New Technologies for Weather Accident Prevention

Weather is a causal factor in thirty percent of all aviation accidents. Many of these accidents are due to a lack of weather situation awareness by pilots in flight. Improving the strategic and tactical weather information available and its presentation to pilots in flight can enhance weather situation awareness and enable avoidance of adverse conditions. This paper presents technologies for airborne detection, dissemination and display of weather information developed by the National Aeronautics and Space Administration (NASA) in partnership with the Federal Aviation Administration (FAA), National Oceanic and Atmospheric Administration (NOAA), industry and the research community. These technologies, currently in the initial stages of implementation by industry, will provide more precise and timely knowledge of the weather and enable pilots in flight to make decisions that result in safer and more efficient operations

Prediction, dynamics, and visualization of antigenic phenotypes of seasonal influenza viruses

Human seasonal influenza viruses evolve rapidly, enabling the virus population to evade immunity and reinfect previously infected individuals. Antigenic properties are largely determined by the surface glycoprotein hemagglutinin (HA), and amino acid substitutions at exposed epitope sites in HA mediate loss of recognition by antibodies. Here, we show that antigenic differences measured through serological assay data are well described by a sum of antigenic changes along the path connecting viruses in a phylogenetic tree. This mapping onto the tree allows prediction of antigenicity from HA sequence data alone. The mapping can further be used to make predictions about the makeup of the future A(H3N2) seasonal influenza virus population, and we compare predictions between models with serological and sequence data. To make timely model output readily available, we developed a web browser-based application that visualizes antigenic data on a continuously updated phylogeny

Oseltamivir-resistant influenza A(H1N1)pdm09 virus in Dutch travellers returning from Spain, August 2012

Two Dutch travellers were infected with oseltamivirresistant influenza A(H1N1)pdm09 viruses with an H275Y neuraminidase substitution in early August 2012. Both cases were probably infected during separate holidays at the Catalonian coast (Spain). No epidemiological connection between the two cases was found, and neither of them was treated with oseltamivir before specimen collection. Genetic analysis of the neuraminidase gene revealed the presence of previously described permissive mutations that may increase the likelihood of such strains emerging and spreading widely

Identifying the genetic basis of antigenic change in influenza A(H1N1)

Determining phenotype from genetic data is a fundamental challenge. Influenza A viruses undergo rapid antigenic drift and identification of emerging antigenic variants is critical to the vaccine selection process. Using former seasonal influenza A(H1N1) viruses, hemagglutinin sequence and corresponding antigenic data were analyzed in combination with 3-D structural information. We attributed variation in hemagglutination inhibition to individual amino acid substitutions and quantified their antigenic impact, validating a subset experimentally using reverse genetics. Substitutions identified as low-impact were shown to be a critical component of influenza antigenic evolution and by including these, as well as the high-impact substitutions often focused on, the accuracy of predicting antigenic phenotypes of emerging viruses from genotype was doubled. The ability to quantify the phenotypic impact of specific amino acid substitutions should help refine techniques that predict the fitness and evolutionary success of variant viruses, leading to stronger theoretical foundations for selection of candidate vaccine viruses

Multi-Messenger Gravitational Wave Searches with Pulsar Timing Arrays: Application to 3C66B Using the NANOGrav 11-year Data Set

When galaxies merge, the supermassive black holes in their centers may form binaries and, during the process of merger, emit low-frequency gravitational radiation in the process. In this paper we consider the galaxy 3C66B, which was used as the target of the first multi-messenger search for gravitational waves. Due to the observed periodicities present in the photometric and astrometric data of the source of the source, it has been theorized to contain a supermassive black hole binary. Its apparent 1.05-year orbital period would place the gravitational wave emission directly in the pulsar timing band. Since the first pulsar timing array study of 3C66B, revised models of the source have been published, and timing array sensitivities and techniques have improved dramatically. With these advances, we further constrain the chirp mass of the potential supermassive black hole binary in 3C66B to less than $(1.65\pm0.02) \times 10^9~{M_\odot}$ using data from the NANOGrav 11-year data set. This upper limit provides a factor of 1.6 improvement over previous limits, and a factor of 4.3 over the first search done. Nevertheless, the most recent orbital model for the source is still consistent with our limit from pulsar timing array data. In addition, we are able to quantify the improvement made by the inclusion of source properties gleaned from electromagnetic data to `blind' pulsar timing array searches. With these methods, it is apparent that it is not necessary to obtain exact a priori knowledge of the period of a binary to gain meaningful astrophysical inferences.Comment: 14 pages, 6 figures. Accepted by Ap

