Response of CdWO4 crystal scintillator for few MeV ions and low energy electrons

The response of a CdWO4 crystal scintillator to protons, alpha particles, Li, C, O and Ti ions with energies in the range 1 - 10 MeV was measured. The non-proportionality of CdWO4 for low energy electrons (4 - 110 keV) was studied with the Compton Coincidence Technique. The energy dependence of the quenching factors for ions and the relative light yield for low energy electrons was calculated using a semi-empirical approach. Pulse-shape discrimination ability between gamma quanta, protons, alpha particles and ions was investigated.Comment: 20 pages, 8 figs, accepted in Nucl. Instrum. Meth.

Transcriptional impairment of β-catenin/E-cadherin complex is not associated with β-catenin mutations in colorectal carcinomas

We report the absence of β-catenin mutations in 63 sporadic colorectal carcinomas (SCRCs) with demonstrated decreased β-catenin and E-cadherin mRNA expression and E-cadherin protein expression in a subset of carcinomas examined, suggesting that β-catenin mutations are an extremely rare phenomenon in SCRCs and are not responsible for the transcriptional impairment of the β-catenin/E-cadherin adhesion complex observed in these tumours

β-Catenin is a pH sensor with decreased stability at higher intracellular pH.

β-Catenin functions as an adherens junction protein for cell-cell adhesion and as a signaling protein. β-catenin function is dependent on its stability, which is regulated by protein-protein interactions that stabilize β-catenin or target it for proteasome-mediated degradation. In this study, we show that β-catenin stability is regulated by intracellular pH (pHi) dynamics, with decreased stability at higher pHi in both mammalian cells and Drosophila melanogaster β-Catenin degradation requires phosphorylation of N-terminal residues for recognition by the E3 ligase β-TrCP. While β-catenin phosphorylation was pH independent, higher pHi induced increased β-TrCP binding and decreased β-catenin stability. An evolutionarily conserved histidine in β-catenin (found in the β-TrCP DSGIHS destruction motif) is required for pH-dependent binding to β-TrCP. Expressing a cancer-associated H36R-β-catenin mutant in the Drosophila eye was sufficient to induce Wnt signaling and produced pronounced tumors not seen with other oncogenic β-catenin alleles. We identify pHi dynamics as a previously unrecognized regulator of β-catenin stability, functioning in coincidence with phosphorylation

Integrated Multimedia Timeline of Medical Images and Data for Thoracic Oncology Patients

A prototype multimedia medical database has been developed to provide image and textual data for thoracic oncology patients undergoing treatment of advanced malignancies. The database integrates image data from the hospital pieture archiving and communication system with textual reports from the radiology information system, alphanumeric data contained in the hospital information system, and other electronic medical data. The database presents information in a timeline format and also contains visualization programs that permit the user to view and annotate radiographic measurements in tabular or graphic form. The database provides an efficient and intuitive display of the changing status of oncology patients. The ability to integrate, manage, and access relevant multimedia information may substantially enhance communication among distributed multidisciplinary health care providers and may ensure greater consistency and completeness of patient-related data

A detector system for 'absolute' measurements of fission cross sections at n_TOF in the energy range below 200 MeV

A new measurement of the $^{235}$U(n,f) cross section was performed at the neutron time-of-flight facility n_TOF at CERN. The experiment focused on neutron energies from 20 MeV to several hundred MeV, and was normalized to neutron scattering on hydrogen. This is a measurement first of its kind at this facility, in an energy range that was until now not often explored, so the detector development phase was crucial for its success. Two detectors are presented, a parallel plate fission chamber (PPFC) and a recoil proton telescope (RPT), both dedicated to perform measurements in the incident neutron energy range from 30 MeV to 200 MeV. The experiment was designed to minimize statistical uncertainties in the allocated run time. Several efforts were made to ensure that the systematic effects were understood and under control. The results show that the detectors are suited for measurements at n_TOF above 30 MeV, and indicate the path for possible future lines of development.Comment: Added acknowledgement to Euratom fundin

