A dimensionless number for understanding the evolutionary dynamics of antigenically variable RNA viruses.

Antigenically variable RNA viruses are significant contributors to the burden of infectious disease worldwide. One reason for their ubiquity is their ability to escape herd immunity through rapid antigenic evolution and thereby to reinfect previously infected hosts. However, the ways in which these viruses evolve antigenically are highly diverse. Some have only limited diversity in the long-run, with every emergence of a new antigenic variant coupled with a replacement of the older variant. Other viruses rapidly accumulate antigenic diversity over time. Others still exhibit dynamics that can be considered evolutionary intermediates between these two extremes. Here, we present a theoretical framework that aims to understand these differences in evolutionary patterns by considering a virus's epidemiological dynamics in a given host population. Our framework, based on a dimensionless number, probabilistically anticipates patterns of viral antigenic diversification and thereby quantifies a virus's evolutionary potential. It is therefore similar in spirit to the basic reproduction number, the well-known dimensionless number which quantifies a pathogen's reproductive potential. We further outline how our theoretical framework can be applied to empirical viral systems, using influenza A/H3N2 as a case study. We end with predictions of our framework and work that remains to be done to further integrate viral evolutionary dynamics with disease ecology

Rich methane laminar flames doped with light unsaturated hydrocarbons. Part II: 1,3butadiene

In line with the study presented in the part I of this paper, the structure of a laminar rich premixed methane flame doped with 1,3-butadiene has been investigated. The flame contains 20.7% (molar) of methane, 31.4% of oxygen and 3.3% of 1,3-butadiene, corresponding to an equivalence ratio of 1.8, and a ratio C4H6 / CH4 of 16 %. The flame has been stabilized on a burner at a pressure of 6.7 kPa using argon as dilutant, with a gas velocity at the burner of 36 cm/s at 333 K. The temperature ranged from 600 K close to the burner up to 2150 K. Quantified species included usual methane C0-C2 combustion products and 1,3-butadiene, but also propyne, allene, propene, propane, 1,2-butadiene, butynes, vinylacetylene, diacetylene, 1,3-pentadiene, 2-methyl-1,3-butadiene (isoprene), 1-pentene, 3-methyl-1-butene, benzene and toluene. In order to model these new results, some improvements have been made to a mechanism previously developed in our laboratory for the reactions of C3-C4 unsaturated hydrocarbons. The main reaction pathways of consumption of 1,3-butadiene and of formation of C6 aromatic species have been derived from flow rate analyses. In this case, the C4 route to benzene formation plays an important role in comparison to the C3 pathway

Genome-wide association study in obsessive-compulsive disorder: results from the OCGAS.

Obsessive-compulsive disorder (OCD) is a psychiatric condition characterized by intrusive thoughts and urges and repetitive, intentional behaviors that cause significant distress and impair functioning. The OCD Collaborative Genetics Association Study (OCGAS) is comprised of comprehensively assessed OCD patients with an early age of OCD onset. After application of a stringent quality control protocol, a total of 1065 families (containing 1406 patients with OCD), combined with population-based samples (resulting in a total sample of 5061 individuals), were studied. An integrative analyses pipeline was utilized, involving association testing at single-nucleotide polymorphism (SNP) and gene levels (via a hybrid approach that allowed for combined analyses of the family- and population-based data). The smallest P-value was observed for a marker on chromosome 9 (near PTPRD, P=4.13 × 10(-)(7)). Pre-synaptic PTPRD promotes the differentiation of glutamatergic synapses and interacts with SLITRK3. Together, both proteins selectively regulate the development of inhibitory GABAergic synapses. Although no SNPs were identified as associated with OCD at genome-wide significance level, follow-up analyses of genome-wide association study (GWAS) signals from a previously published OCD study identified significant enrichment (P=0.0176). Secondary analyses of high-confidence interaction partners of DLGAP1 and GRIK2 (both showing evidence for association in our follow-up and the original GWAS study) revealed a trend of association (P=0.075) for a set of genes such as NEUROD6, SV2A, GRIA4, SLC1A2 and PTPRD. Analyses at the gene level revealed association of IQCK and C16orf88 (both P<1 × 10(-)(6), experiment-wide significant), as well as OFCC1 (P=6.29 × 10(-)(5)). The suggestive findings in this study await replication in larger samples

The effect of feedback on the emission properties of the Warm-Hot Intergalactic Medium