Comparative genomics of Cluster O mycobacteriophages

Mycobacteriophages - viruses of mycobacterial hosts - are genetically diverse but morphologically are all classified in the Caudovirales with double-stranded DNA and tails. We describe here a group of five closely related mycobacteriophages - Corndog, Catdawg, Dylan, Firecracker, and YungJamal - designated as Cluster O with long flexible tails but with unusual prolate capsids. Proteomic analysis of phage Corndog particles, Catdawg particles, and Corndog-infected cells confirms expression of half of the predicted gene products and indicates a non-canonical mechanism for translation of the Corndog tape measure protein. Bioinformatic analysis identifies 8-9 strongly predicted SigA promoters and all five Cluster O genomes contain more than 30 copies of a 17 bp repeat sequence with dyad symmetry located throughout the genomes. Comparison of the Cluster O phages provides insights into phage genome evolution including the processes of gene flux by horizontal genetic exchange

Genome-wide evolutionary dynamics of influenza B viruses on a global scale

The global-scale epidemiology and genome-wide evolutionary dynamics of influenza B remain poorly understood compared with influenza A viruses. We compiled a spatio-temporally comprehensive dataset of influenza B viruses, comprising over 2,500 genomes sampled worldwide between 1987 and 2015, including 382 newly-sequenced genomes that fill substantial gaps in previous molecular surveillance studies. Our contributed data increase the number of available influenza B virus genomes in Europe, Africa and Central Asia, improving the global context to study influenza B viruses. We reveal Yamagata-lineage diversity results from co-circulation of two antigenically-distinct groups that also segregate genetically across the entire genome, without evidence of intra-lineage reassortment. In contrast, Victoria-lineage diversity stems from geographic segregation of different genetic clades, with variability in the degree of geographic spread among clades. Differences between the lineages are reflected in their antigenic dynamics, as Yamagata-lineage viruses show alternating dominance between antigenic groups, while Victoria-lineage viruses show antigenic drift of a single lineage. Structural mapping of amino acid substitutions on trunk branches of influenza B gene phylogenies further supports these antigenic differences and highlights two potential mechanisms of adaptation for polymerase activity. Our study provides new insights into the epidemiological and molecular processes shaping influenza B virus evolution globally

Global circulation patterns of seasonal influenza viruses vary with antigenic drift.

Understanding the spatiotemporal patterns of emergence and circulation of new human seasonal influenza virus variants is a key scientific and public health challenge. The global circulation patterns of influenza A/H3N2 viruses are well characterized, but the patterns of A/H1N1 and B viruses have remained largely unexplored. Here we show that the global circulation patterns of A/H1N1 (up to 2009), B/Victoria, and B/Yamagata viruses differ substantially from those of A/H3N2 viruses, on the basis of analyses of 9,604 haemagglutinin sequences of human seasonal influenza viruses from 2000 to 2012. Whereas genetic variants of A/H3N2 viruses did not persist locally between epidemics and were reseeded from East and Southeast Asia, genetic variants of A/H1N1 and B viruses persisted across several seasons and exhibited complex global dynamics with East and Southeast Asia playing a limited role in disseminating new variants. The less frequent global movement of influenza A/H1N1 and B viruses coincided with slower rates of antigenic evolution, lower ages of infection, and smaller, less frequent epidemics compared to A/H3N2 viruses. Detailed epidemic models support differences in age of infection, combined with the less frequent travel of children, as probable drivers of the differences in the patterns of global circulation, suggesting a complex interaction between virus evolution, epidemiology, and human behaviour.T.B. was supported by a Newton International Fellowship from the Royal Society and through NIH U54 GM111274. S.R. was supported by MRC (UK, Project MR/J008761/1), Wellcome Trust (UK, Project 093488/Z/10/Z), Fogarty International Centre (USA, R01 TW008246‐01), DHS (USA, RAPIDD program), NIGMS (USA, MIDAS U01 GM110721‐01) and NIHR (UK, Health Protection Research Unit funding). The Melbourne WHO Collaborating Centre for Reference and Research on Influenza was supported by the Australian Government Department of Health and thanks N. Komadina and Y.‐M. Deng. The Atlanta WHO Collaborating Center for Surveillance, Epidemiology and Control of Influenza was supported by the U.S. Department of 13 Health and Human Services. NIV thanks A.C. Mishra, M. Chawla‐Sarkar, A.M. Abraham, D. Biswas, S. Shrikhande, AnuKumar B, and A. Jain. Influenza surveillance in India was expanded, in part, through US Cooperative Agreements (5U50C1024407 and U51IP000333) and by the Indian Council of Medical Research. M.A.S. was supported through NSF DMS 1264153 and NIH R01 AI 107034. Work of the WHO Collaborating Centre for Reference and Research on Influenza at the MRC National Institute for Medical Research was supported by U117512723. P.L., A.R. & M.A.S were supported by EU Seventh Framework Programme [FP7/2007‐2013] under Grant Agreement no. 278433-­‐PREDEMICS and ERC Grant agreement no. 260864. C.A.R. was supported by a University Research Fellowship from the Royal Society.This is the author accepted manuscript. It is currently under infinite embargo pending publication of the final version