Muon Radiography Investigations in Boreholes with a Newly Designed Cylindrical Detector

Muons are constantly produced in cosmic-rays and reach the Earth surface with a flux of about 160 particles per second per square meter. The abundance of muons with respect to other cosmic particles and their capability to cross dense materials with low absorption rate allow them to be exploited for large scale geological or human-made object imaging. Muon radiography is based on similar principles as X-ray radiography, measuring the surviving rate of muons escaping the target and relating it to the mass distribution inside the object. In the course of decades, after the first application in 1955, the methodology has been applied in several different fields. Muography allows us to measure the internal density distribution of the investigated object, or to simply highlight the presence of void regions by observing any excess of muons. Most of these applications require the detector to be installed below the rock being probed. In case that possible installation sites are not easily accessible by people, common instrumentation cannot be installed. A novel borehole cylindrical detector for muon radiography has been recently developed to deal with these conditions. It has been realized with a cylindrical geometry to fit typical borehole dimensions. Its design maximizes the geometrical acceptance, minimizing the dead spaces by the use of arc-shaped scintillators. The details of the construction and preliminary results of the first usage are described in this paper. © 2022 by the authors

A new cylindrical borehole detector for radiographic imaging with muons

Muon radiography is a methodology which enables measuring the mass distribution within large objects. It exploits the abundant flux of cosmic muons and uses detectors with different technologies depending on the application. As the sensitive surface and geometric acceptance are two fundamental parameters for increasing the collection of muons, the optimization of the detectors is very significant. Here we show a potentially innovative detector of size and shape suitable to be inserted inside a borehole, that optimizes the sensitive area and maximizes the angular acceptance thanks to its cylindrical geometry obtained using plastic arc-shaped scintillators. Good spatial resolution is obtained with a reasonable number of channels. The dimensions of the detector make it ideal for use in 25 cm diameter wells. Detailed simulations based on Monte Carlo methods show great cavity detection capability. The detector has been tested in the laboratory, achieving overall excellent performance

CHANTI: a Fast and Efficient Charged Particle Veto Detector for the NA62 Experiment at CERN

The design, construction and test of a charged particle detector made of scintillation counters read by Silicon Photomultipliers (SiPM) is described. The detector, which operates in vacuum and is used as a veto counter in the NA62 experiment at CERN, has a single channel time resolution of 1.14 ns, a spatial resolution of ~2.5 mm and an efficiency very close to 1 for penetrating charged particles

The Natural Compound Fucoidan From New Zealand Undaria Pinnatifida Synergizes With the ERBB Inhibitor Lapatinib Enhancing Melanoma Growth Inhibition

Melanoma remains one of the most aggressive and therapy-resistant cancers. Finding new treatments to improve patient outcomes is an ongoing effort. We previously demonstrated that melanoma relies on the activation of ERBB signaling, specifically of the ERBB3/ERBB2 cascade. Here we show that melanoma tumor growth is inhibited by 60% over controls when treated with lapatinib, a clinically approved inhibitor of ERBB2/EGFR. Importantly, tumor growth is further inhibited to 85% when the natural compound fucoidan from New Zealand U. pinnatifida is integrated into the treatment regimen. Fucoidan not only enhances tumor growth inhibition, it counteracts the morbidity associated with prolonged lapatinib treatment. Fucoidan doubles the cell killing capacity of lapatinib. These effects are associated with a further decrease in AKT and NFκB signaling, two key pathways involved in melanoma cell survival. Importantly, the enhancing cell killing effects of fucoidan can be recapitulated by inhibiting ERBB3 by either a specific shRNA or a novel, selective ERBB3 neutralizing antibody, reiterating the key roles played by this receptor in melanoma. We therefore propose the use of lapatinib or specific ERBB inhibitors, in combination with fucoidan as a new treatment of melanoma that potentiates the effects of the inhibitors while protecting from their potential side effects

MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration

Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs down-regulation is a hallmark of malignant transformation. In the present report, we showed that the miR-128-3p, which is up-regulated in lung cancer tissues, has Drosha and Dicer, two key enzymes of miRNAs processing, as the main modulation targets leading to the widespread down-regulation of miRNA expression. We observed that the miRNAs downregulation induced by miR-128-3p contributed to the tumorigenic properties of lung cancer cells. In particular, miR- 128-3p-mediated miRNAs down-regulation contributed to aberrant SNAIL and ZEB1 expression thereby promoting the epithelial-to-mesenchymal transition (EMT) program. Drosha also resulted to be implicated in the control of migratory phenotype as its expression counteracted miR-128-3p functional effects. Our study provides mechanistic insights into the function of miR-128-3p as a key regulator of the malignant phenotype of lung cancer cells. This also enforces the remarkable impact of Drosha and Dicer alteration in cancer, and in particular it highlights a role for Drosha in non-smallcell lung cancer cells migration

COVID-eVax, an electroporated DNA vaccine candidate encoding the SARS-CoV-2 RBD, elicits protective responses in animal models