At present, 30-40 per cent of the baryons in the local Universe is still undetected. According to theoretical predictions, this gas should reside in filaments filling the large-scale structure (LSS) in the form of a Warm-Hot Intergalactic Medium (WHIM), at temperatures of 10^5 - 10^7 K, thus emitting in the soft X-ray energies via free-free interaction and line emission from heavy elements. In this work we characterize the properties of the X-ray emission of the WHIM, and the LSS in general, focusing on the influence of different physical mechanisms, namely galactic winds (GWs), black-hole feedback and star-formation, and providing estimates of possible observational constraints. To this purpose we use a set of cosmological hydrodynamical simulations that include a self-consistent treatment of star-formation and chemical enrichment of the intergalactic medium, that allows us to follow the evolution of different metal species. We construct a set of simulated light-cones to make predictions of the emission in the 0.3-10 keV energy range. We obtain that GWs increase by a factor of 2 the emission of both galaxy clusters and WHIM. The amount of oxygen at average temperature and, consequently, the amount of expected bright Ovii and Oviii lines is increased by a factor of 3 due to GWs and by 20 per cent when assuming a top-heavy IMF. We compare our results with current observational constraints and find that the emission from faint groups and WHIM should account from half to all of the unresolved X-ray background in the 1-2 keV band.Comment: 15 pages, 8 figures, 4 tables. Accepted for publication in the MNRAS. Minor changes after referee repor

Seyfert's Sextet: where is the gas?

Seyfert's Sextet (a.k.a HCG 79) is one of the most compact and isolated galaxy groups in the local Universe. It shows a prominent diffuse light component that accounts for ~50% of the total observed light. This likely indicates that the group is in an advanced evolutionary phase, which would predict a significant hot gaseous component. Previous X-ray observations had suggested a low luminosity for this system, but with large uncertainties and poor resolution. We present the results from a deep (70 ks), high resolution Chandra observation of Seyfert's Sextet, requested with the aim of separating the X-ray emission associated with the individual galaxies from that of a more extended inter-galactic component. We discuss the spatial and spectral characteristics of this group we derive with those of a few similar systems also studied in the X-ray band. The high resolution X-ray image indicates that the majority of the detected emission does not arise in the compact group but is concentrated towards the NW and corresponds to what appears to be a background galaxy cluster. The emission from the group alone has a total luminosity of ~1x10^40 erg/s in the (0.5-5) keV band. Most of the luminosity can be attributed to the individual sources in the galaxies, and only ~2x10^39 erg/s is due to a gaseous component. However, we find that this component is also mostly associated with the individual galaxies of the Sextet, leaving little or no residual in a truly IGM component. The extremely low luminosity of the diffuse emission in Seyfert's Sextet might be related to its small total mass.Comment: 8 pages, 7 figures. Accepted on A&

Kerr-CFT From Black-Hole Thermodynamics

We analyze the near-horizon limit of a general black hole with two commuting killing vector fields in the limit of zero temperature. We use black hole thermodynamics methods to relate asymptotic charges of the complete spacetime to those obtained in the near-horizon limit. We then show that some diffeomorphisms do alter asymptotic charges of the full spacetime, even though they are defined in the near horizon limit and, therefore, count black hole states. We show that these conditions are essentially the same as considered in the Kerr/CFT corresponcence. From the algebra constructed from these diffeomorphisms, one can extract its central charge and then obtain the black hole entropy by use of Cardy's formula.Comment: 19 pages, JHEP3, no figures. V2: References added, small typos fixe

A Comparative Study of the Formation of Aromatics in Rich Methane Flames Doped by Unsaturated Compounds

For a better modeling of the importance of the different channels leading to the first aromatic ring, we have compared the structures of laminar rich premixed methane flames doped with several unsaturated hydrocarbons: allene and propyne, because they are precursors of propargyl radicals which are well known as having an important role in forming benzene, 1,3-butadiene to put in evidence a possible production of benzene due to reactions of C4 compounds, and, finally, cyclopentene which is a source of cyclopentadienylmethylene radicals which in turn are expected to easily isomerizes to give benzene. These flames have been stabilized on a burner at a pressure of 6.7 kPa (50 Torr) using argon as dilutant, for equivalence ratios (?) from 1.55 to 1.79. A unique mechanism, including the formation and decomposition of benzene and toluene, has been used to model the oxidation of allene, propyne, 1,3 butadiene and cyclopentene. The main reaction pathways of aromatics formation have been derived from reaction rate and sensitivity analyses and have been compared for the three types of additives. These combined analyses and comparisons can only been performed when a unique mechanism is available for all the studied additives