RNA editing signature during myeloid leukemia cell differentiation

Adenosine deaminases acting on RNA (ADARs) are key proteins for hematopoietic stem cell self-renewal and for survival of differentiating progenitor cells. However, their specific role in myeloid cell maturation has been poorly investigated. Here we show that ADAR1 is present at basal level in the primary myeloid leukemia cells obtained from patients at diagnosis as well as in myeloid U-937 and THP1 cell lines and its expression correlates with the editing levels. Upon phorbol-myristate acetate or Vitamin D3/granulocyte macrophage colony-stimulating factor (GM-CSF)-driven differentiation, both ADAR1 and ADAR2 enzymes are upregulated, with a concomitant global increase of A-to-I RNA editing. ADAR1 silencing caused an editing decrease at specific ADAR1 target genes, without, however, interfering with cell differentiation or with ADAR2 activity. Remarkably, ADAR2 is absent in the undifferentiated cell stage, due to its elimination through the ubiquitin–proteasome pathway, being strongly upregulated at the end of the differentiation process. Of note, peripheral blood monocytes display editing events at the selected targets similar to those found in differentiated cell lines. Taken together, the data indicate that ADAR enzymes play important and distinct roles in myeloid cells

Impaired protein translation in Drosophila models for Charcot–Marie–Tooth neuropathy caused by mutant tRNA synthetases

Dominant mutations in five tRNA synthetases cause Charcot–Marie–Tooth (CMT) neuropathy, suggesting that altered aminoacylation function underlies the disease. However, previous studies showed that loss of aminoacylation activity is not required to cause CMT. Here we present a Drosophila model for CMT with mutations in glycyl-tRNA synthetase (GARS). Expression of three CMT-mutant GARS proteins induces defects in motor performance and motor and sensory neuron morphology, and shortens lifespan. Mutant GARS proteins display normal subcellular localization but markedly reduce global protein synthesis in motor and sensory neurons, or when ubiquitously expressed in adults, as revealed by FUNCAT and BONCAT. Translational slowdown is not attributable to altered tRNA[superscript Gly] aminoacylation, and cannot be rescued by Drosophila Gars overexpression, indicating a gain-of-toxic-function mechanism. Expression of CMT-mutant tyrosyl-tRNA synthetase also impairs translation, suggesting a common pathogenic mechanism. Finally, genetic reduction of translation is sufficient to induce CMT-like phenotypes, indicating a causal contribution of translational slowdown to CMT.National Institutes of Health (U.S.) (Grant GM17151

Design, construction, and beam tests of a rotatable collimator prototype for high-intensity and high-energy hadron accelerators

A rotatable-jaw collimator design was conceived as a solution to recover from catastrophic beam impacts which would damage a collimator at the Large Hadron Collider (LHC) or its High-Luminosity upgrade (HL-LHC). One such rotatable collimator prototype was designed and built at SLAC and delivered to CERN for tests with LHC-type circulating beams in the Super Proton Synchrotron (SPS). This was followed by destructive tests at the dedicated High Radiation to Materials (HiRadMat) facility to validate the design and rotation functionality. An overview of the collimator design, together with results from tests without and with beam are presented

Cross section measurements of 155,157Gd(n, γ) induced by thermal and epithermal neutrons

© SIF, Springer-Verlag GmbH Germany, part of Springer Nature 2019Neutron capture cross section measurements on 155Gd and 157Gd were performed using the time-of-flight technique at the n_TOF facility at CERN on isotopically enriched samples. The measurements were carried out in the n_TOF experimental area EAR1, at 185 m from the neutron source, with an array of 4 C6D6 liquid scintillation detectors. At a neutron kinetic energy of 0.0253 eV, capture cross sections of 62.2(2.2) and 239.8(8.4) kilobarn have been derived for 155Gd and 157Gd, respectively, with up to 6% deviation relative to values presently reported in nuclear data libraries, but consistent with those values within 1.6 standard deviations. A resonance shape analysis has been performed in the resolved resonance region up to 181 eV and 307 eV, respectively for 155Gd and 157Gd, where on average, resonance parameters have been found in good agreement with evaluations. Above these energies and up to 1 keV, the observed resonance-like structure of the cross section has been analysed and characterised. From a statistical analysis of the observed neutron resonances we deduced: neutron strength function of 2. 01 (28) × 10 - 4 and 2. 17 (41) × 10 - 4; average total radiative width of 106.8(14) meV and 101.1(20) meV and s-wave resonance spacing 1.6(2) eV and 4.8(5) eV for n + 155Gd and n + 157Gd systems, respectively.Peer reviewedFinal Accepted Versio