the huge amount of background, constituted by hadronic cosmic rays (typically two to three orders of magnitude more than the signal) and by the accidental background in the detectors. By using the information on the temporal evolution of the Cherenkov light, the background can be reduced. We will present here the results obtained within the MAGIC experiment using a new technique for the reduction of the background. Particle showers produced by gamma rays show a different temporal distribution with respect to showers produced by hadrons; the background due to accidental counts shows no dependence on time. Such novel strategy can increase the sensitivity of present instruments.Comment: 4 pages, 3 figures, Proc. of the 9th Int. Syposium "Frontiers of Fundamental and Computational Physics" (FFP9), (AIP, Melville, New York, 2008, in press

INFN Camera demonstrator for the Cherenkov Telescope Array

The Cherenkov Telescope Array is a world-wide project for a new generation of ground-based Cherenkov telescopes of the Imaging class with the aim of exploring the highest energy region of the electromagnetic spectrum. With two planned arrays, one for each hemisphere, it will guarantee a good sky coverage in the energy range from a few tens of GeV to hundreds of TeV, with improved angular resolution and a sensitivity in the TeV energy region better by one order of magnitude than the currently operating arrays. In order to cover this wide energy range, three different telescope types are envisaged, with different mirror sizes and focal plane features. In particular, for the highest energies a possible design is a dual-mirror Schwarzschild-Couder optical scheme, with a compact focal plane. A silicon photomultiplier (SiPM) based camera is being proposed as a solution to match the dimensions of the pixel (angular size of ~ 0.17 degrees). INFN is developing a camera demonstrator made by 9 Photo Sensor Modules (PSMs, 64 pixels each, with total coverage 1/4 of the focal plane) equipped with FBK (Fondazione Bruno Kessler, Italy) Near UltraViolet High Fill factor SiPMs and Front-End Electronics (FEE) based on a Target 7 ASIC, a 16 channels fast sampler (up to 2GS/s) with deep buffer, self-trigger and on-demand digitization capabilities specifically developed for this purpose. The pixel dimensions of $6\times6$ mm$^2$ lead to a very compact design with challenging problems of thermal dissipation. A modular structure, made by copper frames hosting one PSM and the corresponding FEE, has been conceived, with a water cooling system to keep the required working temperature. The actual design, the adopted technical solutions and the achieved results for this demonstrator are presented and discussed.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589

Design of a SiPM-based cluster for the Large Size Telescope camera of CTA

A Silicon Photomultiplier (SiPM)-based photodetector is being built to demonstrate its feasibility for an alternative silicon-based camera design for the Large Size Telescope (LST) of the Cherenkov Telescope Array. It has been designed to match the size of the standard Photomultiplier Tube (PMT) cluster unit and to be compatible with mechanics, electronics and focal plane optics of the first LST camera. Here, we describe the overall SiPM cluster design along with the main differences with respect to the currently used PMT cluster unit. The fast electronics of the SiPM pixel and its layout are also presented. In order to derive the best working condition for the final unit, we measured the SiPM performances in terms of gain, photo-detection efficiency and cross-talk. One pixel, a unit of 14 SiPMs, has been built. We will discuss also some preliminary results regarding this device and we will highlight the future steps of this project.Comment: submitted to NIM

Sensitivity of simulated soil water content, evapotranspiration, gross primary production and biomass to climate change factors in Euro-Mediterranean grasslands

Grassland models often yield more uncertain outputs than arable crop models due to more complex interactions and the largely undocumented sensitivity of grassland models to environmental factors. The aim of the present study was to assess the impact of single-factor changes in temperature, precipitation, and atmospheric [CO2] on simulated soil water content (SWC), actual evapotranspiration (ET), gross primary production (GPP) and yield biomass, and also to link the sensitivity analysis with experimental results. We employed an unprecedented multi-model framework consisting of seven grassland models at nine sites with different environmental characteristics in Europe and Israel, with two management options at three sites. For warming/cooling and wetting/drying, models showed general consistency in the direction of SWC and ET changes, but less agreement regarding GPP and biomass changes. The simulated responses consistently revealed an overall positive effect of CO2 enrichment on GPP and biomass, while the direction of change differed for SWC and ET. Comparing with single-factor experimental manipulations, SWC simulations slightly underestimated the observed effect of warming, while the overall mean model sensitivity for biomass (+7.5%) closely matched the mean response observed with 1–2 °C warming (+6.6%). The models exhibited lower sensitivity of SWC to wetting or drying compared to the experiments. The overall mean sensitivity of biomass to drying was -4.3%, contrasting with the mean experimental effect size of -9.6%, which proved to be more realistic than the mean wetting effect (+3.2%, against +38.9% in the field trials). The simulated sensitivity of SWC to CO2 enrichment was markedly underestimated, while the biomass response (+12.0%) closely matched the observations (+17.5%). Although the multi-model averaging did not manifestly improve the realism of the simulations, it ensured a realistic response in the direction of change to varying conditions. The results suggest a paradigm shift in grassland modelling meaning that the usual practice of model optimisation/validation needs to be complemented by a sensitivity analysis following the approach presented. The results also highlight the importance of model improvements, especially in terms of soil hydrology representation, a key environmental driver of grassland functioning

Impacts of Climate Change on SOC Dynamic and Crop Yield of Italian Rainfed Wheat-Maize Cropping Systems Managed with Conventional or Conservation Tillage Practices

There is still uncertainty on the ability of conservation tillage (i.e., reduced- RT and no till - NT) in contributing to the resilience of cropping systems to climate change pressures (Powlson et al 2016). RT or NT can improve soil physical and biological proprieties thus increasing water holding capacity and fertility, stabilizing soil structure and enhancing soil biodiversity and functions. They are also frequently proposed as mitigation practices as they can contribute to increase soil organic carbon (SOC) compared to conventional moldboard ploughing practices (Gonzalez-Sanchezet al., 2012). However, SOC increase occurs mostly in the upper soil layer but not always in the deeper profile (Haddaway et al., 2016) where SOC measurements are less frequently measured. In this study, we used data obtained from long term field experiments(LTE) coupled with three crop simulation models in order to assess the long-term effects of different tillage management practices on crop yield and on changes in SOC stocks in both superficial (0-20cm) and deeper layers (20-50cm) in Mediterranean rainfed cereal cropping systems at current and future climate scenarios