Cancer and thrombosis: Managing the risks and approaches to thromboprophylaxis

Patients with cancer are at increased risk of venous thromboembolism (VTE) compared with patients without cancer. This results from both the prothrombotic effects of the cancer itself and iatrogenic factors, such as chemotherapy, radiotherapy, indwelling central venous devices and surgery, that further increase the risk of VTE. Although cancer-associated thrombosis remains an important cause of morbidity and mortality, it is often underdiagnosed and undertreated. However, evidence is accumulating to support the use of low-molecular-weight heparins (LMWHs) in the secondary prevention of VTE in patients with cancer. Not only have LMWHs been shown to be at least as effective as coumarin derivatives in this setting, but they have a lower incidence of complications, including bleeding, and are not associated with the practical problems of warfarin therapy. Furthermore, a growing number of studies indicate that LMWHs may improve survival among patients with cancer due to a possible antitumor effect. Current evidence suggests that LMWHs should increasingly be considered for the long-term management of VTE in patients with cancer

Adventitious rooting declines with the vegetative to reproductive switch and involves a changed auxin homeostasis

Adventitious rooting, whereby roots form from non-root tissues, is critical to the forestry and horticultural industries that depend on propagating plants from cuttings. A major problem is that age of the tissue affects the ability of the cutting to form adventitious roots. Here, a model system has been developed using Pisum sativum to differentiate between different interpretations of ageing. It is shown that the decline in adventitious rooting is linked to the ontogenetic switch from vegetative to floral and is mainly attributed to the cutting base. Using rms mutants it is demonstrated that the decline is not a result of increased strigolactones inhibiting adventitious root formation. Monitoring endogenous levels of a range of other hormones including a range of cytokinins in the rooting zone revealed that a peak in jasmonic acid is delayed in cuttings from floral plants. Additionally, there is an early peak in indole-3-acetic acid levels 6h post excision in cuttings from vegetative plants, which is absent in cuttings from floral plants. These results were confirmed using DR5:GUS expression. Exogenous supplementation of young cuttings with either jasmonic acid or indole-3-acetic acid promoted adventitious rooting, but neither of these hormones was able to promote adventitious rooting in mature cuttings. DR5:GUS expression was observed to increase in juvenile cuttings with increasing auxin treatment but not in the mature cuttings. Therefore, it seems the vegetative to floral ontogenetic switch involves an alteration in the tissue’s auxin homeostasis that significantly reduces the indole-3-acetic acid pool and ultimately results in a decline in adventitious root formation

Wolbachia and DNA barcoding insects: patterns, potential and problems

Wolbachia is a genus of bacterial endosymbionts that impacts the breeding systems of their hosts. Wolbachia can confuse the patterns of mitochondrial variation, including DNA barcodes, because it influences the pathways through which mitochondria are inherited. We examined the extent to which these endosymbionts are detected in routine DNA barcoding, assessed their impact upon the insect sequence divergence and identification accuracy, and considered the variation present in Wolbachia COI. Using both standard PCR assays (Wolbachia surface coding protein – wsp), and bacterial COI fragments we found evidence of Wolbachia in insect total genomic extracts created for DNA barcoding library construction. When >2 million insect COI trace files were examined on the Barcode of Life Datasystem (BOLD) Wolbachia COI was present in 0.16% of the cases. It is possible to generate Wolbachia COI using standard insect primers; however, that amplicon was never confused with the COI of the host. Wolbachia alleles recovered were predominantly Supergroup A and were broadly distributed geographically and phylogenetically. We conclude that the presence of the Wolbachia DNA in total genomic extracts made from insects is unlikely to compromise the accuracy of the DNA barcode library; in fact, the ability to query this DNA library (the database and the extracts) for endosymbionts is one of the ancillary benefits of such a large scale endeavor – for which we provide several examples. It is our conclusion that regular assays for Wolbachia presence and type can, and should, be adopted by large scale insect barcoding initiatives. While COI is one of the five multi-locus sequence typing (MLST) genes used for categorizing Wolbachia, there is limited overlap with the eukaryotic DNA barcode region