Linking solar and long baseline terrestrial neutrino experiments

We show that in the framework of three light neutrino species with hierarchical masses and assuming no fine tuning between the entries of the neutrino mass matrix, one can use the solar neutrino data to obtain information on the element $U_{e3}$ of the lepton mixing matrix. Conversely, a measurement of $U_{e3}$ in atmospheric or long baseline accelerator or reactor neutrino experiments would help discriminate between possible oscillation solutions of the solar neutrino problem.Comment: revtex, 4 pages, no figures. Discussion of the LOW solution modified; results unchanged. References adde

Design S-N curves for old Portuguese and French riveted bridges connection based on statistical analyses

Maintenance of ancient road and railway metallic bridges has become a major concern for governmental agencies in the past few decades. Indeed, since the construction of these structures, between the end of the 19th century and the beginning of the 20th century, traffic conditions have evolved, both in weight and frequency. In the purpose to assess the remaining life of old metallic bridges, some critical structural details have been identified and associated to S-N curves in order to be used in damage estimation (using Palmgren-Miner’s rule for cumulative damage, for example). These constructional details are described by design rules of several European and North American standards, such as the Eurocode 3, BS 5400 and AASHTO standards. The particularity of ancient bridges is that hot riveted assemblies, commonly used for their construction, are not represented in most construction standards. Further experiences on the matter by numerous research teams have suggested detail category C71 from the Eurocode 3 as appropriate. In this paper, experimental data from double shear assemblies manufactures from three different metallic ancient bridges is used to identify, through a statistical analysis, the S-N curves that best fit this constructional detail. Portuguese and French puddled iron bridges were considered.The authors of this paper thank the National Society of French Railways and the SciTech - Science and Technology for Competitive and Sustainable Industries, R&D project NORTE-01-0145-FEDER-000022 cofinanced by Programa Operacional Regional do Norte ("NORTE2020"), through Fundo Europeu de Desenvolvimento Regional (FEDER) for their collaboration and support during this research works. The authors also acknowledge the Portuguese Science Foundation (FCT) for the financial support through the post-doctoral grant SFRH/BPD/107825/2015

A Simplest A4 Model for Tri-Bimaximal Neutrino Mixing

We present a see-saw $A_4$ model for Tri-Bimaximal mixing which is based on a very economical flavour symmetry and field content and still possesses all the good features of $A_4$ models. In particular the charged lepton mass hierarchies are determined by the $A_4\times Z_4$ flavour symmetry itself without invoking a Froggatt-Nielsen U(1) symmetry. Tri-Bimaximal mixing is exact in leading order while all the mixing angles receive corrections of the same order in next-to-the-leading approximation. As a consequence the predicted value of $\theta_{13}$ is within the sensitivity of the experiments which will take data in the near future. The light neutrino spectrum, typical of $A_4$ see-saw models, with its phenomenological implications, also including leptoproduction, is studied in detail.Comment: 20 pages, 2 figure

Neutrino Masses and Lepton Flavour Violation in Thick Brane Scenarios

We address the issue of lepton flavour violation and neutrino masses in the ``fat-brane'' paradigm, where flavour changing processes are suppressed by localising different fermion field wave-functions at different positions (in the extra dimensions) in a thick brane. We study the consequences of suppressing lepton number violating charged lepton decays within this scenario for lepton masses and mixing angles. In particular, we find that charged lepton mass matrices are constrained to be quasi-diagonal. We further consider whether the same paradigm can be used to naturally explain small Dirac neutrino masses by considering the existence of three right-handed neutrinos in the brane, and discuss the requirements to obtain phenomenologically viable neutrino masses and mixing angles. Finally, we examine models where neutrinos obtain a small Majorana mass by breaking lepton number in a far away brane and show that, if the fat-brane paradigm is the solution to the absence of lepton number violating charged lepton decays, such models predict, in the absence of flavour symmetries, that charged lepton flavour violation will be observed in the next round of rare muon/tau decay experiments.Comment: 33 pages, 9 eps figure

Minimal Scenarios for Leptogenesis and CP Violation

The relation between leptogenesis and CP violation at low energies is analyzed in detail in the framework of the minimal seesaw mechanism. Working, without loss of generality, in a weak basis where both the charged lepton and the right-handed Majorana mass matrices are diagonal and real, we consider a convenient generic parametrization of the Dirac neutrino Yukawa coupling matrix and identify the necessary condition which has to be satisfied in order to establish a direct link between leptogenesis and CP violation at low energies. In the context of the LMA solution of the solar neutrino problem, we present minimal scenarios which allow for the full determination of the cosmological baryon asymmetry and the strength of CP violation in neutrino oscillations. Some specific realizations of these minimal scenarios are considered. The question of the relative sign between the baryon asymmetry and CP violation at low energies is also discussed.Comment: 36 pages, 5 figures; minor corrections and references updated. Final version to appear in Phys. Rev.

