A full analytic solution of SO(10)-inspired leptogenesis

Abstract Recent encouraging experimental results on neutrino mixing parameters prompt further investigation on SO(10)-inspired leptogenesis and on the associated strong thermal solution that has correctly predicted a non-vanishing reactor mixing angle, it further predicts sin δ ≲ 0, now supported by recent results at ∼ 95% C.L., normally ordered neutrino masses and atmospheric mixing angle in the first octant, best fit results in latest global analyses. Extending a recent analytical procedure, we account for the mismatch between the Yukawa basis and the weak basis, that in SO(10)-inspired models is described by a CKM-like unitary transformation V L , obtaining a full analytical solution that provides useful insight and reproduces accurately all numerical results, paving the way for future inclusion of different sources of theoretical uncertainties and for a statistical analysis of the constraints. We show how muon-dominated solutions appear for large values of the lightest neutrino mass in the range (0.01–1) eV but also how they necessarily require a mild fine tuning in the seesaw relation. For the dominant (and untuned) tauon-dominated solutions we show analytically how, turning on V L ≃ V CKM, some of the constraints on the low energy neutrino parameters get significantly relaxed. In particular we show how the upper bound on the atmospheric neutrino mixing angle in the strong thermal solution gets relaxed from θ 23 ≲ 41° to θ 23 ≲ 44°, an important effect in the light of the most recent NOνA, T2K and IceCube results

Why stem/progenitor cells lose their regenerative potential

Nowadays, it is clear that adult stem cells, also called as tissue stem cells, play a central role to repair and maintain the tissue in which they reside by their selfrenewal ability and capacity of differentiating into distinct and specialized cells. As stem cells age, their renewal ability declines and their capacity to maintain organ homeostasis and regeneration is impaired. From a molecular perspective, these changes in stem cells properties can be due to several types of cell intrinsic injury and DNA aberrant alteration (i.e epigenomic profile) as well as changes in the tissue microenviroment, both into the niche and by systemic circulating factors. Strikingly, it has been suggested that aging-induced deterioration of stem cell functions may play a key role in the pathophysiology of the various agingassociated disorders. Therefore, understanding how resident stem cell age and affects near and distant tissues is fundamental. Here, we examine the current knowledge about aging mechanisms in several kinds of adult stem cells under physiological and pathological conditions and the principal aging-related changes in number, function and phenotype that determine the loss of tissue renewal properties. Furthermore, we examine the possible cell rejuvenation strategies. Stem cell rejuvenation may reverse the aging phenotype and the discovery of effective methods for inducing and differentiating pluripotent stem cells for cell replacement therapies could open up new possibilities for treating age-related diseases

Multi-step exploitation of raw arundo donax L. For the selective synthesis of second-generation sugars by chemical and biological route

Lignocellulosic biomass represents one of the most important feedstocks for future biorefineries, being a precursor of valuable bio-products, obtainable through both chemical and biological conversion routes. Lignocellulosic biomass has a complex matrix, which requires the careful development of multi-step approaches for its complete exploitation to value-added compounds. Based on this perspective, the present work focuses on the valorization of hemicellulose and cellulose fractionsof giant reed (Arundo donax L.) to give second-generation sugars, minimizing the formation of reaction by-products. The conversion of hemicellulose to xylose was undertaken in the presence of the heterogeneous acid catalyst Amberlyst-70 under microwave irradiation. The effect of the main reaction parameters, such as temperature, reaction time, catalyst, and biomass loadings on sugars yield was studied, developing a high gravity approach. Under the optimised reaction conditions (17 wt% Arundo donax L. loading, 160 °C, Amberlyst-70/Arundo donax L. weight ratio 0.2 wt/wt), the xylose yield was 96.3 mol%. In the second step, the cellulose-rich solid residue was exploited through the chemical or enzymatic route, obtaining glucose yields of32.5 and56.2 mol%, respectively. This work proves the efficiency of this innovative combination of chemical and biological catalytic approaches, for the selective conversion of hemicellulose and cellulose fractions of Arundo donax L. to versatile platform products

Inhomogeneous Diastereomeric Composition of Mongersen Antisense Phosphorothioate Oligonucleotide Preparations and Related Pharmacological Activity Impairment

Mongersen is a 21-mer antisense oligonucleotide designed to downregulate Mothers against decapentaplegic homolog 7 (SMAD7) expression to treat Crohn's disease. Mongersen was manufactured in numerous batches at different scales during several years of clinical development, which all appeared identical, using common physicochemical analytical techniques, while only phosphorous-31 nuclear magnetic resonance (P-31-NMR) in solution showed marked differences. Close-up analysis of 27 mongersen batches revealed marked differences in SMAD7 downregulation in a cell-based assay. Principal component analysis of P-31-NMR profiles showed strong correlation with SMAD7 downregulation and, therefore, with pharmacological efficacy in vitro. Mongersen contains 20 phosphorothioate (PS) linkages, whose chirality (Rp/Sp) was not controlled during manufacturing. A different diastereomeric composition throughout batches would lead to superimposable analytical data, but to distinct P-31-NMR profiles, as indeed we found. We tentatively suggest that this may be the origin of different biological activity. As similar manifolds are expected for other PS-based oligonucleotides, the protocol described here provides a general method to identify PS chirality issues and a chemometric tool to score each preparation for this elusive feature

Analysis, Design and Implementation of an End-to-End QKD Link

This manuscript discusses the most relevant aspects of the practical implementation of a long-range Quantum Key Distribution (QKD) link with trusted nodes, achieving the highest possible secret key rate generation within the security and system level constraints. To this purpose, we report on recent pilot studies for the measurements of detection efficiency and source photon statistics for validating the calibration facilities (i) at telecom wavelength for realistic quantum backbone implementation through standard telecommunications grade optical fiber, and (ii) for the telecom and VIS-NIR regime. In addition, since there are circumstances when a fiber optical link may not be available, we will also discuss the characterization of a Free Space Optics (FSO) QKD link. Finally, the manuscript also discusses the problem of information reconciliation in Continuous Variable QKD (CV-QKD) scenarios

Severe acute respiratory syndrome coronavirus 2 may exploit human transcription factors involved in retinoic acid and interferon-mediated response: a hypothesis supported by an in silico analysis

The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing coronavirus disease 2019 (COVID-19), resulting in acute respiratory disease, is a worldwide emergency. Because recently it has been found that SARS-CoV is dependent on host transcription factors (TF) to express the viral genes, efforts are required to understand the molecular interplay between virus and host response. By bioinformatic analysis, we investigated human TF that can bind the SARS-CoV-2 sequence and can be involved in viral transcription. In particular, we analysed the key role of TF involved in interferon (IFN) response. We found that several TF could be induced by the IFN antiviral response, specifically some induced by IFN-stimulated gene factor 3 (ISGF3) and by unphosphorylated ISGF3, which were found to promote the transcription of several viral open reading frame. Moreover, we found 22 TF binding sites present only in the sequence of virus infecting humans but not bat coronavirus RaTG13. The 22 TF are involved in IFN, retinoic acid signalling and regulation of transcription by RNA polymerase II, thus facilitating its own replication cycle. This mechanism, by competition, may steal the human TF involved in these processes, explaining SARS-CoV-2's disruption of IFN-I signalling in host cells and the mechanism of the SARS retinoic acid depletion syndrome leading to the cytokine storm. We identified three TF binding sites present exclusively in the Brazilian SARS-CoV-2 P.1 variant that may explain the higher severity of the respiratory syndrome. These data shed light on SARS-CoV-2 dependence from the host transcription machinery associated with IFN response and strengthen our knowledge of the virus's transcription and replicative activity, thus paving the way for new targets for drug design and therapeutic approaches

Active-Sterile neutrino oscillations and BBN+CMBR constraints

We show how active-sterile neutrino oscillations in the early Universe can play an interesting role in explaining the current observations of CMBR anisotropies and light element abundances. We describe different possible phenomenological scenarios in the interpretation of present data and how active-sterile neutrino oscillations can provide a viable theoretical framework.Comment: Some changes, to appear in Phys. Rev.