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IFMIF-DONES is a facility under construction in Granada, whose main goal is the validation and characterization of materials under a fusion prototypic irradiation field. This field is created by the interaction of a high energy intense continuous deuteron beam and a flowing liquid lithium target. The requirements imposed on the beam at the interaction point are a complex trade-off among the scientific experimental needs for the materials irradiation defined at the top-level requirements (20 dpa in a volume of 0.3 dm3 and 50 dpa in 0.1 dm3), and the technical constraints of several systems such as the Accelerator Systems, the Lithium Systems, and the Test Systems. Recent simulations with the initial definition of beam-on-target requirements showed the necessity of redefining them in order to fulfill the irradiation needs. This contribution will address the main challenges to gather the inputs for the definition and reassessment of the beam-on-target requirements. A comparison detailing the main changes compared to the previous ones will be given, together with a short overview of the studies ongoing by different systems to analyze the impact of each beam-on-target requirements on the performance of the whole facility.

Abstract Small airway remodeling (SAR) is a key phenomenon of airflow obstruction in smokers, leading to chronic obstructive pulmonary disease (COPD). SAR results in an increased thickness of small airway walls, with a combination of peribronchiolar fibrosis with increased fibrous tissue and accumulation of mesenchymal and epithelial cells. SAR pathogenesis is still unclear but recent data suggest that alterations in telomerase activity could represent a possible underlying mechanism of SAR. Our study was dedicated to identify a potential protective role of TA-65, a pharmacological telomerase activator, in a cigarette smoke (CS) model of SAR in mice, and to further precise if extra-telomeric effects of telomerase, involving oxidative stress modulation, could explain it. C57BL/6J mice were daily exposed to air or CS during 4 weeks with or without a concomitant administration of TA-65 starting 7 days before CS exposure. Morphological analyses were performed, and mucus production, myofibroblast differentiation, collagen deposition, as well as transforming growth factor-β1 (TGF-β1) expression in the small airway walls were examined. In addition, the effects of TA-65 treatment on TGF-β expression, fibroblast-to-myofibroblast differentiation, reactive oxygen species (ROS) production and catalase expression and activity were evaluated in primary cultures of pulmonary fibroblasts and/or mouse embryonic fibroblasts in vitro. Exposure to CS during 4 weeks induced SAR in mice, characterized by small airway walls thickening and peribronchiolar fibrosis (increased deposition of collagen, expression of α-SMA in small airway walls), without mucus overproduction. Treatment of mice with TA-65 protected them from CS-induced SAR. This effect was associated with the prevention of CS-induced TGF-β expression in vivo, the blockade of TGF-β-induced myofibroblast differentiation, and the reduction of TGF-β-induced ROS production that correlates with an increase of catalase expression and activity. Our findings demonstrate that telomerase is a critical player of SAR, probably through extra-telomeric anti-oxidant effects, and therefore provide new insights in the understanding and treatment of COPD pathogenesis.