Carbon fragmentation measurements and validation of the GEANT4 nuclear reaction models for hadrontherapy

Nuclear fragmentation measurements are necessary when using heavy-ion beams in hadrontherapy to predict the effects of the ion nuclear interactions within the human body. Moreover, they are also fundamental to validate and improve the Monte Carlo codes for their use in planning tumor treatments. Nowadays, a very limited set of carbon fragmentation cross sections are being measured, and in particular, to our knowledge, no double-differential fragmentation cross sections at intermediate energies are available in the literature. In this work, we have measured the double-differential cross sections and the angular distributions of the secondary fragments produced in the C-12 fragmentation at 62 A MeV on a thin carbon target. The experimental data have been used to benchmark the prediction capability of the GEANT4 Monte Carlo code at intermediate energies, where it was never tested before. In particular, we have compared the experimental data with the predictions of two GEANT4 nuclear reaction models: the Binary Light Ions Cascade and the Quantum Molecular Dynamic. From the comparison, it has been observed that the Binary Light Ions Cascade approximates the angular distributions of the fragment production cross sections better than the Quantum Molecular Dynamic model. However, the discrepancies observed between the experimental data and the Monte Carlo simulations lead to the conclusion that the prediction capability of both models needs to be improved at intermediate energies

Construction and characterization of the detection modules for the Muon Portal Project

The Muon Portal Project is a joint initiative between research and industrial partners, aimed at the construction of a real size detector protoype (6×3×7 m3) for the inspection of containers by the muon scattering technique, devised to search for hidden high-Z fissile materials and provide a full 3D tomography of the interior of the container in a scanning time of the order of minutes. The muon tracking detector is based on a set of 48 detection modules (size 1 m × 3 m), each built with 100 extruded scintillator strips, so as to provide four X-Y detection planes, two placed above and two below the container to be inspected. Two wavelength shifting (WLS) fibres embedded in each strip convey the emitted photons to Silicon Photomultipliers (SiPM) which act as photosensors. After a research and development phase, which led to the choice and test of the individual components, the construction of the full size detector has already started. The paper describes the results of the mass characterization of the photosensors and the construction and test measurements of the first detection modules of the Project

The Muon Portal Double Tracker for the Inspection of Travelling Containers

The Muon Portal Project has as its goal the design and construction of a real-size working detector prototype in scale 1:1, to inspect the content of travelling containers by means of the secondary cosmic-ray muon radiation and to recognize high-Z hidden materials (i.e. U, Pu). The tomographic image is obtained by reconstructing the input and output trajectories of each muon when it crosses the container and, consequently, the scattering angle, making use of two trackers placed above and below the container. The scan is performed without adding any external radiation, in a reasonable time (few minutes) and with a good spatial and angular resolution. The detector consists of 8 planes each segmented in 6 identical modules. Each module is made of scintillating strips with two WaveLength Shifting fibers (WLS) inside, coupled to Silicon photomultipliers. The customized read-out electronics employs programmable boards. Thanks to a smart read-out system, the number of output channels is reduced by a factor 10. The signals from the front-end modules are sent to the read-out boards, in order to convert analog signals to digital ones, by comparison with a threshold. The data are pre-analyzed and stored into a data acquisition PC. After an intense measurement and simulation campaign to carefully characterize the detector components, the first detection modules ( 1 ×3 m2) have been already built. In this paper the detector architecture, particularly focusing on the used electronics and the main preliminary results will be presented. <P /

Comparative Genomic Analysis of Pathogenic and Probiotic Enterococcus faecalis Isolates, and Their Transcriptional Responses to Growth in Human Urine

Urinary tract infection (UTI) is the most common infection caused by enterococci, and Enterococcus faecalis accounts for the majority of enterococcal infections. Although a number of virulence related traits have been established, no comprehensive genomic or transcriptomic studies have been conducted to investigate how to distinguish pathogenic from non-pathogenic E. faecalis in their ability to cause UTI. In order to identify potential genetic traits or gene regulatory features that distinguish pathogenic from non-pathogenic E. faecalis with respect to UTI, we have performed comparative genomic analysis, and investigated growth capacity and transcriptome profiling in human urine in vitro. Six strains of different origins were cultivated and all grew readily in human urine. The three strains chosen for transcriptional analysis showed an overall similar response with respect to energy and nitrogen metabolism, stress mechanism, cell envelope modifications, and trace metal acquisition. Our results suggest that citrate and aspartate are significant for growth of E. faecalis in human urine, and manganese appear to be a limiting factor. The majority of virulence factors were either not differentially regulated or down-regulated. Notably, a significant up-regulation of genes involved in biofilm formation was observed. Strains from different origins have similar capacity to grow in human urine. The overall similar transcriptional responses between the two pathogenic and the probiotic strain suggest that the pathogenic potential of a certain E. faecalis strain may to a great extent be determined by presence of fitness and virulence factors, rather than the level of expression of such traits

Expanding primary cells from mucoepidermoid and other salivary gland neoplasms for genetic and chemosensitivity testing

Restricted availability of cell and animal models is a rate-limiting step for investigation of salivary gland neoplasm pathophysiology and therapeutic response. Conditionally reprogrammed cell (CRC) technology enables establishment of primary epithelial cell cultures from patient material. This study tested a translational workflow for acquisition, expansion and testing of CRC-derived primary cultures of salivary gland neoplasms from patients presenting to an academic surgical practice. Results showed that cultured cells were sufficient for epithelial cell-specific transcriptome characterization to detect candidate therapeutic pathways and fusion genes, and for screening for cancer risk-associated single nucleotide polymorphisms (SNPs) and driver gene mutations through exome sequencing. Focused study of primary cultures of a low-grade mucoepidermoid carcinoma demonstrated amphiregulin-mechanistic target of rapamycin-protein kinase B (AKT; AKT1) pathway activation, identified through bioinformatics and subsequently confirmed as present in primary tissue and preserved through different secondary 2D and 3D culture media and xenografts. Candidate therapeutic testing showed that the allosteric AKT inhibitor MK2206 reproducibly inhibited cell survival across different culture formats. By contrast, the cells appeared resistant to the adenosine triphosphate competitive AKT inhibitor GSK690693. Procedures employed here illustrate an approach for reproducibly obtaining material for pathophysiological studies of salivary gland neoplasms, and other less common epithelial cancer types, that can be executed without compromising pathological examination of patient specimens. The approach permits combined genetic and cell-based physiological and therapeutic investigations in addition to more traditional pathologic studies, and can be used to build sustainable bio-banks for future inquiries. This article has an associated First Person interview with the first author of the paper