A new parasitic, mixed-field, neutron-dominated irradiation station has been recently commissioned at the European Laboratory for Particle Physics (CERN). The station is installed within the neutron time-of-flight (n_TOF) facility, taking advantage of the secondary radiation produced by the neutron spallation target, with neutrons ranging from 0.025 eV to several hundreds of MeV. The new station allows radiation damage studies to be performed in irradiation conditions that are closer to the ones encountered during the operation of particle accelerators; the irradiation tests carried out in the station will be complementary to the standard tests on materials, usually performed with gamma sources. Samples will be exposed to neutron-dominated doses in the MGy range per year, with minimal impact on the n_TOF facility operation. The station has 24 irradiation positions, each hosting up to $100{\mathrm{cm}}^3$ of sample material. In view of its proximity to the n_TOF target, inside protective shielding, the irradiation station and its operating procedures have been carefully developed taking into account the safety of personnel and to avoid any unwanted impact on the operation of the n_TOF facility and experiments. Due to the residual radioactivity of the whole area around the n_TOF target and of the irradiated samples, access to the irradiation station is forbidden to human operators even when the n_TOF facility is not in operation. Robots are used for the remote installation and retrieval of the samples, and other optimizations of the handling procedures were developed in compliance with radiation protection regulations and the aim of minimizing doses to personnel. The sample containers were designed to be radiation tolerant, compatible with remote handling, and subject to detailed risk analysis and testing during their development. The whole life cycle of the irradiated materials, including their post-irradiation examinations and final disposal, was considered and optimized.

Two 6 t beam dumps, made of a graphite core encapsulated in a stainless steel vessel, are used to absorb the energy of the two Large Hadron Collider (LHC) intense proton beams during operation of the accelerator. Operational issues started to appear in 2015 during LHC Run 2 (2014–2018) as a consequence of the progressive increase of the LHC beam kinetic energy, necessitating technical interventions in the highly radioactive areas around the dumps. Nitrogen gas leaks appeared after highly energetic beam impacts and instrumentation measurements indicated an initially unforeseen movement of the dumps. A computer modelling analysis campaign was launched to understand the origin of these issues, including both Monte Carlo simulations to model the proton beam interaction as well as advanced thermo-mechanical analyses. The main findings were that the amount of instantaneous energy deposited in the dump vessel leads to a strong dynamic response of the whole dump and high accelerations (above 200 g). Based on these findings, an upgraded design, including a new support system and beam windows, was implemented to ensure the dumps' compatibility with the more intense beams foreseen during LHC Run 3 (2022–2025) of 539 MJ per beam. In this paper an integral overview of the operational behaviour of the dumps and the upgraded configurations are discussed.

Background: For hepatocellular carcinoma (HCC), effective therapeutic approaches are lacking. As aberrant gene methylation is a major contributor to HCC development, demethylating drugs such as 5-azacytidine (5-Aza) have been proposed. As most 5-Aza mechanisms of action are unknown, we investigated its phenotypic/molecular effects. Methods: 5-Aza effects were examined in the human HCC cell lines JHH-6/HuH-7 and in the rat cell-line N1-S1. We also employed a xenograft mouse model (HuH-7), a zebrafish model (JHH-6), and an orthotopic syngeneic rat model (N1-S1) of HCC. Results: 5-Aza downregulated cell viability/growth/migration/adhesion by upregulating miR-139-5p, which in turn downregulated ROCK2/cyclin D1/E2F1 and increased p27^kip1, resulting in G1/G0 cell accumulation. Moreover, a decrease in cyclin B1 and an increase in p27^kip1 led to G2/M accumulation. Finally, we observed a decrease in MMP-2 levels, a stimulator of HCC cell migration. Aza effects were confirmed in the mouse model; in the zebrafish model, we also demonstrated the downregulation of tumor neo-angiogenesis, and in the orthotopic rat model, we observed impaired N1-S1 grafting in a healthy liver. Conclusion: We demonstrate for the first time that 5-Aza can impair HCC development via upregulation of miR-139-5p, which in turn impairs the ROCK2/cyclin D1/E2F1/cyclin B1 pro-proliferative pathway and the ROCK2/MMP-2 pro-migratory pathway. Thus, we provide novel information about 5-Aza mechanisms of action and deepen the knowledge about the crosstalk among ROCK2/cyclin D1/E2F1/cyclin B1/p27^kip1/MMP-2 in HCC.

Three-dimensional (3D) bioprinting allows the production of artificial 3D cellular microenvironments thanks to the controlled spatial deposition of bioinks. Proper bioink characterization is required to achieve the essential characteristics of printability and biocompatibility for 3D bioprinting. In this work, a protocol to standardize the experimental characterization of a new bioink is proposed. A functionalized hydrogel based on gelatin and chitosan was used. The protocol was divided into three steps: pre-printing, 3D bioprinting, and post-printing. For the pre-printing step, the hydrogel formulation and its repeatability were evaluated. For the 3D-bioprinting step, the hydrogel-printability performance was assessed through qualitative and quantitative tests. Finally, for the post-printing step, the hydrogel biocompatibility was investigated using UMR-106 cells. The hydrogel was suitable for printing grids with good resolution from 4 h after the cross-linker addition. To guarantee a constant printing pressure, it was necessary to set the extruder to 37 °C. Furthermore, the hydrogel was shown to be a valid biomaterial for the UMR-106 cells’ growth. However, fragmentation of the constructs appeared after 14 days, probably due to the negative osteosarcoma-cell interference. The protocol that we describe here denotes a strong approach to bioink characterization to improve standardization for future biomaterial screening and development.