Downregulation of NOX4 Expression by Roflumilast N-Oxide Reduces Markers of Fibrosis in Lung Fibroblasts

The phosphodiesterase 4 inhibitor roflumilast prevents bleomycin- (BLM-) induced lung fibrosis in animal models. However, its mechanism of action remains unknown. We investigated whether roflumilast N-oxide (RNO), the active metabolite of roflumilast, can modulate in vitro the oxidative effects of BLM on human lung fibroblasts (HLF). In addition, since BLM increases the production of F2-isoprostanes that have per se fibrogenic activity, the effect of RNO on oxidative stress and fibrogenesis induced by the F2-isoprostane 8-epi-PGF2α was investigated. HLF were preincubated either with the vehicle or with RNO and exposed to either BLM or 8-epi-PGF2α. Proliferation and collagen synthesis were assessed as [3H]-thymidine and [3H]-proline incorporation. Reactive oxygen species (ROS) and F2-isoprostanes were measured. NADPH oxidase 4 (NOX4) protein and mRNA were also evaluated. BLM increased both cell proliferation and collagen synthesis and enhanced ROS and F2-isoprostane production. These effects were significantly prevented by RNO. Also, RNO significantly reduced the increase in both NOX4 mRNA and protein, induced by BLM. Finally, 8-epi-PGF2α per se stimulated HLF proliferation, collagen synthesis, and NOX4 expression and ROS generation, and RNO prevented these effects. Thus, the antifibrotic effect of RNO observed in vivo may be related to its ability to mitigate ROS generation via downregulation of NOX4

Docker experience at INFN-Pisa Grid Data Center

Clouds and virtualization offer typical answers to the needs of large-scale computing centers to satisfy diverse sets of user communities in terms of architecture, OS, etc. On the other hand, solutions like Docker seems to emerge as a way to rely on Linux kernel capabilities to package only the applications and the development environment needed by the users, thus solving several resource management issues related to cloud-like solutions. In this paper, we present an exploratory (though well advanced) test done at a major Italian Tier2, at INFN-Pisa, where a considerable fraction of the resources and services has been moved to Docker. The results obtained are definitely encouraging, and Pisa is transitioning all of its Worker Nodes and services to Docker containers. Work is currently being expanded into the preparation of suitable images for a completely virtualized Tier2, with no dependency on local configurations

F2-isoprostanes can mediate bleomycin-induced lung fibrosis

F2-isoprostanes (F2-IsoPs) have been considered markers of oxidative stress in various pulmonary diseases, but little is known about their possible role in pulmonary fibrosis. In this study, we have investigated the potential key role of F2-IsoPs as markers and mediators of bleomycin (BLM)-induced pulmonary fibrosis in rats. During the in vivo study, plasma F2-IsoPs showed a peak at 7 days and remained elevated for the entire experimental period. Lung F2-IsoP content nearly tripled 7 days following the intratracheal instillation of BLM, and by 28 days, the value increased about fivefold compared to the controls. Collagen deposition correlated with F2-IsoP content in the lung. Furthermore, from day 21 onwards, lung sections from BLM-treated animals showed α-smooth muscle actin (α-SMA) positive cells, which were mostly evident at 28 days. In vitro studies performed in rat lung fibroblasts (RLF) demonstrated that either BLM or F2-IsoPs stimulated both cell proliferation and collagen synthesis. Moreover, RLF treated with F2-IsoPs showed a significant increase of α-SMA expression compared to control, indicating that F2-IsoPs can readily activate fibroblasts to myofibroblasts. Our data demonstrated that F2-IsoPs can be mediators of key events for the onset and development of lung fibrosis, such as cell proliferation, collagen synthesis and fibroblast activation. Immunocytochemistry analysis, inhibition and binding studies demonstrated the presence of the thromboxane A2 receptor (TP receptor) on lung fibroblasts and suggested that the observed effects may be elicited through the binding to this receptor. Our data added a new perspective on the role of F2-IsoPs in lung fibrosis by providing evidence of a profibrotic role for these mediators in the pathogenesis of pulmonary fibrosis