The COVID-19 pandemic caused by SARS-CoV-2 has made the development of safe and effective vaccines a critical priority. To date, four vaccines have been approved by European and American authorities for preventing COVID-19, but the development of additional vaccine platforms with improved supply and logistics profiles remains a pressing need. Here we report the preclinical evaluation of a novel COVID-19 vaccine candidate based on the electroporation of engineered, synthetic cDNA encoding a viral antigen in the skeletal muscle. We constructed a set of prototype DNA vaccines expressing various forms of the SARS-CoV-2 spike (S) protein and assessed their immunogenicity in animal models. Among them, COVID-eVax—a DNA plasmid encoding a secreted monomeric form of SARS-CoV-2 S protein receptor-binding domain (RBD)—induced the most potent anti-SARS-CoV-2 neutralizing antibody responses (including against the current most common variants of concern) and a robust T cell response. Upon challenge with SARS-CoV-2, immunized K18-hACE2 transgenic mice showed reduced weight loss, improved pulmonary function, and lower viral replication in the lungs and brain. COVID-eVax conferred significant protection to ferrets upon SARS-CoV-2 challenge. In summary, this study identifies COVID-eVax as an ideal COVID-19 vaccine candidate suitable for clinical development. Accordingly, a combined phase I-II trial has recently started

Highly specific memory b cells generation after the 2nd dose of bnt162b2 vaccine compensate for the decline of serum antibodies and absence of mucosal iga

Specific memory B cells and antibodies are a reliable read-out of vaccine efficacy. We analysed these biomarkers after one and two doses of BNT162b2 vaccine. The second dose significantly increases the level of highly specific memory B cells and antibodies. Two months after the second dose, specific antibody levels decline, but highly specific memory B cells continue to increase, thus predicting a sustained protection from COVID-19. We show that although mucosal IgA is not induced by the vaccination, memory B cells migrate in response to inflammation and secrete IgA at mucosal sites. We show that the first vaccine dose may lead to an insufficient number of highly specific memory B cells and low concentration of serum antibodies, thus leaving vaccinees without the immune robustness needed to ensure viral elimination and herd immunity. We also clarify that the reduction of serum antibodies does not diminish the force and duration of the immune protection induced by vaccination. The vaccine does not induce sterilizing immunity. Infection after vaccination may be caused by the lack of local preventive immunity because of the absence of mucosal IgA

Construction techniques and performances of a full size prototype Micromegas chamber for the ATLAS muon spectrometer upgrade

A full scale prototype of a Micromegas precision tracking chamber for the upgrade of the ATLAS detector at the LHC Collider has been built between October 2015 and April 2016. This paper describes in detail the procedures used in constructing the single modules of the chamber in various INFN laboratories and the final assembly at the Frascati National Laboratories (LNF). Results of the chamber exposure to the CERN H8 beam line in June 2016 are also presented. The performances achieved in the construction and the results of the test beam are compared with the requirements, which are imposed by the severe environment during the data-taking of the LHC foreseen for the next years

Prospects for combined analyses of hadronic emission from γ\gamma-ray sources in the Milky Way with CTA and KM3NeT

The Cherenkov Telescope Array and the KM3NeT neutrino telescopes are major upcoming facilities in the fields of $\gamma$-ray and neutrino astronomy, respectively. Possible simultaneous production of $\gamma$ rays and neutrinos in astrophysical accelerators of cosmic-ray nuclei motivates a combination of their data. We assess the potential of a combined analysis of CTA and KM3NeT data to determine the contribution of hadronic emission processes in known Galactic $\gamma$-ray emitters, comparing this result to the cases of two separate analyses. In doing so, we demonstrate the capability of Gammapy, an open-source software package for the analysis of $\gamma$-ray data, to also process data from neutrino telescopes. For a selection of prototypical $\gamma$-ray sources within our Galaxy, we obtain models for primary proton and electron spectra in the hadronic and leptonic emission scenario, respectively, by fitting published $\gamma$-ray spectra. Using these models and instrument response functions for both detectors, we employ the Gammapy package to generate pseudo data sets, where we assume 200 hours of CTA observations and 10 years of KM3NeT detector operation. We then apply a three-dimensional binned likelihood analysis to these data sets, separately for each instrument and jointly for both. We find that the largest benefit of the combined analysis lies in the possibility of a consistent modelling of the $\gamma$-ray and neutrino emission. Assuming a purely leptonic scenario as input, we obtain, for the most favourable source, an average expected 68% credible interval that constrains the contribution of hadronic processes to the observed $\gamma$-ray emission to below 15%.Comment: 18 pages, 15 figures. Submitted to journa

Persistent B cell memory after SARS-CoV-2 vaccination is functional during breakthrough infections

Breakthrough SARS-CoV-2 infections in fully vaccinated individuals are considered a consequence of waning immunity. Serum antibodies represent the most measurable outcome of vaccine-induced B cell memory. When antibodies decline, memory B cells are expected to persist and perform their function, preventing clinical disease. We investigated whether BNT162b2 mRNA vaccine induces durable and functional B cell memory in vivo against SARS-CoV-2 3, 6, and 9 months after the second dose in a cohort of health care workers (HCWs). While we observed physiological decline of SARS-CoV-2-specific antibodies, memory B cells persist and increase until 9 months after immunization. HCWs with breakthrough infections had no signs of waning immunity. In 3–4 days, memory B cells responded to SARS-CoV-2 infection by producing high levels of specific antibodies in the serum and anti-Spike IgA in the saliva. Antibodies to the viral nucleoprotein were produced with the slow kinetics typical of the response to a novel antigen