Contribution of LTi and TH17 cells to B cell aggregate formation in the central nervous system in a mouse model of multiple sclerosis

Background In a subgroup of patients suffering from progressive multiple sclerosis (MS), which is an inflammation-mediated neurodegenerative disease of the central nervous system (CNS), B cell aggregates were discovered within the meninges. Occurrence of these structures was associated with a more severe disease course and cortical histopathology. We have developed the B cell-dependent MP4-induced experimental autoimmune encephalomyelitis (EAE) as a mouse model to mimic this trait of the human disease. The aim of this study was to determine a potential role of lymphoid tissue inducer (LTi) and TH17 cells in the process of B cell aggregate formation in the MP4 model. Methods We performed flow cytometry of cerebellar and splenic tissue of MP4-immunized mice in the acute and chronic stage of the disease to analyze the presence of CD3−CD5−CD4+RORγt+ LTi and CD3+CD5+CD4+RORγt+ TH17 cells. Myelin oligodendrocyte glycoprotein (MOG):35–55-induced EAE was used as B cell-independent control model. We further determined the gene expression profile of B cell aggregates using laser capture microdissection, followed by RNA sequencing. Results While we were able to detect LTi cells in the embryonic spleen and adult intestine, which served as positive controls, there was no evidence for the existence of such a population in acute or chronic EAE in neither of the two models. Yet, we detected CD3−CD5−CD4−RORγt+ innate lymphoid cells (ILCs) and TH17 cells in the CNS, the latter especially in the chronic stage of MP4-induced EAE. Moreover, we observed a unique gene signature in CNS B cell aggregates compared to draining lymph nodes of MP4-immunized mice and to cerebellum as well as draining lymph nodes of mice with MOG:35–55-induced EAE. Conclusion The absence of LTi cells in the cerebellum suggests that other cells might take over the function as an initiator of lymphoid tissue formation in the CNS. Overall, the development of ectopic lymphoid organs is a complex process based on an interplay between several molecules and signals. Here, we propose some potential candidates, which might be involved in the formation of B cell aggregates in the CNS of MP4-immunized mice

A compact Time-Of-Flight detector for space applications: The LIDAL system

Abstract LIDAL (Light Ion Detector for ALTEA system) is a compact detector designed to upgrade ALTEA (Anomalous Long Term Effects on Astronauts) silicon detector apparatus, in order to study in detail the low-Z part of ions spectrum inside the International Space Station (ISS) and to enhance the Particle Identification (PID) capability of the system. The new detector is designed to trigger ALTEA and to perform Time-Of-Flight measurements. It is based on plastic scintillators for fast timing applications read by Photo-Multiplier-Tubes (PMTs). A custom Front End Electronics (FEE) has been designed to reach time resolutions less than 100 ps ( σ ) for protons. A LIDAL prototype has been developed at the University of Rome Tor Vergata to test the timing performance of the scintillators, the PMTs and of the custom FEE using the proton beam line at the TIFPA (Trento Institute for Fundamentals Physics Applications) center in Trento, Italy. The results of these tests are reported and discussed. They have also been used for a preliminary evaluation of the Particle Identification (PID) capability of the final LIDAL-ALTEA detector system in response to the ions spectra expected on-board the ISS

A hybrid multi-particle approach to range assessment-based treatment verification in particle therapy

Particle therapy (PT) used for cancer treatment can spare healthy tissue and reduce treatment toxicity. However, full exploitation of the dosimetric advantages of PT is not yet possible due to range uncertainties, warranting development of range-monitoring techniques. This study proposes a novel range-monitoring technique introducing the yet unexplored concept of simultaneous detection and imaging of fast neutrons and prompt-gamma rays produced in beam-tissue interactions. A quasimonolithic organic detector array is proposed, and its feasibility for detecting range shifts in the context of proton therapy is explored through Monte Carlo simulations of realistic patient models and detector resolution efects. The results indicate that range shifts of 1 mm can be detected at relatively low proton intensities (22.30(13) × 107 protons/spot) when spatial information obtained through imaging of both particle species are used simultaneously. This study lays the foundation for multiparticle detection and imaging systems in the context of range verifcation in PTpublishedVersio

Sustainable Innovation in a Multi-University Master Course

Mobility, multi-locality, and transnational migration are current social developments among the population of the European Union. These social developments in society and companies, linked to the challenges of sustainability, lead to new requirements for working in the European Union. Teaching and learning in higher education needs to adapt to these requirements. As a result, new and innovative teaching and learning practices in higher education should provide competencies for transnational teamwork in the curriculum of tomorrow's engineers in order to ensure their competitiveness in the job market and advantage in their future careers. Thirteen European students from four countries participated in a new project-based course, called the "European Engineering Team". Students focused on the development of two innovative and sustainable products. The goal of this paper is to present the thermal pallet cover, which is the result of the first one-year transnational and sustainability-oriented project. This paper also aims to present the process of performing the project. It provides the overview and discussion of engineering and management tasks that students completed in the transnational environment, working remotely at their own campuses between scheduled transnational meetings. The work contributes to project-oriented learning that may constitute a basis for teaching holistic engineering courses at mechanical and industrial engineering departments