Three-Neutrino Oscillations of Atmospheric Neutrinos, theta13, Neutrino Mass Hierarchy and Iron Magnetized Detectors

We derive predictions for the Nadir angle (theta_n) dependence of the ratio Nmu-/Nmu+ of the rates of the mu- and mu+ multi-GeV events, and for the mu- - mu+ event rate asymmetry, A_{mu-mu+}=[Nmu- - Nmu+]/[Nmu- + Nmu+], in iron-magnetized calorimeter detectors (MINOS, INO) in the case of 3-neutrino oscillations of the atmospheric nu_mu and antinu_mu, driven by one neutrino mass squared difference, |Delta m^2_{31}| >> Delta m^2_{21}. The asymmetry A_{mu- mu+} (the ratio Nmu-/Nmu+) is shown to be particularly sensitive to the Earth matter effects in the atmospheric neutrino oscillations, and thus to the values of sin^2(theta13) and sin^2(theta23), theta13 and theta23 being the neutrino mixing angles limited by the CHOOZ and Palo Verde experiments and that responsible for the dominant atmospheric nu_mu -> nu_tau (antinu_mu -> antinu_tau) oscillations. It is also very sensitive to the type of neutrino mass spectrum which can be with normal (Delta m^2_{31}>0) or with inverted (Delta m^2_{31} 0.50, sin^2(2 theta13)>0.06 and Delta m^2_{31}=(2-3) 10^{-3} eV^2, the Earth matter effects produce a relative difference between the integrated asymmetries barA_{mu- mu+} and barA^{2nu}_{mu- mu+}$ in the mantle (cos(theta_n)=0.30-0.84) and core (cos(theta_n)=0.84-1.0) bins, which is bigger in absolute value than ~15%, can reach the values of (30-35)%, and thus can be sufficiently large to be observable. The sign of the indicated asymmetry difference is anticorrelated with the sign of Delta m^2_{31}. An observation of the Earth matter effects in the Nadir angle distribution of the asymmetry A_{mu- mu+} (ratio Nmu-/Nmu+) would clearly indicate that sin^2(2 theta13)>0.06 and sin^2(theta23)>0.50, and would lead to the determination of the sign of Delta m^2_{31}.Comment: 27 pages, 9 figure

Enhancement of CP Violating terms for Neutrino Oscillation in Earth Matter

We investigate the $\nu_e \to \nu_{\mu}$ oscillation in the framework of three generations when neutrinos pass through the earth. The oscillation probability is represented by the form, $P(\nu_e \to \nu_\mu)=A\cos \delta+B\sin \delta+C$ in arbitrary matter profile by using the leptonic CP phase $\delta$. We compare our approximate formula in the previous paper with the formula which includes second order terms of $\alpha=\Delta m_{21}^2/\Delta m_{31}^2$ and $s_{13}=\sin \theta_{13}$. Non-perturbative effects of $\alpha$ and $s_{13}$ can be taken into account in our formula and the precision of the formula is rather improved around the MSW resonance region. Furthermore, we compare the earth matter effect of $A$ and $B$ with that of $C$ studied by other authors. We show that the magnitude of $A$ and $B$ can reach a few ten % of $C$ around the main three peaks of $C$ in the region $E>1$ GeV by numerical calculation. We give the qualitative understanding of this result by using our approximate formula. The mantle-core effect, which is different from the usual MSW effect, appears not only in $C$ but also in $A$ and $B$, although the effect is weakened.Comment: 16 pages, 5 figure

Atmospheric Neutrino Oscillations, theta(13) and Neutrino Mass Hierarchy

We derive predictions for the Nadir angle (theta(n)) dependence of the ratio N(mu)/N(e) of the rates of the mu-like and e-like multi-GeV events measured in water-Cerenkov detectors in the case of 3-neutrino oscillations of the atmospheric nu(e) (antinu(e)) and nu(mu) (antinu(mu)), driven by one neutrino mass squared difference, |Delta m2(31)| ~ (2.5 - 3.0) x 10^(-3) eV^2 >> Delta m2(21). This ratio is particularly sensitive to the Earth matter effects in the atmospheric neutrino oscillations, and thus to the values of sin^2(theta(13)) and sin^2(theta(23)), theta(13) and theta(23) being the neutrino mixing angle limited by the CHOOZ and Palo Verde experiments and that responsible for the dominant atmospheric nu(mu) -> nu(tau) (antinu(mu) -> antinu(tau)) oscillations. It is also sensitive to the type of neutrino mass spectrum which can be with normal (Delta m2(31) > 0) or with inverted (Delta m2(31) < 0) hierarchy. We show that for sin^2(theta(13)) > 0.01, sin^2(theta(23)) > 0.5 and at cos(theta(n)) > 0.4, the Earth matter effects modify substantially the theta(n)-dependence of the ratio N(mu)/N(e) and in a way which cannot be reproduced with sin^2(theta(13)) = 0 and a different value of sin^2(theta(23)). For normal hierarchy the effects can be as large as ~ 25% for cos(theta(n)) ~ (0.5 - 0.8), can reach ~ 35% in the Earth core bin cos(theta(n)) ~ (0.84 - 1.0), and might be observable. They are typically by ~ 10% smaller in the inverted hierarchy case. An observation of the Earth matter effects in the Nadir angle distribution of the ratio N(mu)/N(e) would clearly indicate that sin^2(theta(13)) > 0.01 and sin^2(theta(23)) > 0.50.Comment: 22 p

