are we able to harness the immunomodulatory power of cytokines for novel autoimmune disease treatments

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FLASH radiotherapy with electrons: issues related to the production, monitoring, and dosimetric characterization of the beam

Various in vivo experimental works carried out on different animals and organs have shown that it is possible to reduce the damage caused to healthy tissue still preserving the therapeutic efficacy on the tumor tissue, by drastically reducing the total time of dose delivery (<200 ms). This effect, called the FLASH effect, immediately attracted considerable attention within the radiotherapy community, due to the possibility of widening the therapeutic window and treating effectively tumors which appear radioresistant to conventional techniques. Despite the experimental evidence, the radiobiological mechanisms underlying the FLASH effect and the beam parameters contributing to its optimization are not yet known in details. In order to fully understand the FLASH effect, it might be worthy to investigate some alternatives which can further improve the tools adopted so far, in terms of both linac technology and dosimetric systems. This work investigates the problems and solutions concerning the realization of an electron accelerator dedicated to FLASH therapy and optimized for in vivo experiments. Moreover, the work discusses the saturation problems of the most common radiotherapy dosimeters when used in the very high dose-per-pulse FLASH conditions and provides some preliminary experimental data on their behavior

Bacteriophage therapy to reduce colonization of campylobacter jejuni in broiler chickens before slaughter

Campylobacteriosis is the most commonly reported gastrointestinal disease in humans. Campybacter jejuni is the main cause of the infection, and bacterial colonization in broiler chickens is widespread and difficult to prevent, leading to high risk of occurrence in broiler meat. Phage therapy represents an alternative strategy to control Campylobacter in poultry. The aim of this work was to assess the efficacy of two field-isolated bacteriophages against experimental infections with an anti-microbial resistant (AMR) Campylobacter jejuni strain. A two-step phage application was tested according to a specific combination between chickens’ rearing time and specific multiplicities of infections (MOIs), in order to reduce the Campylobacter load in the animals at slaughtering and to limit the development of phage-resistant mutants. In particular, 75 broilers were divided into three groups (A, B and C), and phages were administered to animals of groups B and C at day 38 (Φ 16-izsam) and 39 (Φ 7-izsam) at MOI 0.1 (group B) and 1 (group C). All broilers were euthanized at day 40, and Campylobacter jejuni was enumerated in cecal contents. Reductions in Campylobacter counts were statistically significant in both group B (1 log10 colony forming units (cfu)/gram (gr)) and group C (2 log10 cfu/gr), compared to the control group. Our findings provide evidence about the ability of phage therapy to reduce the Campylobacter load in poultry before slaughtering, also associated with anti-microbial resistance pattern

Pregnane-X-receptor mediates the anti-inflammatory activities of rifaximin on detoxification pathways in intestinal epithelial cells

International audienceThe pregnane-X-receptor (PXR) is master gene overseeing detoxification of wide number of xenobiotics and is critical for maintenance of intestinal integrity. The intestinal expression of genes involved in cellular detoxification is down-regulated in patients with inflammatory bowel diseases (IBD). Rifaximin, is a non absorbable antibiotic endowed with a PXR agonistic activity. In the present study we have investigated whether rifaximin activates PXR in primary human colon epithelial cells and human colon biopsies and assessed whether this antibiotic antagonizes the effect of Tumor necrosis factor (TNF)-α on expression of PXR and PXR-related genes. Present results demonstrate that primary colon epithelial cells express PXR and that their exposure to rifaximin induces the expression of genes involved in cellular detoxification. Exposure to TNFα reduces the expression of PXR mRNA as well as expression of its target genes. This inhibitory effect was prevented by that co-treatment with rifaximin. Knocking down the expression of PXR in colon epithelial cells by an anti-PXR siRNA, abrogated the counter-regulatory effects exerted by rifaximin on cell exposed to TNFα. Finally, exposure of colon biopsies obtained from ulcerative colitis patients to rifaximin increased the expression of genes involved in xenobiotics metabolism. In aggregate, these data illustrate that rifaximin increases the expression of PXR and PXR-regulated genes involved in the metabolism and excretion of xenobiotics and antagonized the effects of TNFα in intertsinal epithelial cells and colon biopsies. These non-antibiotic effects of rifaximin could contribute to the maintenance of the intestinal barrier integrity against xenobiotics and products generated by luminal bacteria

Conceptual Design of a Soft X‐ray SASE‐FEL Source

FELs based on SASE are believed to be powerful tools to explore the frontiers of basic sciences, from physics to chemistry to biology. Intense R&D programs have started in the USA and Europe in order to understand the SASE physics and to prove the feasibility of these sources. The allocation of considerable resources in the Italian National Research Plan (PNR) brought about the formation of a CNR‐ENEA‐INFN‐University of Roma "Tor Vergata" study group. A conceptual design study has been developed and possible schemes for linac sources have been investigated, bringing to the SPARX proposal. We report in this paper the results of a preliminary start to end simulation concerning one option we are considering based on an S‐band normal conducting linac with high brightness photoinjector integrated in a RF compressor

A four-dimensional Vlasov solver for microbunching instability in the injection system for X-ray FELs

The micro-bunching instability (MBI) is seeded by small charge-density fluctuations in the electron bunches, and is successively amplified by the combined effect of space charge and coherent synchrotron radiation, as the beam travels through magnetic compressors. The quantitative understanding of this effect demands for accurate numerical simulations. Here we report on the progress of an upgrading of a 2D Vlasov solver code toward a 4D grid-based Vlasov solver, including also the transversedynamics. The goal is to provide an accurate characterization of the MBI seeded by random noise present in the bunch distribution. We also comment on the advantages of our procedure with respect to other approaches, e.g. macroparticle simulations

Laguerre polynomials and Tricomi functions

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7 , Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal