Negative ion Time Projection Chamber operation with SF6_{6} at nearly atmospheric pressure

We present measurements of drift velocities and mobilities of some innovative negative ion gas mixtures at nearly atmospheric pressure based on SF$_{6}$ as electronegative capture agent and of pure SF$_{6}$ at various pressures, performed with the NITEC detector. NITEC is a Time Projection Chamber with 5 cm drift distance readout by a GEMPix, a triple thin GEMs coupled to a Quad-Timepix chip, directly sensitive to the deposited charge on each of the 55 $\times$ 55 $\mu$m$^2$ pixel. Our results contribute to expanding the knowledge on the innovative use of SF$_{6}$ as negative ion gas and extend to triple thin GEMs the possibility of negative ion operation for the first time. Above all, our findings show the feasibility of negative ion operation with He:CF$_4$:SF$_{6}$ at 610 Torr, opening extremely interesting possibility for next generation directional Dark Matter detectors at 1 bar

Targeting RAGE prevents muscle wasting and prolongs survival in cancer cachexia

Background: Cachexia, a multifactorial syndrome affecting more than 50% of patients with advanced cancer and responsible for ~20% of cancer-associated deaths, is still a poorly understood process without a standard cure available. Skeletal muscle atrophy caused by systemic inflammation is a major clinical feature of cachexia, leading to weight loss, dampening patients' quality of life, and reducing patients' response to anticancer therapy. RAGE (receptor for advanced glycation end-products) is a multiligand receptor of the immunoglobulin superfamily and a mediator of muscle regeneration, inflammation, and cancer. Methods: By using murine models consisting in the injection of colon 26 murine adenocarcinoma (C26-ADK) or Lewis lung carcinoma (LLC) cells in BALB/c and C57BL/6 or Ager−/− (RAGE-null) mice, respectively, we investigated the involvement of RAGE signalling in the main features of cancer cachexia, including the inflammatory state. In vitro experiments were performed using myotubes derived from C2C12 myoblasts or primary myoblasts isolated from C57BL/6 wild type and Ager−/− mice treated with the RAGE ligand, S100B (S100 calcium-binding protein B), TNF (tumor necrosis factor)α±IFN (interferon) γ, and tumour cell- or masses-conditioned media to analyse hallmarks of muscle atrophy. Finally, muscles of wild type and Ager−/− mice were injected with TNFα/IFNγ or S100B in a tumour-free environment. Results: We demonstrate that RAGE is determinant to activate signalling pathways leading to muscle protein degradation in the presence of proinflammatory cytokines and/or tumour-derived cachexia-inducing factors. We identify the RAGE ligand, S100B, as a novel factor able to induce muscle atrophy per se via a p38 MAPK (p38 mitogen-activated protein kinase)/myogenin axis and STAT3 (signal transducer and activator of transcription 3)-dependent MyoD (myoblast determination protein 1) degradation. Lastly, we found that in cancer conditions, an increase in serum levels of tumour-derived S100B and HMGB1 (high mobility group box 1) occurs leading to chronic activation/overexpression of RAGE, which induces hallmarks of cancer cachexia (i.e. muscle wasting, systemic inflammation, and release of tumour-derived pro-cachectic factors). Absence of RAGE in mice translates into reduced serum levels of cachexia-inducing factors, delayed loss of muscle mass and strength, reduced tumour progression, and increased survival. Conclusions: RAGE is a molecular determinant in inducing the hallmarks of cancer cachexia, and molecular targeting of RAGE might represent a therapeutic strategy to prevent or counteract the cachectic syndrome

Drivers involved in road traffic accidents in Piedmont Region: psychoactive substances consumption