Global update on the susceptibility of humam influenza viruses to neuraminidase inhibitors 2012-2013

Emergence of influenza viruses with reduced susceptibility to neuraminidase inhibitors (NAIs) is sporadic, often follows exposure to NAIs, but occasionally occurs in the absence of NAI pressure. The emergence and global spread in 2007/2008 of A(H1N1) influenza viruses showing clinical resistance to oseltamivir due to neuraminidase (NA) H275Y substitution, in the absence of drug pressure, warrants continued vigilance and monitoring for similar viruses. Four World Health Organization (WHO) Collaborating Centres for Reference and Research on Influenza and one WHO Collaborating Centre for the Surveillance, Epidemiology and Control of Influenza (WHO CCs) tested 11,387 viruses collected by WHO-recognized National Influenza Centres (NIC) between May 2012 and May 2013 to determine 50% inhibitory concentration (IC50) data for oseltamivir, zanamivir, peramivir and laninamivir. The data were evaluated using normalized IC50 fold-changes rather than raw IC50 data. Nearly 90% of the 11,387 viruses were from three WHO regions: Western Pacific, the Americas and Europe. Only 0.2% (n=27) showed highly reduced inhibition (HRI) against at least one of the four NAIs, usually oseltamivir, while 0.3% (n=39) showed reduced inhibition (RI). NA sequence data, available from the WHO CCs and from sequence databases (n=3661), were screened for amino acid substitutions associated with reduced NAI susceptibility. Those showing HRI were A(H1N1)pdm09 with NA H275Y (n=18), A(H3N2) with NA E119V (n=3) or NA R292K (n=1) and B/Victoria-lineage with NA H273Y (n=2); amino acid position numbering is A subtype and B type specific. Overall, approximately 99% of circulating viruses tested during the 2012-2013 period were sensitive to all four NAIs. Consequently, these drugs remain an appropriate choice for the treatment and prophylaxis of influenza virus infections

Multiplex PCR for detection of plasmid-mediated colistin resistance determinants, mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5 for surveillance purposes

Background and aim: Plasmid-mediated colistin resistance mechanisms have been identified worldwide in the past years. A multiplex polymerase chain reaction (PCR) protocol for detection of all currently known transferable colistin resistance genes (mcr-1 to mcr-5, and variants) in Enterobacteriaceae was developed for surveillance or research purposes. Methods: We designed four new primer pairs to amplify mcr-1, mcr-2, mcr-3 and mcr-4 gene products and used the originally described primers for mcr-5 to obtain a stepwise separation of ca 200 bp between ampli-cons. The primer pairs and amplification conditions allow for single or multiple detection of all currently described mcr genes and their variants present in Enterobacteriaceae. The protocol was validated testing 49 European Escherichia coli and Salmonella isolates of animal origin. Results: Multiplex PCR results in bovine and porcine isolates from Spain, Germany, France and Italy showed full concordance with whole genome sequence data. The method was able to detect mcr-1, mcr-3 and mcr-4 as singletons or in different combinations as they were present in the test isolates. One new mcr-4 variant, mcr-4.3, was also identified. Conclusions: This method allows rapid identification of mcr-positive bacteria and overcomes the challenges of phenotypic detection of colistin resistance. The multiplex PCR should be particularly interesting in settings or laboratories with limited resources for performing genetic analysis as it provides information on the mechanism of colistin resistance without requiring genome sequencing. © 2018, European Centre for Disease Prevention and Control (ECDC). All rights reserved

Proximity-Induced Nucleic Acid Degrader (PINAD) approach to targeted RNA degradation using small molecules

Nature has evolved intricate machinery to target and degrade RNA, and some of these molecular mechanisms can be adapted for therapeutic use. Small interfering RNAs and RNase H-inducing oligonucleotides have yielded therapeutic agents against diseases that cannot be tackled using protein-centered approaches. Because these therapeutic agents are nucleic acid-based, they have several inherent drawbacks which include poor cellular uptake and stability. Here we report a new approach to target and degrade RNA using small molecules, proximity-induced nucleic acid degrader (PINAD). We have utilized this strategy to design two families of RNA degraders which target two different RNA structures within the genome of SARS-CoV-2: G-quadruplexes and the betacoronaviral pseudoknot. We demonstrate that these novel molecules degrade their targets using in vitro, in cellulo, and in vivo SARS-CoV-2 infection models. Our strategy allows any RNA binding small molecule to be converted into a degrader, empowering RNA binders that are not potent enough to exert a phenotypic effect on their own. PINAD raises the possibility of targeting and destroying any disease-related RNA species, which can greatly expand the space of druggable targets and diseases.info:eu-repo/semantics/publishedVersio

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes