IL-18 receptor marks functional CD8+ T cells in non-small cell lung cancer

IL-18 is an inflammasome-related cytokine, member of the IL-1 family, produced by a wide range of cells in response to signals by several pathogen-or damage-associated molecular patterns. It can be highly represented in tumor patients, but its relevance in human cancer development is not clear. In this study, we provide evidence that IL-18 is principally expressed in tumor cells and, in concert with other conventional Th1 cell-driven cytokines, has a pivotal role in establishing a pro-inflammatory milieu in the tumor microenvironment of human non-small cell lung cancer (NSCLC). Interestingly, the analysis of tumor-infiltrating CD8(+) T cell populations showed that (i) the relative IL-18 receptor (IL-18R) is significantly more expressed by the minority of cells with a functional phenotype (T-bet(+)Eomes(+)), than by the majority of those with the dysfunctional phenotype T-bet(+)Eomes(+) generally resident within tumors; (ii) as a consequence, the former are significantly more responsive than the latter to IL-18 stimulus in terms of IFN gamma production ex vivo; (iii) PD-1 expression does not discriminate these two populations. These data indicate that IL-18R may represent a biomarker of the minority of functional tumor-infiltrating CD8(+) T cells in adenocarcinoma NSCLC patients. In addition, our results lead to envisage the possible therapeutic usage of IL-18 in NSCLC, even in combination with other checkpoint inhibitor approaches

Design of a plasma discharge circuit for particle wakefield acceleration

Plasma wakefield acceleration is the most promising acceleration technique known nowadays, able to provide very high accelerating fields (10–100 GV m 1), enabling acceleration of electrons to GeV energy in few centimetres. However, the quality of the electron bunches accelerated with this technique is still not comparable with that of conventional accelerators; radiofrequency-based accelerators, in fact, are limited in the accelerating field (10–100 MV m 1) requiring therefore kilometric distances to reach the GeV energies, but can provide very bright electron bunches. Combining high brightness electron bunches from conventional accelerators and high accelerating fields reachable with plasmas could be a good compromise allowing to further accelerate high brightness electron bunches coming from LINAC while preserving electron beam quality. Following the idea of plasma wave resonant excitation driven by a train of short bunches, we have started to study the requirements in terms of plasma for SPARC-LAB [1,2]. In particular, here we focus on the ionization process; we show a simplified model to study the evolution of plasma induced by discharge, very useful to design the discharge circuit able to fully ionize the gas and bring the plasma at the needed temperature and density

Self-amplified spontaneous emission for a single pass free-electron laser

SPARC (acronym of "Sorgente Pulsata ed Amplificata di Radiazione Coerente", i.e. Pulsed and Amplified Source of Coherent Radiation) is a single pass free-electron laser designed to obtain high gain amplification at a radiation wavelength of 500 nm. Self-amplified spontaneous emission has been observed driving the amplifier with the high-brightness beam of the SPARC linac. We report measurements of energy, spectra, and exponential gain. Experimental results are compared with simulations from several numerical codes

Status of the SPARC-X Project

SPARC-X is a two branch project consisting in the SPARC test facility dedicated to the development and test of critical subsystems such as high brightness photoinjector and a modular expandable undulator for SASE-FEL experiments at 500 nm with seeding, and the SPARX facility aiming at generation of high brilliance coherent radiation in the 1.5-13 nm range, based on the achieved expertise. The projects are supported by MIUR (Research Department of Italian Government) and Regione Lazio. SPARC has completed the commissioning phase of the photoinjector in November 2006. The achieved experimental results are here summarized together with the status of the second phase commissioning plans. The SPARX project is based on the generation of ultra high peak brightness electron beams at the energy of 1 and 2 GeV generating radiation in the 1.5-13 nm range. The construction is at the moment planned in two steps starting with a 1 GeV Linac. The project layout including both RF-compression and magnetic chicane techniques has been studied

Impact of Aetiological Treatment on Conventional and Multiplex Serology in Chronic Chagas Disease

The main criterion for treatment effectiveness in Chagas Disease has been the seronegative conversion of previously reactive serology, generally achieved many years post-treatment. The lack of reliable tests to ensure parasite clearance and to examine the effect of treatment is the main difficulty in evaluating treatment for chronic Chagas disease. Decreases of conventional and non-conventional serological titers can be useful tools to monitor the early impact of treatment. We serially measured changes in antibody levels, including seronegative conversion as well as declines in titers in 53 benznidazole-treated and 89 untreated chronically T. cruzi-infected subjects. Seronegative conversion as well as decreases of titers was significantly higher in treated compared with untreated patients. A strong concordance was found between decreases of titers of conventional and non-conventional serologic tests post-treatment, reaffirming the findings. When seronegative conversion plus decreases of titers were considered altogether, the impact of treatment was higher, in a shorter follow-up period than previously considered. New tools for monitoring the effectiveness of treatment of chronic Chagas disease are necessary, and the results showed in this study is a contribution to researchers and physicians who assist patients suffering from this disease

Overview of the FTU results

Since the 2018 IAEA FEC Conference, FTU operations have been devoted to several experiments covering a large range of topics, from the investigation of the behaviour of a liquid tin limiter to the runaway electrons mitigation and control and to the stabilization of tearing modes by electron cyclotron heating and by pellet injection. Other experiments have involved the spectroscopy of heavy metal ions, the electron density peaking in helium doped plasmas, the electron cyclotron assisted start-up and the electron temperature measurements in high temperature plasmas. The effectiveness of the laser induced breakdown spectroscopy system has been demonstrated and the new capabilities of the runaway electron imaging spectrometry system for in-flight runaways studies have been explored. Finally, a high resolution saddle coil array for MHD analysis and UV and SXR diamond detectors have been successfully tested on different plasma scenarios

Characterization of the Interaction of Full-Length HIV-1 Vif Protein with its Key Regulator CBFβ and CRL5 E3 Ubiquitin Ligase Components

Human immunodeficiency virus-1 (HIV-1) viral infectivity factor (Vif) is essential for viral replication because of its ability to eliminate the host's antiviral response to HIV-1 that is mediated by the APOBEC3 family of cellular cytidine deaminases. Vif targets these proteins, including APOBEC3G, for polyubiquitination and subsequent proteasome-mediated degradation via the formation of a Cullin5-ElonginB/C-based E3 ubiquitin ligase. Determining how the cellular components of this E3 ligase complex interact with Vif is critical to the intelligent design of new antiviral drugs. However, structural studies of Vif, both alone and in complex with cellular partners, have been hampered by an inability to express soluble full-length Vif protein. Here we demonstrate that a newly identified host regulator of Vif, core-binding factor-beta (CBFβ), interacts directly with Vif, including various isoforms and a truncated form of this regulator. In addition, carboxyl-terminal truncations of Vif lacking the BC-box and cullin box motifs were sufficient for CBFβ interaction. Furthermore, association of Vif with CBFβ, alone or in combination with Elongin B/C (EloB/C), greatly increased the solubility of full-length Vif. Finally, a stable complex containing Vif-CBFβ-EloB/C was purified in large quantity and shown to bind purified Cullin5 (Cul5). This efficient strategy for purifying Vif-Cul5-CBFβ-EloB/C complexes will facilitate future structural and biochemical studies of Vif function and may provide the basis for useful screening approaches for identifying novel anti-HIV drug candidates

2 nd Brazilian Consensus on Chagas Disease, 2015

Abstract Chagas disease is a neglected chronic condition with a high burden of morbidity and mortality. It has considerable psychological, social, and economic impacts. The disease represents a significant public health issue in Brazil, with different regional patterns. This document presents the evidence that resulted in the Brazilian Consensus on Chagas Disease. The objective was to review and standardize strategies for diagnosis, treatment, prevention, and control of Chagas disease in the country, based on the available scientific evidence. The consensus is based on the articulation and strategic contribution of renowned Brazilian experts with knowledge and experience on various aspects of the disease. It is the result of a close collaboration between the Brazilian Society of Tropical Medicine and the Ministry of Health. It is hoped that this document will strengthen the development of integrated actions against Chagas disease in the country, focusing on epidemiology, management, comprehensive care (including families and communities), communication, information, education, and research

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