180 research outputs found

    Information flows among rivals and corporate investment

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    Using a novel pairwise measure of firms' acquisitions of rivals' disclosures, we show that investment opportunities drive interfirm information flows. We find that these flows predict subsequent mergers and acquisitions as well as how and how much firms invest, relative to rivals. Moreover, firms' use of rivals' information often hinges on the similarities of their products. Our results suggest that rivals' public information, far from being unusable, helps facilitate investment and product decisions, including acquisitions and product differentiation strategies. The findings also support a learning mechanism that could partly underlie the emerging literature on peer investment effects

    I. Flux and color variations of the quadruply imaged quasar HE 0435-1223

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    aims: We present VRi photometric observations of the quadruply imaged quasar HE 0435-1223, carried out with the Danish 1.54m telescope at the La Silla Observatory. Our aim was to monitor and study the magnitudes and colors of each lensed component as a function of time. methods: We monitored the object during two seasons (2008 and 2009) in the VRi spectral bands, and reduced the data with two independent techniques: difference imaging and PSF (Point Spread Function) fitting.results: Between these two seasons, our results show an evident decrease in flux by ~0.2-0.4 magnitudes of the four lensed components in the three filters. We also found a significant increase (~0.05-0.015) in their V-R and R-i color indices. conclusions: These flux and color variations are very likely caused by intrinsic variations of the quasar between the observed epochs. Microlensing effects probably also affect the brightest "A" lensed component.Comment: 10 pages, 8 figure

    Who Watches the Watchmen? An Appraisal of Benchmarks for Multiple Sequence Alignment

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    Multiple sequence alignment (MSA) is a fundamental and ubiquitous technique in bioinformatics used to infer related residues among biological sequences. Thus alignment accuracy is crucial to a vast range of analyses, often in ways difficult to assess in those analyses. To compare the performance of different aligners and help detect systematic errors in alignments, a number of benchmarking strategies have been pursued. Here we present an overview of the main strategies--based on simulation, consistency, protein structure, and phylogeny--and discuss their different advantages and associated risks. We outline a set of desirable characteristics for effective benchmarking, and evaluate each strategy in light of them. We conclude that there is currently no universally applicable means of benchmarking MSA, and that developers and users of alignment tools should base their choice of benchmark depending on the context of application--with a keen awareness of the assumptions underlying each benchmarking strategy.Comment: Revie

    The Dawn of Open Access to Phylogenetic Data

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    The scientific enterprise depends critically on the preservation of and open access to published data. This basic tenet applies acutely to phylogenies (estimates of evolutionary relationships among species). Increasingly, phylogenies are estimated from increasingly large, genome-scale datasets using increasingly complex statistical methods that require increasing levels of expertise and computational investment. Moreover, the resulting phylogenetic data provide an explicit historical perspective that critically informs research in a vast and growing number of scientific disciplines. One such use is the study of changes in rates of lineage diversification (speciation - extinction) through time. As part of a meta-analysis in this area, we sought to collect phylogenetic data (comprising nucleotide sequence alignment and tree files) from 217 studies published in 46 journals over a 13-year period. We document our attempts to procure those data (from online archives and by direct request to corresponding authors), and report results of analyses (using Bayesian logistic regression) to assess the impact of various factors on the success of our efforts. Overall, complete phylogenetic data for ~60% of these studies are effectively lost to science. Our study indicates that phylogenetic data are more likely to be deposited in online archives and/or shared upon request when: (1) the publishing journal has a strong data-sharing policy; (2) the publishing journal has a higher impact factor, and; (3) the data are requested from faculty rather than students. Although the situation appears dire, our analyses suggest that it is far from hopeless: recent initiatives by the scientific community -- including policy changes by journals and funding agencies -- are improving the state of affairs

    Variation in the Analysis of Positively Selected Sites Using Nonsynonymous/Synonymous Rate Ratios: An Example Using Influenza Virus

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    Sites in a gene showing the nonsynonymous/synonymous rate ratio (Ο‰) >1 have been frequently identified to be under positive selection. To examine the performance of such analysis, sites of the Ο‰ ratio >1 in the HA1 gene of H3N2 subtype human influenza viruses were identified from seven overlapping sequence data sets in this study. Our results showed that the sites of the Ο‰ ratio >1 were of significant variation among the data sets even though they targeted similar clusters, indicating that the analysis is likely to be either of low sensitivity or of low specificity in identifying sites under positive selection. Most (43/45) of the sites showing Ο‰ >1 calculated from at least one data set are involved in B-cell epitopes which cover less than a half sites in the protein, suggesting that the analysis is likely to be of low sensitivity rather than of low specificity. It was further found that the analysis sensitivity could not be enhanced by including more sequences or covering longer time intervals. Previously some reports also likely identified only a portion of the sites under positive selection in the viral gene using the Ο‰ ratio. Low sensitivity of the analysis may result from that some sites under positive selection in the gene are also under negative (purifying) selection simultaneously for functional constrains, and so their Ο‰ ratios could be <1. Theoretically, the sites under the two opposite selection forces at the same time favor only certain nonsynonymous changes, e.g. those changing the antigenicity of the gene and maintaining the gene function. This study also suggested that sometimes we can identify more sites under positive selection using the Ο‰ ratio by integrating the positively selected sites estimated from multiple data sets