High availability using virtualization - 3RC

High availability has always been one of the main problems for a data center. Till now high availability was achieved by host per host redundancy, a highly expensive method in terms of hardware and human costs. A new approach to the problem can be offered by virtualization. Using virtualization, it is possible to achieve a redundancy system for all the services running on a data center. This new approach to high availability allows the running virtual machines to be distributed over a small number of servers, by exploiting the features of the virtualization layer: start, stop and move virtual machines between physical hosts. The 3RC system is based on a finite state machine, providing the possibility to restart each virtual machine over any physical host, or reinstall it from scratch. A complete infrastructure has been developed to install operating system and middleware in a few minutes. To virtualize the main servers of a data center, a new procedure has been developed to migrate physical to virtual hosts. The whole Grid data center SNS-PISA is running at the moment in virtual environment under the high availability system.Comment: 10 page

HPC on the Grid: The Theophys Experience

n/

Raising awareness on gender issues: A path through physics, outreach and diversity.

When and where it is convenient to start working on raising awareness on gender issues? Our answer is that high school is definitely a good start, mainly if we think that outreach activities can have a role in the transition to an environment for learning, teaching and researching in physics that is equally attractive and supportive to all genders, at each stage of their education and career path. As researchers of INFN and CNR we promoted a school competition devoted to consider the role of women in science and particularly in Physics. Outreach activities can have the role of raising awareness, knowledge through an active involvement of students for changing the culture and removing stereotypes. In these years we organized 3 contests, with 226 videos, more than 100 high schools and a thousand of students involved. The idea was to try to understand the thinking and knowledge of young people on present and past gender issues connected to women and science, to know how they imagine the society of the future, to understand if they are unaware "carriers" of stereotypes and prejudices and if the cultural change can start from/with them. The students have been asked to produce a video on subjects regarding these questions. The article describes the contests, the evaluation process, the results of first analysis. The work started inside the EU-funded GENERA project, to which both research groups belong, and continues inside the GENERA Network. The collaboration among physicists and sociologists has been, and still is, fundamental in these years

The HPC testbed of the Italian grid infrastructure

n/

ARIANNA: A research environment for neuroimaging studies in autism spectrum disorders

The complexity and heterogeneity of Autism Spectrum Disorders (ASD) require the implementation of dedicated analysis techniques to obtain the maximum from the interrelationship among many variables that describe affected individuals, spanning from clinical phenotypic characterization and genetic profile to structural and functional brain images. The ARIANNA project has developed a collaborative interdisciplinary research environment that is easily accessible to the community of researchers working on ASD (https://arianna.pi.infn.it). The main goals of the project are: to analyze neuroimaging data acquired in multiple sites with multivariate approaches based on machine learning; to detect structural and functional brain characteristics that allow the distinguishing of individuals with ASD from control subjects; to identify neuroimaging-based criteria to stratify the population with ASD to support the future development of personalized treatments. Secure data handling and storage are guaranteed within the project, as well as the access to fast grid/cloud-based computational resources. This paper outlines the web-based architecture, the computing infrastructure and the collaborative analysis workflows at the basis of the ARIANNA interdisciplinary working environment. It also demonstrates the full functionality of the research platform. The availability of this innovative working environment for analyzing clinical and neuroimaging information of individuals with ASD is expected to support researchers in disentangling complex data thus facilitating their interpretation

The ASIMOV Prize for scientific publishing - HEP researchers trigger young people toward science

This work presents the ASIMOV Prize for scientific publishing, which was launched in Italy in 2016. The prize aims to bring the young generations closer to scientific culture, through the critical reading of popular science books. The books are selected by a committee that includes scientists, professors, Ph.D. and Ph.D. students, writers, journalists and friends of culture, and most importantly, over 800 school teachers. Students are actively involved in the prize, according to the best practices of public engagement: they read, review the books and vote for them, choosing the winner. The experience is quite successful: 12,000 students from 270 schools all over Italy participated in the last edition. The possibility of replicating this experience in other countries is indicated, as was done in Brazil in 2020 with more than encouraging results