Introduction. The role played by psychoactive substances in road safety has become object of increasing interest: these substances can reduce driving performance and increase accidents risk. Aims of the study are to establish the dimension of the problem and to describe the characteristics of people involved in accidents under psychoactive substance effects. Methods. Target population consists of people from 18 to 60 years old involved in accidents afferent in Emergency Rooms. Subjects were interviewed by surveyors and a urines was collected for psychoactive substances screening. Results. In 18.5% of people we found substance consumption. Cocaine was the most frequently detected substance (9.5%), then benzodiazepines (7.5%), methadone, morphine and marijuana (THC) (3.5%). In 5.5% of subjects more then one substance was found. Considering only illegal substances detected, female have a higher risk to be consumers (OR = 1.36) and the young age (18-35 years) seems to be at higher prevalence and risk for substance use (OR = 1.86). Discussion. Considering all psychoactive substances detected, clearly the problem about substances consumption and driving is not restricted to youngest but involves all age groups. Conclusions. In order to decrease the number of accidents due to substance use, new prevention programmes able to involve also middle age groups should be planned

Present results and perspectives of allogeneic non-myeloablative hematopoietic stem cell transplantation for treatment of human solid tumors

Several clinical observations have confirmed that a donor immune-mediated anti-malignancy effect, called graft-versus-leukemia or graft-versus-tumor, occurs following allogeneic hematopoietic stem cell transplantation. While the potential antitumor effect mediated by donor lymphocytes has been established in many hematological malignancies, its efficacy in inducing clinically meaningful responses in solid tumors has been largely unexplored despite evidence of its potential benefit in experimental animal models. Only in recent years has the investigational application of non-myeloablative stem cell transplantation in patients with refractory non-hematological cancers proved that a graft-versus-tumor effect can be generated in patients with metastatic renal cell cancer and possibly with other solid tumors. In the present article we review the biological basis, development and early clinical results of this novel immunotherapeutic approach for solid tumors

Performance of Optically Readout GEM-based TPC with a 55Fe source

Optical readout of large Time Projection Chambers (TPCs) with multiple Gas Electron Multipliers (GEMs) amplification stages has shown to provide very interesting performances for high energy particle tracking. Proposed applications for low-energy and rare event studies, such as Dark Matter search, ask for demanding performance in the keV energy range. The performance of such a readout was studied in details as a function of the electric field configuration and GEM gain by using a $^{55}$Fe source within a 7 litre sensitive volume detector developed as a part of the R\&D for the CYGNUS project. Results reported in this paper show that the low noise level of the sensor allows to operate with a 2~keV threshold while keeping a rate of fake-events lesser than 10 per year. In this configuration, a detection efficiency well above 95\% along with an energy resolution ($\sigma$) of 18\% is obtained for the 5.9 keV photons, demonstrating the very promising capabilities of this technique

MPGD Optical Read Out for Directional Dark Matter Search

The Time Projection method is an ideal candidate to track low energy release particles. Large volumes can be readout by means of a moderate number of channels providing a complete 3D reconstruction of the charged tracks within the sensitive volume. It allows the measurement not only of the total released energy but also of the energy release density along the tracks that can be very useful for particle identification and to solve the head-tail ambiguity of the tracks. Moreover, gas represents a very interesting target to study Dark Matter interactions. In gas, nuclear recoils can travel enough to give rise to tracks long enough to be acquired and reconstructed

A photogrammetric method for target monitoring inside the MEG II detector

An automatic target monitoring method based on photographs taken by a CMOS photo-camera has been developed for the MEG II detector. The technique could be adapted for other fixed-target experiments requiring good knowledge of their target position to avoid biases and systematic errors in measuring the trajectories of the outcoming particles. A CMOS-based, high resolution, high radiation tolerant, and high magnetic field resistant photo-camera was mounted inside the MEG II detector at the Paul Scherrer Institute (Switzerland). MEG II is used to search for lepton flavor violation in muon decays. The photogrammetric method’s challenges, affecting measurements of low momentum particles’ tracks, are the high magnetic field of the spectrometer, high radiation levels, tight space constraints, and the need to limit the material budget in the tracking volume. The camera is focused on the dot pattern drawn on the thin MEG II target, about 1 m away from the detector endcaps where the photo-camera is placed. Target movements and deformations are monitored by comparing images of the dots taken at various times during the measurement. The images are acquired with a Raspberry board and analyzed using custom software. Global alignment to the spectrometer is guaranteed by corner cubes placed on the target support. As a result, the target monitoring fulfills the needs of the experiment