Activating NOTCH1 mutations occur in ~60% of human T-cell acute lymphoblastic leukemias (T-ALLs), and mutations disrupting the transcription factor IKZF1 (IKAROS) occur in ~5% of cases. To ...investigate the regulatory interplay between these driver genes, we have used a novel transgenic RNA interference mouse model to produce primary T-ALLs driven by reversible Ikaros knockdown. Restoring endogenous Ikaros expression in established T-ALL in vivo acutely represses Notch1 and its oncogenic target genes including Myc, and in multiple primary leukemias causes disease regression. In contrast, leukemias expressing high levels of endogenous or engineered forms of activated intracellular Notch1 (ICN1) resembling those found in human T-ALL rapidly relapse following Ikaros restoration, indicating that ICN1 functionally antagonizes Ikaros in established disease. Furthermore, we find that IKAROS mRNA expression is significantly reduced in a cohort of primary human T-ALL patient samples with activating NOTCH1/FBXW7 mutations, but is upregulated upon acute inhibition of aberrant NOTCH signaling across a panel of human T-ALL cell lines. These results demonstrate for the first time that aberrant NOTCH activity compromises IKAROS function in mouse and human T-ALL, and provide a potential explanation for the relative infrequency of IKAROS gene mutations in human T-ALL.
The purpose of the MU-RAY project is to develop an innovative approach to the study of volcanoes and their monitoring based on a particle physics approach. The test site is Vesuvio: one of the higher ...risk volcanoes in the world. In this context, muon radiography is an innovative method of enormous impact. This is an imaging technique which relies on the measurement, by means of a cosmic ray telescope, of the absorption in the volcano of muons with near-horizontal trajectories, produced by the interactions of cosmic rays with the atmosphere. Since 2003 this technique has been successfully used on volcanoes in Japan, providing pictures of their vertices with resolutions much better than those obtained with the traditional techniques based on gravimeters. Researchers from Naples and Florence are currently involved in the construction and testing of a prototype telescope based on the use of bars of plastic scintillator with a triangular section whose scintillation light is collected by special fibres (wave length shifters) and transported to SiPM (Silicon photomultipliers). A complete prototype telescope, consisting of three xy scintillation planes and 1m2 active area has been assembled and is now under test.
The muographic imaging of volcanoes relies on the measured transmittance of the atmospheric muon flux through the target. An important bias affecting the result comes from background contamination ...mimicking a higher transmittance. The MU‐RAY and TOMUVOL collaborations measured independently in 2013 the atmospheric muon flux transmitted through the Puy de Dôme volcano using their early prototype detectors, based on plastic scintillators and on Glass Resistive Plate Chambers, respectively. These detectors had three (MU‐RAY) or four (TOMUVOL) detection layers of 1 m2 each, tens (MU‐RAY) or hundreds (TOMUVOL) of nanosecond time resolution, a few millimeter position resolution, an energy threshold of few hundreds MeV, and no particle identification capabilities. The prototypes were deployed about 1.3 km away from the summit, where they measured, behind rock depths larger than 1000 m, remnant fluxes of 1.83±0.50(syst)±0.07(stat) m−2 d−1 deg−2 (MU‐RAY) and 1.95±0.16(syst)±0.05(stat) m−2 d−1 deg−2 (TOMUVOL), that roughly correspond to the expected flux of high‐energy atmospheric muons crossing 600 meters water equivalent (mwe) at 18° elevation. This implies that imaging depths larger than 500 mwe from 1 km away using such prototype detectors suffer from an overwhelming background. These measurements confirm that a new generation of detectors with higher momentum threshold, time‐of‐flight measurement, and/or particle identification is needed. The MU‐RAY and TOMUVOL collaborations expect shortly to operate improved detectors, suitable for a robust muographic imaging of kilometer‐scale volcanoes.
Key Point
The feasibility of muon imaging of km thick volcanoes was checked using two different detectors
The MU-RAY detector for muon radiography of volcanoes Anastasio, A.; Ambrosino, F.; Basta, D. ...
Nuclear Instruments and Methods in Physics Research Section A: Accelerators, Spectrometers, Detectors and Associated Equipment,
12/2013, Letnik:
732
Journal Article, Conference Proceeding
Recenzirano
The MU-RAY detector has been designed to perform muon radiography of volcanoes. The possible use on the field introduces several constraints. First the electric power consumption must be reduced to ...the minimum, so that the detector can be solar-powered. Moreover it must be robust and transportable, for what concerns the front-end electronics and data acquisition. A 1m2 prototype has been constructed and is taking data at Mt. Vesuvius. The detector consists of modules of 32 scintillator bars with wave length shifting fibers and silicon photomultiplier read-out. A dedicated front-end electronics has been developed, based on the SPIROC ASIC. An introduction to muon radiography principles, the MU-RAY detector description and results obtained in laboratory will be presented.
