Tri-Resonant Leptogenesis in a Seesaw Extension of the Standard Model

We study a class of leptogenesis models where the light neutrinos acquire their observed small masses by a symmetry-motivated construction. This class of models may naturally include three nearly degenerate heavy Majorana neutrinos that can strongly mix with one another and have mass differences comparable to their decay widths. We find that such a tri-resonant heavy neutrino system can lead to leptonic CP asymmetries which are further enhanced than those obtained in the usual bi-resonant approximation. Moreover, we solve the Boltzmann equations by paying special attention to the temperature dependence of the relativistic degrees of freedom of the plasma. The latter results in significant corrections to the evolution equations for the heavy neutrinos and the lepton asymmetry that have been previously ignored in the literature. We show the importance of these corrections to accurately describe the dynamical evolution of the baryon-to-photon ratio $\eta_B$ for heavy neutrino masses at and below $100$ GeV, and demonstrate that successful leptogenesis at lower masses can be significantly affected by the variation of the relativistic dofs. The parameter space for the leptogenesis model is discussed, and it could be probed in future experimental facilities searching for charged lepton flavour violation and heavy neutrinos in future $Z$-boson factories.Comment: 42 pages, 10 figures, additional references included, inclusion of additional clarifying comments, to appear in JHE

Tri-Resonant Leptogenesis

We present a class of leptogenesis models where the light neutrinos acquire their observed mass through a symmetry-motivated construction. We consider an extension of the Standard Model, which includes three singlet neutrinos which have mass splittings comparable to their decay widths. We show that this tri-resonant structure leads to an appreciable increase in the observed CP asymmetry over that found previously in typical bi-resonant models. To analyse such tri-resonant scenarios, we solve a set of coupled Boltzmann equations, crucially preserving the variations in the relativistic degrees of freedom. We highlight the fact that small variations at high temperatures can have major implications for the evolution of the baryon asymmetry when the singlet neutrino mass scale is below $100$ GeV. We then illustrate how this variation can significantly affect the ability to find successful leptogenesis at these low masses. Finally, the parameter space for viable leptogenesis is delineated, and comparisons are made with current and future experiments.Comment: 16 pages, 5 figures, conference proceedings for Corfu Summer Institute 2022, School and Workshops on Elementary Particle Physics and Gravity, August 28 - September 8, 2022, Corfu, Greec

Integral abutment bridges: Investigation of seismic soil-structure interaction effects by shaking table testing

In recent years there has been renewed interest on integral abutment bridges (IABs), mainly due to their low construction and maintenance cost. Owing to the monolithic connection between deck and abutments, there is strong soil-structure interaction between the bridge and the backfill under both thermal action and earthquake shaking. Although some of the regions where IABs are adopted qualify as highly seismic, there is limited knowledge as to their dynamic behaviour and vulnerability under strong ground shaking. To develop a better understanding on the seismic behaviour of IABs, an extensive experimental campaign involving over 75 shaking table tests and 4800 time histories of recorded data, was carried out at EQUALS Laboratory, University of Bristol, under the auspices of EU-sponsored SERA project (Seismology and Earthquake Engineering Research Infrastructure Alliance for Europe). The tests were conducted on a 5 m long shear stack mounted on a 3 m × 3 m 6-DOF earthquake simulator, focusing on interaction effects between a scaled bridge model, abutments, foundation piles and backfill soil. The study aims at (a) developing new scaling procedures for physical modelling of IABs, (b) investigating experimentally the potential benefits of adding compressible inclusions (CIs) between the abutment and the backfill and (c) exploring the influence of different types of connection between the abutment and the pile foundation. Results indicate that the CI reduces the accelerations on the bridge deck and the settlements in the backfill, while disconnecting piles from the cap decreases bending near the pile head

Monte-Carlo dosimetry on a realistic cell monolayer geometry exposed to alpha particles

The energy and specific energy absorbed in the main cell compartments (nucleus and cytoplasm) in typical radiobiology experiments are usually estimated by calculations as they are not accessible for a direct measurement. In most of the work, the cell geometry is modelled using the combination of simple mathematical volumes. We propose a method based on high resolution confocal imaging and ion beam analysis (IBA) in order to import realistic cell nuclei geometries in Monte-Carlo simulations and thus take into account the variety of different geometries encountered in a typical cell population. Seventy-six cell nuclei have been imaged using confocal microscopy and their chemical composition has been measured using IBA. A cellular phantom was created from these data using the ImageJ image analysis software and imported in the Geant4 Monte-Carlo simulation toolkit. Total energy and specific energy distributions in the 76 cell nuclei have been calculated for two types of irradiation protocols: a 3 MeV alpha particle microbeam used for targeted irradiation and a 239Pu alpha source used for large angle random irradiation. Qualitative images of the energy deposited along the particle tracks have been produced and show good agreement with images of DNA double strand break signalling proteins obtained experimentally. The methodology presented in this paper provides microdosimetric quantities calculated from realistic cellular volumes. It is based on open-source oriented software that is publicly available

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

Autoantibodies against type I IFNs in patients with life-threatening COVID-19

Interindividual clinical variability in the course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is vast. We report that at least 101 of 987 patients with life-threatening coronavirus disease 2019 (COVID-19) pneumonia had neutralizing immunoglobulin G (IgG) autoantibodies (auto-Abs) against interferon-w (IFN-w) (13 patients), against the 13 types of IFN-a (36), or against both (52) at the onset of critical disease; a few also had auto-Abs against the other three type I IFNs. The auto-Abs neutralize the ability of the corresponding type I IFNs to block SARS-CoV-2 infection in vitro. These auto-Abs were not found in 663 individuals with asymptomatic or mild SARS-CoV-2 infection and were present in only 4 of 1227 healthy individuals. Patients with auto-Abs were aged 25 to 87 years and 95 of the 101 were men. A B cell autoimmune phenocopy of inborn errors of type I IFN immunity accounts for life-threatening COVID-19 pneumonia in at least 2.6% of women and 12.5% of men

Vaccine breakthrough hypoxemic COVID-19 pneumonia in patients with auto-Abs neutralizing type I IFNs

Life-threatening `breakthrough' cases of critical COVID-19 are attributed to poor or waning antibody response to the SARS- CoV-2 vaccine in individuals already at risk. Pre-existing autoantibodies (auto-Abs) neutralizing type I IFNs underlie at least 15% of critical COVID-19 pneumonia cases in unvaccinated individuals; however, their contribution to hypoxemic breakthrough cases in vaccinated people remains unknown. Here, we studied a cohort of 48 individuals ( age 20-86 years) who received 2 doses of an mRNA vaccine and developed a breakthrough infection with hypoxemic COVID-19 pneumonia 2 weeks to 4 months later. Antibody levels to the vaccine, neutralization of the virus, and auto- Abs to type I IFNs were measured in the plasma. Forty-two individuals had no known deficiency of B cell immunity and a normal antibody response to the vaccine. Among them, ten (24%) had auto-Abs neutralizing type I IFNs (aged 43-86 years). Eight of these ten patients had auto-Abs neutralizing both IFN-a2 and IFN-., while two neutralized IFN-omega only. No patient neutralized IFN-ss. Seven neutralized 10 ng/mL of type I IFNs, and three 100 pg/mL only. Seven patients neutralized SARS-CoV-2 D614G and the Delta variant (B.1.617.2) efficiently, while one patient neutralized Delta slightly less efficiently. Two of the three patients neutralizing only 100 pg/mL of type I IFNs neutralized both D61G and Delta less efficiently. Despite two mRNA vaccine inoculations and the presence of circulating antibodies capable of neutralizing SARS-CoV-2, auto-Abs neutralizing type I IFNs may underlie a significant proportion of hypoxemic COVID-19 pneumonia cases, highlighting the importance of this particularly vulnerable population

A novel method for the multiplexed target enrichment of MinION next generation sequencing libraries using PCR-generated baits

The enrichment of targeted regions within complex next generation sequencing libraries commonly uses biotinylated baits to capture the desired sequences. This method results in high read coverage over the targets and their flanking regions. Oxford Nanopore Technologies recently released an USB3.0-interfaced sequencer, the MinION. To date no particular method for enriching MinION libraries has been standardized. Here, using biotinylated PCR-generated baits in a novel approach, we describe a simple and efficient way for multiplexed enrichment of MinION libraries, overcoming technical limitations related with the chemistry of the sequencing-adapters and the length of the DNA fragments. Using Phage Lambda and Escherichia coli as models we selectively enrich for specific targets, significantly increasing the corresponding read-coverage, eliminating unwanted regions. We show that by capturing genomic fragments, which contain the target sequences, we recover reads extending targeted regions and thus can be used for the determination of potentially unknown flanking sequences. By pooling enriched libraries derived from two distinct E. coli strains and analyzing them in parallel, we demonstrate the efficiency of this method in multiplexed format. Crucially we evaluated the optimal bait size for large fragment libraries and we describe for the first time a standardized method for target enrichment in MinION platform

Vestibular paroxysmia: Clinical features and imaging findings; a literature review

According to the definition of neurovascular compression syndromes (NVCS), a vascular structure in direct contact with a cranial nerve is causing mechanical irritation of the neural tissue producing correlating symptoms. Vestibular paroxysmia is an example of a neurovascular compression which is caused by neurovascular contact between the eighth cranial nerve and a vessel. It is crucial to understand the unique anatomy of the vestibulocochlear nerve in order to study the syndrome which is the result of its compression. More specifically, the long transitional zone between central and peripheral myelin plays a central role in clinical significance, as the transitional zone is the structure most prone to mechanical injury. Imaging techniques of the eighth cranial nerve and the surrounding structures are substantial for the demonstration of clinically significant cases and potential surgical decompression. The goal of the current review is to present and study the existing literature on vestibular paroxysmia and to search for the most appropriate imaging technique for the syndrome. An extensive literature search of PubMed database was performed, and the studies were ranked based on evidence-based criteria, followed by descriptive statistics of the data. The present analysis indicates that 3D CISS MRI sequence is superior to any other sequence, in the most studies reviewed, regarding the imaging of neurovascular compression of the eighth cranial nerve. © 2021 Elsevier Masson SA