    Changing Selective Pressure during Antigenic Changes in Human Influenza H3

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    The rapid evolution of influenza viruses presents difficulties in maintaining the optimal efficiency of vaccines. Amino acid substitutions result in antigenic drift, a process whereby antisera raised in response to one virus have reduced effectiveness against future viruses. Interestingly, while amino acid substitutions occur at a relatively constant rate, the antigenic properties of H3 move in a discontinuous, step-wise manner. It is not clear why this punctuated evolution occurs, whether this represents simply the fact that some substitutions affect these properties more than others, or if this is indicative of a changing relationship between the virus and the host. In addition, the role of changing glycosylation of the haemagglutinin in these shifts in antigenic properties is unknown. We analysed the antigenic drift of HA1 from human influenza H3 using a model of sequence change that allows for variation in selective pressure at different locations in the sequence, as well as at different parts of the phylogenetic tree. We detect significant changes in selective pressure that occur preferentially during major changes in antigenic properties. Despite the large increase in glycosylation during the past 40 years, changes in glycosylation did not correlate either with changes in antigenic properties or with significantly more rapid changes in selective pressure. The locations that undergo changes in selective pressure are largely in places undergoing adaptive evolution, in antigenic locations, and in locations or near locations undergoing substitutions that characterise the change in antigenicity of the virus. Our results suggest that the relationship of the virus to the host changes with time, with the shifts in antigenic properties representing changes in this relationship. This suggests that the virus and host immune system are evolving different methods to counter each other. While we are able to characterise the rapid increase in glycosylation of the haemagglutinin during time in human influenza H3, an increase not present in influenza in birds, this increase seems unrelated to the observed changes in antigenic properties

    Glycosylation Focuses Sequence Variation in the Influenza A Virus H1 Hemagglutinin Globular Domain

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    Antigenic drift in the influenza A virus hemagglutinin (HA) is responsible for seasonal reformulation of influenza vaccines. Here, we address an important and largely overlooked issue in antigenic drift: how does the number and location of glycosylation sites affect HA evolution in man? We analyzed the glycosylation status of all full-length H1 subtype HA sequences available in the NCBI influenza database. We devised the β€œflow index” (FI), a simple algorithm that calculates the tendency for viruses to gain or lose consensus glycosylation sites. The FI predicts the predominance of glycosylation states among existing strains. Our analyses show that while the number of glycosylation sites in the HA globular domain does not influence the overall magnitude of variation in defined antigenic regions, variation focuses on those regions unshielded by glycosylation. This supports the conclusion that glycosylation generally shields HA from antibody-mediated neutralization, and implies that fitness costs in accommodating oligosaccharides limit virus escape via HA hyperglycosylation

    A Full Year's Chandra Exposure on SDSS Quasars from the Chandra Multiwavelength Project

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    We study the spectral energy distributions and evolution of a large sample of optically selected quasars from the Sloan Digital Sky Survey (SDSS) that were observed in 323 Chandra images analyzed by the Chandra Multiwavelength Project (ChaMP). Our highest-confidence matched sample includes 1135 X-ray detected quasars in the redshift range 0.2<z<5.4, representing some 36Msec of effective exposure. Spectroscopic redshifts are available for about 1/3 of the detected sample; elsewhere, redshifts are estimated photometrically. With 56 z>3 QSOs detected, we find no evidence for evolution out to z~5 for either the X-ray photon index Gamma or for the ratio of optical/UV to X-ray flux alpha_ox. About 10% of detected QSOs are obscured (Nh>1E22), but the fraction might reach ~1/3 if most non-detections are absorbed. We confirm a significant correlation between alpha_ox and optical luminosity, but it flattens or disappears for fainter AGN alone. Gamma hardens significantly both towards higher X-ray luminosity, and for relatively X-ray loud quasars. These trends may represent a relative increase in non-thermal X-ray emission, and our findings thereby strengthen analogies between Galactic black hole binaries and AGN.Comment: 28 pages, 21 figures. Accepted (26 Aug 2008) for publication in ApJS. Electronic datafiles (for tables 2 and 3) and high resolution figures available at http://hea-www.harvard.edu/CHAMP

    Identifying Changes in Selective Constraints: Host Shifts in Influenza

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    The natural reservoir of Influenza A is waterfowl. Normally, waterfowl viruses are not adapted to infect and spread in the human population. Sometimes, through reassortment or through whole host shift events, genetic material from waterfowl viruses is introduced into the human population causing worldwide pandemics. Identifying which mutations allow viruses from avian origin to spread successfully in the human population is of great importance in predicting and controlling influenza pandemics. Here we describe a novel approach to identify such mutations. We use a sitewise non-homogeneous phylogenetic model that explicitly takes into account differences in the equilibrium frequencies of amino acids in different hosts and locations. We identify 172 amino acid sites with strong support and 518 sites with moderate support of different selection constraints in human and avian viruses. The sites that we identify provide an invaluable resource to experimental virologists studying adaptation of avian flu viruses to the human host. Identification of the sequence changes necessary for host shifts would help us predict the pandemic potential of various strains. The method is of broad applicability to investigating changes in selective constraints when the timing of the changes is known
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