The MURAVES (MUon RAdiography of VESuvius) project is a joint activity participated by INGV, INFN and the Universities of Naples “Federico II” and Florence. The collaboration, following the ...experience gained within the previous INFN R&D project Mu-Ray, is currently completing the production of a robust four square meter low power consumption detector to be installed on the flank of Mount Vesuvius, an active volcano located on the western coast of Italy. The detector is supposed to collect data for at least one year, thus allowing performing a scan of the structure of the Vesuvius volcanic cone. In this work the status of the project and some parallel activities on muon radiography are presented.
Transcranial direct-current stimulation (tDCS) is a form of neurostimulation in which a constant, low current is delivered directly to the brain area of interest by small electrodes. The overall aim ...of this study was to examine and monitor the modulation of brain activity by electroencephalogram (EEG) in the frequency domain during tDCS in the resting state. To this end, we considered the modulation of spontaneous EEG to be a marker of the perturbation that was induced through the direct current (1.5 mA for 15 min). In all conditions (anodal, cathodal, and sham), an active electrode was placed over the right posterior parietal cortex, and a reference electrode was placed on the ipsilateral deltoid muscle. The EEG was recorded using a 64-channel system. The effect of tDCS was limited to the alpha rhythm, and the anodal stimulation significantly affected the alpha rhythm, whereas the cathodal stimulation did not elicit any modifications. Further, we observed modulation of alpha activity in areas that were stimulated directly through tDCS and in anterior noncontiguous areas. Finally, the anodal effect peaked 7.5 min after stimulation and decreased gradually over time. Our study demonstrates that in the resting brain, monocephalic anodal tDCS over posterior parietal areas alters ongoing brain activity, specifically in the alpha band rhythm. Our data can be used to fine-tune tDCS protocols in neurorehabilitation settings.
The necessary integration of renewable based technologies in the current energy systems is leading to a faster development of energy storage technologies. As widely known, renewables suffer for ...unpredictability, and their massive utilization is significantly affecting grid stability and management. In this framework, the development of efficient and large electrical storage systems is becoming a pivotal point to achieve a stable electrical network based on renewables. This paper proposes a novel approach to reduce the energy excesses exported to the grid by a residential user equipped with a100 kW solar photovoltaic field. In particular, the electricity is stored as hydrogen by means of a 50 kW reversible solid oxide fuel cell. A comprehensive energy and economic simulation model of the system is proposed. In particular, a model of the reversible solid oxide fuel cell is developed in MatLab® and then integrated in TRNSYS17 for dynamic simulation purpose. Results showed that using the plant waste heat is crucial for improving fuel cell efficiency and plant energy performance. The proposed system achieves a reduction of the primary energy consumption by 74%. However, the proposed plant exhibits a poor economic profitability, with a payback period of 15 years.
•Novel paradigm for residential electric energy storage based on hydrogen technology.•Hydrogen as electric energy storage system is able to shave the peak of power demand and production.•Very profitable energy and environmental results are achieved.•The high capital cost of hydrogen related technologies limits the economic profitably of such plants.
Dynamic simulation is a powerful tool for accurately evaluating the thermal demands of buildings and assessing the impact of energy refurbishment actions on their final consumption. Conversely, ...semi-stationary models are widely adopted in commercial applications for its simplified approach, which reduce calculation times, resulting in standardized results showing a certain deviation with respect to the real energy This paper presents the energy and economic comparison between the dynamic simulation and semi-stationary approaches for the calculation of primary energy demand of residential buildings. The semi-stationary method, used by the legislation to calculate the buildings energy label, is based on an energy performance parameter, not representative of the real energy demand. Conversely, an approach based on dynamic simulation provides a more reliable estimation of the primary energy demand. The main novelty of this paper is to numerically prove that the energy and economic savings calculated by means of software based on the current legislation may be overestimated. In this work, the dynamic simulation of the building-plant system is performed by TRaNsient SYstem Simulation (TRNSYS) program. Each building apartment is divided in thermal zones, where the internal heat gains are defined in detail. The semi-stationary simulation of the building-plant system is performed according to the Italian standard UNI TS 11300. The models allow one to evaluate the yearly primary energy demand, along with the energy bill and CO2 emissions. A specific case study is developed for a residential building located in Naples (Italy). The models are used to calculate the building energy demand for several scenarios, considering different thermal transmittances of the building elements. The results show that the semi-stationary method overestimates of primary energy saving, equal to 64.7 %, with respect to the one calculated with the dynamic approach, equal to 43.2 %.
•Semi-stationary and dynamic simulations were compared for residential buildings.•Critical evaluation of energy and economic savings due to the building refurbishment.•Primary energy savings of 65 % and 43 % by semi-stationary and dynamic simulation.•Dynamic simulation is needed within the legal frame of energy efficient buildings.
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