Reverse breeding: a novel breeding approach based on engineered meiosis

Reverse breeding (RB) is a novel plant breeding technique designed to directly produce parental lines for any heterozygous plant, one of the most sought after goals in plant breeding. RB generates perfectly complementing homozygous parental lines through engineered meiosis. The method is based on reducing genetic recombination in the selected heterozygote by eliminating meiotic crossing over. Male or female spores obtained from such plants contain combinations of non-recombinant parental chromosomes which can be cultured in vitro to generate homozygous doubled haploid plants (DHs). From these DHs, complementary parents can be selected and used to reconstitute the heterozygote in perpetuity. Since the fixation of unknown heterozygous genotypes is impossible in traditional plant breeding, RB could fundamentally change future plant breeding. In this review, we discuss various other applications of RB, including breeding per chromosome

Functional divergence in the role of N-linked glycosylation in smoothened signaling

The G protein-coupled receptor (GPCR) Smoothened (Smo) is the requisite signal transducer of the evolutionarily conserved Hedgehog (Hh) pathway. Although aspects of Smo signaling are conserved from Drosophila to vertebrates, significant differences have evolved. These include changes in its active sub-cellular localization, and the ability of vertebrate Smo to induce distinct G protein-dependent and independent signals in response to ligand. Whereas the canonical Smo signal to Gli transcriptional effectors occurs in a G protein-independent manner, its non-canonical signal employs Gαi. Whether vertebrate Smo can selectively bias its signal between these routes is not yet known. N-linked glycosylation is a post-translational modification that can influence GPCR trafficking, ligand responsiveness and signal output. Smo proteins in Drosophila and vertebrate systems harbor N-linked glycans, but their role in Smo signaling has not been established. Herein, we present a comprehensive analysis of Drosophila and murine Smo glycosylation that supports a functional divergence in the contribution of N-linked glycans to signaling. Of the seven predicted glycan acceptor sites in Drosophila Smo, one is essential. Loss of N-glycosylation at this site disrupted Smo trafficking and attenuated its signaling capability. In stark contrast, we found that all four predicted N-glycosylation sites on murine Smo were dispensable for proper trafficking, agonist binding and canonical signal induction. However, the under-glycosylated protein was compromised in its ability to induce a non-canonical signal through Gαi, providing for the first time evidence that Smo can bias its signal and that a post-translational modification can impact this process. As such, we postulate a profound shift in N-glycan function from affecting Smo ER exit in flies to influencing its signal output in mice

Comprehensive Analysis of NRG1 Common and Rare Variants in Hirschsprung Patients

Hirschsprung disease (HSCR, OMIM 142623) is a developmental disorder characterized by the absence of ganglion cells along variable lengths of the distal gastrointestinal tract, which results in tonic contraction of the aganglionic gut segment and functional intestinal obstruction. The RET proto-oncogene is the major gene for HSCR with differential contributions of its rare and common, coding and noncoding mutations to the multifactorial nature of this pathology. Many other genes have been described to be associated with the pathology, as NRG1 gene (8p12), encoding neuregulin 1, which is implicated in the development of the enteric nervous system (ENS), and seems to contribute by both common and rare variants. Here we present the results of a comprehensive analysis of the NRG1 gene in the context of the disease in a series of 207 Spanish HSCR patients, by both mutational screening of its coding sequence and evaluation of 3 common tag SNPs as low penetrance susceptibility factors, finding some potentially damaging variants which we have functionally characterized. All of them were found to be associated with a significant reduction of the normal NRG1 protein levels. The fact that those mutations analyzed alter NRG1 protein would suggest that they would be related with HSCR disease not only in Chinese but also in a Caucasian population, which reinforces the implication of NRG1 gene in this pathology

An Influenza A/H1N1/2009 Hemagglutinin Vaccine Produced in Escherichia coli

The A/H1N1/2009 influenza pandemic made evident the need for faster and higher-yield methods for the production of influenza vaccines. Platforms based on virus culture in mammalian or insect cells are currently under investigation. Alternatively, expression of fragments of the hemagglutinin (HA) protein in prokaryotic systems can potentially be the most efficacious strategy for the manufacture of large quantities of influenza vaccine in a short period of time. Despite experimental evidence on the immunogenic potential of HA protein constructs expressed in bacteria, it is still generally accepted that glycosylation should be a requirement for vaccine efficacy.We expressed the globular HA receptor binding domain, referred to here as HA(63-286)-RBD, of the influenza A/H1N1/2009 virus in Escherichia coli using a simple, robust and scalable process. The recombinant protein was refolded and purified from the insoluble fraction of the cellular lysate as a single species. Recombinant HA(63-286)-RBD appears to be properly folded, as shown by analytical ultracentrifugation and bio-recognition assays. It binds specifically to serum antibodies from influenza A/H1N1/2009 patients and was found to be immunogenic, to be capable of triggering the production of neutralizing antibodies, and to have protective activity in the ferret model.Projections based on our production/purification data indicate that this strategy could yield up to half a billion doses of vaccine per month in a medium-scale pharmaceutical production facility equipped for bacterial culture. Also, our findings demonstrate that glycosylation is not a mandatory requirement for influenza vaccine efficacy

Adapting to changes in volcanic behaviour: Formal and informal interactions for enhanced risk management at Tungurahua Volcano, Ecuador

This paper provides an example of how communities can adapt to extreme forms of environmental change and uncertainty over the longer term. We analyse the interactions between scientists, communities and risk managers and examine the interpretation and communication of uncertain scientific information during a long-lived volcanic eruption in Tungurahua, Ecuador. This is complemented with a detailed study of the eruptions of 2006 and 2014, which exemplifies the complexity of interactions during periods of heightened volcanic activity. Our study describes how a ‘shadow network’ has developed outside of, but in interaction with, the formal risk management institutions in Ecuador, improving decision-making in response to heightened volcanic activity. The findings suggest that the interactions have facilitated important adaptations in the scientific advisory response during eruptions (near-real-time interpretation of the volcanic hazards), in hazard communication, and in the evacuation processes. Improved communication between stakeholders and the establishment of thresholds for evacuations have created an effective voluntary evacuation system unique to Tungurahua, allowing people to continue to maintain their livelihoods during heightened volcanic activity and associated periods of uncertainty. Understanding how shadow networks act to minimise the negative consequences of volcanic activity provides valuable insights for increasing societal resilience to other types of hazards

Utility of COVID-19 antigen testing in the emergency department

Background: The BinaxNOW coronavirus disease 2019 (COVID-19) Ag Card test (Abbott Diagnostics Scarborough, Inc.) is a lateral flow immunochromatographic point-of-care test for the qualitative detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) nucleocapsid protein antigen. It provides results from nasal swabs in 15 minutes. Our purpose was to determine its sensitivity and specificity for a COVID-19 diagnosis. Methods: Eligible patients had symptoms of COVID-19 or suspected exposure. After consent, 2 nasal swabs were collected; 1 was tested using the Abbott RealTime SARS-CoV-2 (ie, the gold standard polymerase chain reaction test) and the second run on the BinaxNOW point of care platform by emergency department staff. Results: From July 20 to October 28, 2020, 767 patients were enrolled, of which 735 had evaluable samples. Their mean (SD) age was 46.8 (16.6) years, and 422 (57.4%) were women. A total of 623 (84.8%) patients had COVID-19 symptoms, most commonly shortness of breath (n = 404; 55.0%), cough (n = 314; 42.7%), and fever (n = 253; 34.4%). Although 460 (62.6%) had symptoms ≤7 days, the mean (SD) time since symptom onset was 8.1 (14.0) days. Positive tests occurred in 173 (23.5%) and 141 (19.2%) with the gold standard versus BinaxNOW test, respectively. Those with symptoms \u3e2 weeks had a positive test rate roughly half of those with earlier presentations. In patients with symptoms ≤7 days, the sensitivity, specificity, and negative and positive predictive values for the BinaxNOW test were 84.6%, 98.5%, 94.9%, and 95.2%, respectively. Conclusions: The BinaxNOW point-of-care test has good sensitivity and excellent specificity for the detection of COVID-19. We recommend using the BinasNOW for patients with symptoms up to 2 weeks

Grammatical evolution decision trees for detecting gene-gene interactions

<p>Abstract</p> <p>Background</p> <p>A fundamental goal of human genetics is the discovery of polymorphisms that predict common, complex diseases. It is hypothesized that complex diseases are due to a myriad of factors including environmental exposures and complex genetic risk models, including gene-gene interactions. Such epistatic models present an important analytical challenge, requiring that methods perform not only statistical modeling, but also variable selection to generate testable genetic model hypotheses. This challenge is amplified by recent advances in genotyping technology, as the number of potential predictor variables is rapidly increasing.</p> <p>Methods</p> <p>Decision trees are a highly successful, easily interpretable data-mining method that are typically optimized with a hierarchical model building approach, which limits their potential to identify interacting effects. To overcome this limitation, we utilize evolutionary computation, specifically grammatical evolution, to build decision trees to detect and model gene-gene interactions. In the current study, we introduce the Grammatical Evolution Decision Trees (GEDT) method and software and evaluate this approach on simulated data representing gene-gene interaction models of a range of effect sizes. We compare the performance of the method to a traditional decision tree algorithm and a random search approach and demonstrate the improved performance of the method to detect purely epistatic interactions.</p> <p>Results</p> <p>The results of our simulations demonstrate that GEDT has high power to detect even very moderate genetic risk models. GEDT has high power to detect interactions with and without main effects.</p> <p>Conclusions</p> <p>GEDT, while still in its initial stages of development, is a promising new approach for identifying gene-gene interactions in genetic association studies.</p